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Endocrine System

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DOI: 10.1007/978-3-319-47829-6_483-1

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E

Endocrine System functions viz. growth, repair, reproduction, hun-

ger, and survival behavior.
Ashutosh Kumar1,3, Chiman Kumari2,
Sankat Mochan3, Maheswari Kulandhasamy4,
Kishore Sesham3 and Vivek K. Sharma5,6 Introduction
1
Department of Anatomy, All India Institute of
Medical Sciences (AIIMS), Patna, India Animal body has the ductless glands as the dis-
2
Department of Anatomy, Postgraduate Institute tinct organs or cell groups inside an organ or a
of Medical Education & Research (PGIMER), tissue, which exit their secretions called “hor-
Chandigarh, India mones” in the blood circulation to carry to the
3
Department of Anatomy, All India Institute of target destinations. Hormones are involved in the
Medical Sciences (AIIMS), New Delhi, India maintenance of physiological functions involved
4
Department of Biochemistry, Maulana Azad in day to day activities like sleep, feeding, and
Medical College (MAMC), New Delhi, India drinking etc., and also that with prolonged course
5
Department of Physiology, Government Institute of effects like reproduction, growth, aging, immu-
of Medical Sciences (GIMS), Greater Noida, nity, etc. (Kovacs and Ojeda 2012, pp. 1–3).
UP, India These hormone secreting glands are called
6
Department of Physiology, Jawaharlal Institute “endocrine” which literally meant “to secrete
of Postgraduate Medical Education and Research within” indicating their mode of secretion. The
(JIPMER), Pondicherry, India target destinations of the hormones bear the spe-
cific receptors which upon binding induce signal-
ing pathways involved in specific biological
functions. There are eight such major along with
Definition
many minor glands which are grossly conserved
in animal kingdom (including human) and share
It is a physiological functionary comprising of a
similar morphology among mammals. Figure 1 is
network of the ductless glands in the animal body
showing a schema of the major endocrine glands
secreting a chemical messenger, called hormones,
in male and female.
into blood circulation to carry to the target desti-
In general, the “endocrine system” comprises
nations, i.e., various organs and tissues/cells. Hor-
of three parts: a brain part – a nuclei of the hypo-
mones act through the specific receptors
thalamus, a pituitary gland part, and a target endo-
expressed at the target destinations inducing sig-
crine gland. Hypothalamic nuclei secrete
naling pathways involved in the crucial biological
releasing or inhibitory hormones, which either
# Springer International Publishing AG, part of Springer Nature 2018
J. Vonk, T. K. Shackelford (eds.), Encyclopedia of Animal Cognition and Behavior,
https://doi.org/10.1007/978-3-319-47829-6_483-1
2 Endocrine System

Pineal to provide the readers a comprehensive view of

Pituitary the animal “endocrine system,” with a focus in
human.
Thyroid
Thymus

History: A Brief Chronological

Adrenal
Description of the Progress Made in
Pancreas Endocrinology

Earliest descriptions for the endocrine system are

Ovary (female) found about 200 B.C. when Chinese began isolat-
ing sex and pituitary hormones from human urine
and using them for medicinal purposes. Later
Testis (male) descriptions are from the medieval Persia by Avi-
cenna, a legendary scientist, who provided a
detailed account on diabetes mellitus in “The
Canon of Medicine” (c. 1025), describing its clin-
Endocrine System, Fig. 1 Major endocrine glands in the ical features as abnormal appetite, collapse of
human body
sexual functions, and sweet taste of urine.
In 1835 Irish doctor Robert James Graves
stimulate or inhibit anterior pituitary cells to
described a case of goiter with bulging eyes
secrete a stimulatory hormone, which will further
(exophthalmos); the condition was later named
act upon a target endocrine gland like adrenal,
after him as Graves’ disease.
thyroid, or else, which secrete exit hormone
In 1849, Thomas Addison described Addison’s
(s) which will be taken through the blood circula-
disease (also known as primary adrenal deficiency
tion to the target organs or body parts containing
or hypocortisolism). In the same year, Arnold
specific hormonal receptors for action. Exceptions
Berthold, who is regarded as a pioneer in endo-
to this three tier system are some specific cells
crinology, observed that castration had negative
existing inside some organs, or body parts which
effect on male cockerels who did not develop
secrete specific hormones (Kleine and
proper sex-specific characteristics. Later, in 1889
Rossmanith 2016, pp. 269–297; Kumar
Brown-Séquard, a professor at the College de
et al. 2018).
France, reported that self-administration of animal
The endocrine system works in concert with
testes extracts led to enhancements in his physical
the nervous and immune systems which also share
strength, intellectual capacity, and sexual potency
their functionaries (Kovacs and Ojeda 2012,
though it could not be replicated by the others. It
pp. 1–3). The branch of science dealing with the
could not be clarified further until 1904, the year
endocrine system is called “endocrinology,”
Bouin and Ancel reasoned that some secretion
which is now a well-developed branch enjoying
from the Leydig cells is involved in the develop-
the technological advancement for the investiga-
ment of the male characteristics which were later
tory and diagnostic tools in the field.
named testosterone. Pure, crystalline testosterone
Being a physiological functionary “endocrine
was extracted not until 1935.
system” bears the sets of diseases which arise of
In 1889 when Joseph von Mering and Oskar
hyper or hypo function of the specific endocrine
Minkowski described hormonal etiology of the
glands or faults in their brain part regulations or
diabetes, they observed that surgically removing
receptor activation at target site. This chapter is
the pancreas resulted in an increase of blood
dealing with the individual endocrine glands, their
sugar, followed by coma and eventually death.
central and peripheral regulations, implied hor-
In 1891, Murray successfully treated a female
monal mechanisms, and related diseases/disorders
patient with myxedema with thyroid extract.
Endocrine System
Case VI Before Insulin
Endocrine System, Fig. 2 Therapeutic effect of insulin
historically demonstrated in a diabetic girl. (Image credit:
Welcome Collection, a proprietary of Welcome Trust, UK,
In 1894, Oliver and Schaefer described the
presence of epinephrine in extracts from the adre-
nal medulla.
In 1902 William Bayliss and Ernest Starling in
a unique experiment showed that acid instilled
into the duodenum induced secretion in pancreas,
even after removing any nervous connections
between the two organs.
Nayliss and Starling discovered the hormone
secretin in 1903 and also used the first the term
“hormones” to indicate such chemical
messengers.
In 1909, MacCallum and Voetlin stated an
association between calcium metabolism and the
parathyroid glands.
In 1913, Farmi and Von den Velden treated
diabetes insipidus with posterior pituitary
extracts.
In 1921 Otto Loewi first brought the idea of
neurohormones and that year only growth
3
Case VI 4 Mos. After
available under Creative Commons Attribution Interna-
tional Licensing)
hormone (GH) was first described by Evans
and Long.
In1922 Banting and Best discovered insulin.
Insulin showed a magical effect on the health of
the diabetes patients for whom otherwise no cure
was available until then (Fig. 2). No later, Eli
Lilly, a chemist and owner of an American phar-
maceutical company, started mass production of
insulin (Fig. 3).
In 1962 Sutherland a renowned pharmacist
reported that the action of epinephrine is mediated
by secondary messengers like cyclic adenosine
monophosphate (cAMP). It was a landmark dis-
covery which unraveled the mechanism of the
action of hormones.
Evolutionary and Developmental Basis
Most animals with well-developed nervous/circu-
latory systems essentially have an endocrine
4 Endocrine System

Endocrine System, Fig. 3 An advertisement for Lilly Insulin (McCormick). (Image credit: Truman Library)

system. The endocrine system of vertebrates con- mesoderm, ectoderm); hence, the type of endo-
sists of glands and diffuse cell groups scattered in crine product is determined by the tissue layer a
epithelial tissues. Endocrine glands develop from gland originated in. Glands of ectodermal and
all three germinal tissue layers (endoderm, endodermal origin produce peptide and amine
Endocrine System 5

hormones; but mesodermal-origin glands secrete The lower most part of this brain structure projects
steroid or lipid hormones (Sadler and Langman into the pituitary (infundibular) stalk making pos-
2015; Kleine and Rossmanith 2016, terior or neurohypophyseal part of the pituitary
pp. 347–353). gland. The specific nuclei groups of hypothala-
mus involved in the secretion of hormones are
described below along with the functions.
Classification of Endocrine Glands
Function Hypothalamus is the central regulator
Endocrine glands can be classified as central and
of the entire endocrine system. Hypothalamic
peripheral. Central endocrine glands are those
neuronal cells secrete releasing/release inhibiting
which are present within the cranium and are
hormones which further stimulate/inhibit the syn-
part of the brain as hypothalamus, pituitary and
thesis of stimulating hormones from the anterior
pineal glands. The other glands existing outside
pituitary. Chiefly, arcuate nucleus of the tuberal
the cranial premises are called peripheral. Endo-
region, and also some nuclear groups in preoptic
crine glands also can be classified as primary and
and supraoptic regions, which control the secre-
secondary endocrine organs. Primary endocrine
tion of hormones from the anterior pituitary, or the
organs have the only function to secrete hormones
supraoptic and paraventicular nuclei (PVN) of
(Table 1a), but secondary endocrine organs are
supraoptic region of the hypothalamus which
primarily meant for the other biological functions
secrete oxytocin and vasopressin and
and also secrete hormones to support and sustain
corticotrophic releasing hormone (CRH) consti-
their primary functions (Table 1b). In secondary
tute endocrine part of the hypothalamus. Arcuate
endocrine organs, only specific cell groups or
and other hypothalamic nuclei controlling hor-
tissue components would be devoted for the hor-
monal secretion form the anterior pituitary send
monal secretion. Pancreas, though merits to be a
their axons to the median eminence
primary endocrine organ by definition, it is only
(hypothalamic extension which forms stalk of
partly endocrine, as it has only a specific cell
the pituitary gland) and emit their secretions
group (Islets of Langerhans) dispersed along
which get collected in the portal venous capil-
whole length of organ (mainly tail part) which is
laries present there and through the portal veins
endocrine, rest of the pancreas is exocrine –
reach to the anterior pituitary. Contrastingly, oxy-
secretes enzymes meant for digestive functions
tocin and vasopressin are synthesized by the
which exit through ducts. Similarly, hypothala-
supraoptic and paraventricular nuclei of the hypo-
mus though considered as a primary endocrine
thalamus, respectively, though are released at the
organ, only neurons in the specific nuclear groups
posterior pituitary or neurohypophysis where
are endocrine. Table 1 enlists animal endocrine
their axons are ending. Hypothalamic endocrine
glands, exiting hormones, and their major
function is regulated by the instructions from the
functions.
higher cortical centers and also through the feed-
back received from the different hierarchical
levels of the endocrine systems which are under
Endocrine Glands: Brief Anatomy and
the hypothalamic control (Kovacs and Ojeda
Hormone-Related Functions
2012, pp. 116–148, Kleine and Rossmanith
2016, pp. 269–297). Hypothalamic endocrine reg-
Primary Endocrine Organs
ulation is further discussed in this chapter in sec-
tion “Endocrine System: Physiological
Hypothalamus
Regulations.”
Structure Hypothalamus is the basal part of the
diencephalon (its upper part is called thalamus)
making the floor of the third ventricle of the brain.
 6

Endocrine System, Table 1 Animal endocrine glands, hormones, and their major functions
Glands/hormone Cell/tissue source Major functions Glands/hormone Cell/tissue source Major functions
(a) Primary endocrine organs
Hypothalamus Pituitary
Corticotropin- Paraventricular nuclei Stimulates release of ACTH and Adrenocorticotropic Anterior pituitary Stimulates synthesis and release
releasing hormone (PVN) B-endorphin from anterior hormone (ACTH) of glucocorticoids
(CRH) pituitary
Gonadotropin- Preoptic area; anterior Stimulates release of FSH and Follicle-stimulating Anterior pituitary Stimulates development of
releasing hormone hypothalamus LH from anterior pituitary hormone (FSH) ovarian follicles and secretion
(GNRH) of estrogens; stimulates
spermatogenesis
Luteinizing hormone- Nuclei; medial basal Stimulates release of LH from Growth hormone Anterior pituitary Mediates somatic cell growth
releasing hormone hypothalamus (rodents and anterior pituitary (GH)
(LHRH) primates); arcuate nuclei
(primates)
Somatostatin (growth Anterior periventricular Inhibits release of GH and TSH Luteinizing hormone Anterior pituitary Stimulates Leydig cell
hormone-inhibiting nuclei from anterior pituitary inhibits (LH) development and testosterone
hormone) release of insulin and glucagon production in males; stimulates
from pancreas corpora lutea development and
production of progesterone in
females
Melanotropin-release Arcuate nuclei Inhibits the release of MSH Melanocyte- Anterior pituitary Affects memory; affects skin
inhibitory factor (no evidence of this peptide in stimulating hormone color in amphibians
(Dopamine) humans) (MSH)
Neuropeptide Arcuate nuclei Regulation of energy balance Prolactin (PRL) Anterior pituitary Many actions relating to
Y (NPY) reproduction, water balance,
etc.
Neurotensin Arcuate nuclei Regulation of energy balance Thyroid-stimulating Anterior pituitary Stimulates thyroid hormone
hormone or secretion
thyrotropin (TSH)
Orexin A and B Lateral hypothalamic area Regulation of energy balance/ Oxytocin Posterior pituitary Stimulates milk letdown and
food intake uterine contractions during birth
Thyrotropin-releasing Paraventricular nuclei Stimulates release of TSH and Vasopressin or Posterior pituitary Increases water reabsorption in
hormone (PVN) PRL from anterior pituitary antidiuretic hormone kidney
ADH or AVP
Endocrine System
Histamine Tuberomamillary nucleus
(also from mast cells)
Kisspeptin Arcuate nucleus
Increases wakefulness, prevent Pineal gland
sleep
Acting on the receptors present Melatonin Pinealocytes Affects reproductive and
in the anterior pituitary circadian control of bodily
regulates synthesis/secretion of functions
reproductive hormones
Endocrine System

Adrenal gland Thyroid/parathyroid

Mineralocorticoids Thyroxine or Follicular cells Regulate oxidation and basic
tetraiodothyronine metabolic rates in tissue;
(T4) learning associated
Triiodothyronine neuroplasticity
(T3)
Aldosterone Zona glomerulosa of Sodium retention in kidney Calcitonin (CT) C-cells of thyroid Lowers serum Ca2+ levels
adrenal cortex
11- Zona glomerulosa of Sodium retention in kidney Parathyroid Parathyroid gland Stimulates bone resorption;
Deoxycorticosterone adrenal cortex hormone (PTH) increases serum Ca2+ levels
(DOC)
Glucocorticoids
Cortisol Zona fasciculata and Increases carbohydrate Pancreas (Islet cells of Langerhans)
(hydrocortisone)/ z. reticularis of adrenal metabolism; antistress hormone
corticosterone cortex Increased carbohydrate Glucagon a-cells Glycogenolysis in liver
metabolism; antistress hormone Insulin b-cells Glucose uptake from blood;
glycogen storage in liver
Dehydroepiandro- Zona reticularis of adrenal Weak androgen; primary Somatostatin d-cells Inhibits insulin and glucagon
sterone DHEA cortex secretory product of fetal secretion
adrenal cortex Pancreatic Peripheral cells of Effects on gut in
polypeptide (PP) pancreatic islets pharmacological doses
Epinephrine or Adrenal medulla Glycogenolysis in liver;
adrenaline (EP) increases blood pressure
Norepinephrine or Adrenal medulla Increases blood pressure
noradrenaline (NE)
Ovary
Estrogen Follicles (also in brain Uterine and other female tissue Progesterone Corpora lutea, Uterine development;
regions like hippocampus, development Enhances placenta mammary gland development;
hypothalamus, prefrontal cognition, neuroprotective maintenance of pregnancy
cortex, amygdala)
Inhibin . . .. . .. . ..
7

(continued)
 8

Endocrine System, Table 1 (continued)

Glands/hormone Cell/tissue source Major functions Glands/hormone Cell/tissue source Major functions
Testes
Androstenedione Leydig cells Male sex characters Testosterone Leydig cells Spermatogenesis; male
secondary sex characters
Dihydrotestosterone Seminiferous tubules and Male secondary sex characters
(DHT) prostate
(b) Organs with secondary endocrine function
Organ Hormone Major functions Organ Hormone Major functions
Lung Leukotrienes (LT) Long-acting Multiple organs Prostaglandins E1 and Contraction/relaxation of
bronchoconstrictors E2 PGE1 and PGE2 smooth muscle cells in vessels,
aggregation/disaggregation of
platelets, sensitization to pain
(and other actions)
Heart Atrial naturetic factor Regulation of urinary sodium Multiple organs Klotho Enhances cognition, protects
(Atrial myocytes) (ANF) excretion against aging
Thymus Thymosin, thymulin and Proliferation/differentiation of Skin Cholecalciferol Modified to form Vit. D
(Thymocytes) thymopoietin lymphocytes
Kidney Renin Stimulates release of Liver Insulin like growth Stimulates bodily growth
aldosterone factor (IGF-1)
Calcitriol Helps absorption of Ca2+ Angiotensinogen Raises blood pressure
Erythropoietin Induces absorption of red blood Thrombopoietin Causes increase in platelets
cells in bone marrow
Endocrine System
Skeleton FGF23 Inhibits production of calcitriol Hepcidin Blocks release of iron into body
and increases phosphate fluids
excretion
Osteocalcin Increase insulin secretion Gut
Adipose tissue Leptin Promotes satiety signals in the Bombesin Neurons and Hypothermic hormone;
Endocrine System

brain endocrine cells of gut increases gastrin secretion

Adiponectin Reduces insulin resistance Cholecystokinin Duodenum and CNS Stimulates gallbladder
(CCK) contraction and bile flow;
affects memory, eating behavior
Placenta Gastric inhibitory Duodenum Inhibits gastric acid secretion
polypeptide (GIP) G-cells of midpyloric Increases secretion of gastric
Gastrin glands in stomach acid and pepsin
antrum
Chorionic Placenta LH-like functions; maintains Gastrin-releasing GI tract Stimulates gastrin secretion
gonadotropin (CG) progesterone production during peptide (GRP)
pregnancy
Chorionic Placenta Acts like PRL and GH Vasoactive intestinal Small intestine (also in Inhibits gastric acid secretion
somatomammotropin peptide (VIP) central and enteric and increases intestinal
or placental lactogen nervous system, and secretion of water and
(CS) nerve terminals) electrolytes; a neurotransmitter/
neuromodulator in CNS/ENS
Serotonin GI tract and blood Maintain mood, sleep, appetite,
platelets (also a and digestion. Regulate bowel
neurotransmitter in function and movements
brain)
9
10
Endocrine System, Neurosecretory cells
Fig. 4 Hypophyseal portal
circulation
Capillary plexus
Hypophyseal artery
Endocrine cells
Adenohypophysis
Pituitary vein
Pituitary Gland
Structure Pituitary gland is the master controller
of all peripheral primary endocrine glands. This
gland is located in the hypophyseal fossa (also
called pituitary fossa) which is placed in the center
of middle cranial fossa of base of the skull. Embry-
ological derivation of this gland is unique. Poste-
rior half of the gland is the extension of the
hypothalamus hence neural and is called neurohy-
pophysis. The neurohypophysis contains the axons
terminals of the neurons supraoptic and PVN
nuclei of the supraoptic region of the hypothala-
mus. Anterior part of the gland is derived from the
evagination of the oral ectoderm infront of the
buccopharyngeal membrane and is called adeno-
hypophysis. Most of the pituitary hormones are
secreted from the adenohypophysis part except
oxytocin and vasopressin or antidiuretic hormone
(ADH) which are secreted from the neurohypoph-
ysis part (Kovacs and Ojeda 2012, pp. 116–171).
Function The hypothalamic releasing or inhibi-
tory hormones regulate the synthesis of trophic
hormones from the anterior pituitary through
hypophyseal portal system (Fig. 4). Posterior pitu-
itary hormones oxytocin and vasopressin regulate
hemodynamic status of the body. Oxytocin is also
involved in induction of the delivery and ejection
of breast milk in female (Kovacs and Ojeda 2012,
pp. 148–171). Both of the hormones have effect
on animal social behavior, memory, and learning,
especially oxytocin, which is also called social
molecule (Kumar et al. 2018).
Endocrine System
Hypothalamus
Portal veins
Neurohypophysis
Pineal Gland
Structure Pineal is a minute pine cone like gland
located at the rear end of the diencephalon. The
cellular elements of the gland are pinealocytes
(approx. 95%) and neuroglia cells, and it is
densely filled with afferent nerve terminals. The
gland is highly vascular and rich in sympathetic
innervations.
Function Pineal gland secretes (by pinealocytes)
a serotonin-derived photoactive hormone melato-
nin which helps regulate circadian rhythm of the
body (to regulate the sleep and wakefulness) in
concert with the biological clock situated in the
supra-chiasmatic nuclei (SCN) of the hypothala-
mus. It is also a known powerful antioxidant.
Melatonin secretion is regulated by light exposure
and its intensity and shows a rhythmic secretion,
being low during the daylight hours and high
during dark periods.
Melatonin is also believed to be involved in
sexual development and reproductive functions
(blocks secretion of LH and FSH), thermoregula-
tion, cellular metabolism, and also in immune
function. Though there is little evidence in
human that the pineal gland plays a significant
role in the neuroendocrine regulation of reproduc-
tion during either puberty or adulthood, in season-
ally breeding animals, such as sheep and
hamsters, melatonin secretion is said to be
influenced by the day length and thus gating
reproduction as a function of the season (Kleine
and Rossmanith 2016, pp. 243–244).
Endocrine System
T4 T4
5’Deiodinase
T3
T3
I– I–
NIS
+
2Na 2Na+
Blood
vessel
Endocrine System, Fig. 5 Synthesis of Thyroid hormones. I: ionized iodine; I0: oxidized iodine; Tg: thyroglobulin;
TPO: thyroid peroxidase
Thyroid Gland
Structure Thyroid gland is situated in the neck
extending from C5 to T1 vertebrae and is related
with laryngeal cartilages and upper tracheal rings.
It is a butterfly-like structure having two lobes and
a connecting isthmus that lies in front of 2–4th
tracheal rings. The lobes lie on either side of the
larynx and trachea and whole gland is covered by
pretracheal fascia. In some individuals, an extra
smaller lobe of thyroid called pyramidal lobe may
be present, which may extend from the isthmus up
to the hyoid bone.
Function Thyroid gland secretes hormones Tri-
iodothyronine (T3) and Tetra-iodothyronine or
Thyroxine (T4) which are involved in the regula-
tion of the basic metabolic rate of the body
(influencing physiological functioning of almost
each cell and the organ). Thyroid hormones are
secreted from the lining epithelial cells of the
follicles which further go iodination in the colloid
filled in the lumen of the follicles (Fig. 5). Iodine
11
MIT Tg I0
Hydrolysis I0
Tg
Tg
DIT
I– I0 Tg
I0
I– I0
TPO
Single
thyroid
cell
Thyroid
follicle
is exclusive to and an essential component of the
thyroid hormones. The term “iodine” here refers
to the elemental form of the iodine (I) which will
get assimilated in the hormones in the iodide form
(I
). Ingested iodine is absorbed through the small
intestine and transported in the plasma to the
thyroid, where it is concentrated, oxidized, and
then incorporated into thyroglobulin (Tg) to
form intermediate mono and diad (MIT and DIT)
and later final and active triad (T3) and tetra (T4)
forms of thyroid hormones in the thyroid follicles,
and is stored there for a variable period (Fig. 5).
Further, Tg base of the thyroid hormones undergo
proteolysis releasing T3 and T4 into the circulation
to be carried by specific binding proteins to target
tissues. The synthesis of T4 is about 4 times more
than T3. Its vast influence is mediated through
differential expression of hormone receptor iso-
forms in tissues and conversion of thyroxine (T4)
to triiodothyronine (T3), by the enzyme
50 -deiodinase (Fig. 5). The thyroid hormone
secretion is controlled by thyrotropin-releasing
hormone (TRH) from hypothalamus and thyroid
12
stimulating hormone (TSH) from anterior pitui-
tary along with nutritional signals like availability
of the iodine and carrier molecules, and also by
the environmental factors like radiation, chemical
exposure, drugs, and temperature. Calcitonin is a
small polypeptide hormone secreted by the para-
follicular or “C” cells of the thyroid. Calcitonin
decreases blood calcium and increases blood
phosphate level by suppressing the osteoclast
activity in bones and increasing the amount of
calcium excreted in urine (Kleine and Rossmanith
2016, pp. 269–297).
Parathyroid
Structure The small glands (about 50 mg), two
each side, are normally found on the posterior
aspect of the lobes of thyroid gland.
Function Parathyroid gland secretes parathyroid
hormone (PTH) that controls calcium and phos-
phate homeostasis in the body. Effect of PTH on
blood calcium and phosphate levels is opposite of
calcitonin for which it is known as an antagoniz-
ing hormone.
Adrenal Gland
Structure Adrenal gland is a small gland located
on the top of each kidney enclosed in renal fascia
(alternative name for this is suprarenal gland). It
has cortical and medullary parts which secrete
steroid and amine hormones respectively. The
cortex is further differentiated into pars
glomerulosa, fasiculata, and reticularis. Central
medullary part contains chromaffin and ganglion
cells of neural crest origin.
Functions Its cortical and medullary parts
secrete distinct hormones which are involved in
maintaining important physiological functions.
Cortical Hormones The pars glomerulosa,
fasiculata, and reticularis secreting sex steroids
or gonadotrophins, mineralcorticoids, and gluco-
corticoids or cortisol in order. All cortical hor-
mones are steroid compounds derived from
cholesterol.
Endocrine System
Gonadotrophins The adrenal cortex secretes
many male sex hormones, including DHEA,
DHEA sulfate (DHEAS), androstenedione, and
11-hydroxyandrostenedione, and also small quan-
tities of the female sex hormones progesterone
and estrogen. Androgens secreted from the adre-
nal go extra-adrenal conversion to testosterone.
These androgens have a role in early development
of the male sex organs in childhood. They also
mediate secondary sexual characteristics during
puberty in the both sexes. ACTH from anterior
pituitary has a physiological stimulatory effect on
androgen release by the adrenal.
Mineralocorticoids Aldosterone accounts for
most of the mineralocorticoid activity, with some
contribution from glucocorticoids. The concentra-
tion of aldosterone in blood exhibits diurnal var-
iation, and the secretory rate is generally
150–250 mg/day. Aldosterone promotes sodium
reabsorption and potassium excretion by the tubu-
lar epithelial cells of the collecting and distal renal
tubules thus way maintaining normal osmolality
and water balance in blood. Reabsorption of
sodium is followed by passive absorption of
water, leading to an increase in the extracellular
fluid volume with minimal change in the plasma
sodium concentration.
Glucocorticoids Most of the glucocorticoid
activity comes from cortisol, with corticosterone
having a minor contribution. The normal blood
cortisol concentration averages 12 mg/dL, with an
average secretory rate of 15–20 mg/day. Cortisol
secretion from adrenal gland is the output hor-
mone in HPA axis, and also it is the chief stress
hormone in body. Other functions of cortisol are
like counteracting insulin secretion, stimulating
gastric-acid secretion, reducing bone formation,
and functioning as a diuretic. Cortisol also con-
tributes to the maintenance of various homeostatic
actions, like blood pressure, immune system,
metabolism of protein, carbohydrate, and fat,
and anti-inflammatory action. Its secretion is con-
trolled by the hypothalamo-pituitary-adrenal
(HPA) axis, which follows a circadian rhythm
and also gets influenced by exposure to the light
and hours of the sleep (vice versa it regulates
Endocrine System
sleep) (Longo 2015, Chapter 399; Kleine and
Rossmanith 2016, pp. 339–346). Its regulation
through HPA axis and neural and molecular
basis of rhythmic secretion are further discussed
in this chapter in section “Endocrine System:
Physiological Regulations.”
Medullary Hormones The chromaffin and gan-
glion cells in the medulla secrete epinephrine/
adrenalin and norepinephrine/noradrenaline and
in minute amount dopamine. These hormones
are secreted into the bloodstream as a result of
direct stimulation by acetylcholine release from
the sympathetic nerves. Preganglionic sympa-
thetic nerve fibers reach to the chromaffin cells
of the adrenal medulla without synapsing any-
where else. These hormones are responsible for
the maintenance of cardiac output, physiological
vascular resistance, and stress response (Kleine
and Rossmanith 2016, pp. 269–297).
Ovary
Structure Ovary is the female gonad located in
the pelvis one on each side at the terminal end
(fimbria) of the uterine tube. A single follicle is the
endocrine unit of the ovary. Each follicle contains
a germ cell/oocyte at the core surrounded by an
inner and an outer layer composed of granulosa
cells and theca cells, respectively.
Function It secretes the hormones which are
essential for the maintaining functions and health
of their reproductive organs. Ovary chiefly
secretes estrogen and progesterone which are,
respectively, responsible for the initiation and
maintenance of the pregnancy, and also secretes
androstenedione and testosterone in slighter
amount which can get converted to estrogen
with aromatization. Estrogen also shows a termi-
nal surge which induces secretion of the oxytocin
which in turn would initiate uterine contraction to
facilitate delivery of the child. Ovary also secretes
minor nonsteroidal hormones as activin, inhibin,
and relaxin. Nonsteroidal ovarian hormones have
a contribution in regulating production of steroid
hormones though chief regulation is by LH and
FSH by anterior pituitary (activin enhances, and
13
inhibin and relaxin suppress). Relaxin also relaxes
the hip ligaments before delivery of the child.
Estrogens also have effect on the physiological
processes other than reproduction such as bone
metabolism/remodeling, nervous system matura-
tion, and endothelial responsiveness. Estrogen
also brings pubertal changes in female like breast
development and enlargement and maturation of
the uterus, ovaries, and vagina. Estrogen also
works in concert with growth hormone and
insulin-like growth factor I (IGF-I) to produce a
growth spurt and stimulates the maturation of
chondrocytes and osteoblasts, which ultimately
leads to epiphyseal fusion. Until midpuberty,
estrogen begins to exert a positive feedback on
gonadotropin-releasing hormone (GnRH) secre-
tion, leading to the progressive increase of LH
and FSH production, culminating in the LH
surge, ovulation, and the initiation of the men-
strual cycle. In the adult female, estrogen plays a
critical role in maintaining the menstrual cycle
(Kovacs and Ojeda 2012, pp. 194–238, Kleine
and Rossmanith 2016, pp. 269–297).
Testes
Structure Testis is the male gonad which in con-
trast to the female gonad, along with the external
genitalia presents in the perineal region, present
bilaterally enclosed in scrotal sac.
Function It chiefly secretes testosterone which is
necessary for the gametogenesis and also devel-
opment and maintenance of the male reproductive
system and male sexual behavior. Higher center
regulation of testosterone synthesis is much sim-
pler than the female sex hormones due to absence
of a defined cyclic period in male. The male sex
hormones secreted from adrenal gland make addi-
tional source of this hormone through conversion.
Pancreas (Islet Cells)
Structure Islet cells of the pancreas which are
dispersed among the exocrine acini as clusters
constitute endocrine part of this organ. Islet cell
clusters are more abundant towards rear part of the
organ with highest density in the tail.
14
Function Islet cells secrete three types of the
hormones: alpha cells secrete glucagon, beta
cells insulin, and delta cells somatostatin, respec-
tively, which are crucial for the normal metabolic
functions of the body. Insulin and glucagon con-
trol the two opposite aspects of glucose metabo-
lism, glycogenesis and glycogenolysis,
respectively, in consequent control concentration
of glucose in blood. Insulin is also involved in the
metabolism of many other energy storing bio-
molecules which finally reduce blood glucose
level.
Organs/Tissue Components with Secondary
Endocrine Function
Certain animal organs contain a tissue component
or specific cell groups with endocrine functions
(Table 1b). Below is being provided a brief
descriptions of such endocrine structures and
their functions.
Placenta
Structure Placenta is an endocrine organ of
pregnancy. All female mammals other than mono-
tremes and marsupials (most) bear placenta during
pregnancy. Placenta is implanted in the uterine
wall, where it receives nutrients and oxygen
from the mother’s blood and passes out excretory
products. It is a disc like structure. Uniquely, it has
maternal and fetal components both providing a
physical link between the two. Maternal and fetal
components are derived from uterine decidua
(functional layer of the endometrium which is
shed during parturition) and chorionic frondosum
(an outer trophoblast shell and inner chorionic
plate made of extraembryonic mesoderm), respec-
tively (Sadler and Langman 2015, p. 112). It is the
fetal component, especially the syncytial layer of
the trophoblast cells, which is endocrine, and
secretes hormones to sustain pregnancy.
Functions Placenta secretes progestins (mainly
progesterone) along with the corpus luteum.
It also secretes estrogen (especially weaker
estriol) which inhibit the LH along with the pro-
gesterone to help sustain pregnancy and induce
growth of the breast. During initial 2 months of
Endocrine System
the pregnancy, syncytial cells of the trophoblast
secrete human chorionic gonadotrophin (HCG),
which helps to maintain corpus luteum until pla-
centa takes the action of synthesizing progester-
one. HCG also inhibits LH like gonadotrophins to
stop further ovulations and to help sustain preg-
nancy. This hormone is excreted in the maternal
urine in initial months of the pregnancy and is
used as a gestational indicator. Another hormone
secreted by the placenta is somatomammotropin
(placental lactogen), which is a growth hormone
like substance, providing fetus a priority on mater-
nal glucose and inducing maternal glucose syn-
thesis hence making the mother functionally
diabetic during pregnancy. It also helps growth
of the breast in mother (Sadler and Langman
2015, pp. 116–117).
Thymus
Structure The thymus is a double lobed struc-
ture located in the upper anterior part of chest
directly behind sternum. It has an outer zone
called cortex and an inner zone called medulla.
Histologically, the organ is composed of two
types of cell called lymphocytes and reticular
cells. The cortex bears the immature T cells
which migrate to the medulla in order to mature
(Standring 2016, pp. 1362–1365).
Function Thymus produces hormones like thy-
mosin (alpha 1), thymulin, and thymopoietin,
which have been stated to circulate through
blood and to act on both prothymocytes and
mature T-cells in the periphery which helps to
maintain commitment and functions of these
cells. The hormones produced by the thymus pro-
mote the maturation of the T cells prior to their
release into the blood. Once these thymic lympho-
cytes (or T cells) have fully matured in the thy-
mus, they migrate to the lymph nodes in the body
and guard against invader microorganisms or liv-
ing or nonliving foreign particles causing dis-
eases, a biological function called immune
surveillance (Kleine and Rossmanith 2016,
pp. 269–297; Standring 2016, pp. 1362–1365).
Endocrine System
Adipose Tissue
Adipose tissue secretes several hormones. These
hormones are mainly involved in lipid metabo-
lism and storage. Adiponectin – a hormone syn-
thesized by adipose cells – appears to reduce
cellular insulin resistance and to protect blood
vessels from inflammation and atherosclerosis.
Leptin, synthesized by the adipose cells, acts as
an indicator of satiety. It is released in response to
food and acts on the neuronal regions dealing with
the energy intake and expenditure (Kleine and
Rossmanith 2016, pp. 269–297).
Skin
The skin cells synthesize inactive form of vitamin
D3, cholecalciferol from cholesterol when
exposed to ultraviolet radiation. Cholecalciferol
is converted to an intermediate in liver, which
further is converted to calcitriol – the active form
of vitamin D3, in kidney. Vitamin D is important in
a variety of physiological processes, including
intestinal calcium absorption and immune system
function (Kleine and Rossmanith 2016,
pp. 269–297).
Skeleton
Bone cells secrete Fibroblast growth factor
23 (FGF23). Its action is to inhibit the formation
of calcitriol from vitamin D3 and to increase phos-
phorus excretion from kidney. Osteocalcin, from
the osteoblasts, induces insulin secretion from
pancreas and also promotes its responsiveness
on the peripheral tissues (Longo 2015, chapter
423).
Heart
Specialized cells in the atrium wall secrete the
peptide hormone atrial natriuretic peptide (ANP)
in response to distension caused by increased
blood volume or pressure. ANP has a role in
maintaining hemodynamic status of the body. It
reduces sodium reabsorption and, in turn,
decreases accompanied water reabsorption from
the urinary filtrate in the kidney, bringing down
the total blood volume. It also has an inhibitory
effect on the renin secretion from the specialized
cells of the kidney tubules, hence initiation of the
renin-angiotensin-aldosterone system (RAAS)
15
which has an opposite effect on hemodynamic
balance in the body (Kleine and Rossmanith
2016, pp. 269–297).
Gastrointestinal Tract
The mucosa of the GI tract, mainly the stomach
and small intestine, contains specialized cell
which secrete hormones meant to help in the
digestion. Like, G-cells in the stomach secrete a
peptide hormone, gastrin, in response to disten-
sion caused by entering food that stimulates the
release of hydrochloric acid from other cells. Sim-
ilarly, secretin, a peptide hormone, is secreted by
the small intestine in response to the acidic chyme
released from stomach. Secretin stimulates the
release of bicarbonate from the pancreas, antago-
nizes acidic chyme, and also inhibits the further
secretion of hydrochloric acid by stomach
mucosa. Cholecystokinin (CCK) is another pep-
tide hormone released from small intestine which
induces the secretion of digestive enzymes from
pancreas and also the release of bile from the
gallbladder. Intestinal hormones are also involved
in glucose metabolism, like gastrin inhibitory
peptide-1 (GIP-1) and glucagon like peptide-
1(GLP-1) secreted from the small intestine induce
secretion of insulin (Kleine and Rossmanith 2016,
pp. 269–297; Kumar et al. 2018).
Liver
The endocrine function of liver is highly involved
in metabolic regulation of the digestive nutrients.
It synthesizes various hormones such as insulin-
like growth factor (somatomedin),
angiotensinogen, thrombopoietin, and hepcidin.
IGF-1 has insulin-like effects as its name sug-
gests, and it can bind to the insulin receptor. Its
actions are mediated through a same named tyro-
sine kinase receptor which presents on the surface
of almost all cells and is the stimulus for growth in
the body. Angiotensinogen by the action of
enzyme renin secreted from the kidney gets
converted to angiotensin which is a substrate of
Renin-Angiotensin-Aldosteron System (RAAS)
maintaining hemodynamic balance in the body.
Angiotensin also causes vasoconstriction (Kleine
and Rossmanith 2016, pp. 269–297). Hepcidin is
small peptide hormone majorly synthesized in the
16 Endocrine System

liver. It is chief regulator of the extra cellular

excretion of the iron in the body (Gressner and
Gressner 2018).
HO

Cholesterol O
Kidneys
Certain cells of kidney secrete hormones which O
are crucial for hemodynamic and electrolyte bal- O
ance in the body. A decline in blood flow which is Pregnenolone Progesterone
detected at the glomerular filtration system HO

induces release of the enzyme renin, which in

O
turn switches on the RAAS stimulating the Cortisol Aldosterone
DHEA
reabsorption of sodium and water leading to
OH
increase in blood flow and blood pressure. The HO
OH
kidneys regulate blood calcium levels through the
production of calcitriol from vitamin D3, which is HO
O Testostero
released in response to the secretion of PTH. Low
ne (and Estradiol (and other
oxygen level in circulation induces synthesis of other estrogens)
erythropoietin (EPO) from kidney which in turn androgens)
would stimulate the production of red blood cells
Endocrine System, Fig. 6 Cholesterol derivations of the
(erythrocytes) in the bone marrow, thereby
lipid hormones
increasing oxygen delivery to tissues
(Mukoyama and Nakao 2005).
Endocrine System, Table 2 Neurohormones
Corticotropin-releasing Thyrotropin-releasing
Hormones Hormone (CRH) Hormone
Gonadotropin-releasing Histamine
Hormone (GNRH) Vasopressin or antidiuretic
Types and Structure Luteinizing hormone- Hormone)
Hormones are mostly proteins, but some are also releasing ADH or AVP
peptides, amines, or steroids. The protein, peptide, Hormone (LHRH) Oxytocin
or amine hormones are water soluble, but steroid Somatostatin (growth Norepinephrine
Hormone-inhibiting Dopamine
hormones are lipid soluble. Lipid-soluble hor- Hormone) Serotonin
mones act slow, but their effects last longer than Melanotropin-release Melatonin
water soluble hormones (Kleine and Rossmanith Inhibitory factor B-endorphin
2016, pp. 11–17; Kumar et al. 2018). Lipid hor- (dopamine) Agouti-related protein
Neuropeptide Y (NPY) (AGRP)
mones have a common molecule of origin as Neurotensin Estrogen
cholesterol (Fig. 6). Most of the hormones are Orexin A and B
secreted by peripheral organs or specific tissue Reproduced with permission from Hormones and Behav-
components. Some hormones are synthesized ior, Kumar A. et al., 2018, Encyclopedia of Animal Cog-
inside the brain which are called “neurohor- nition and Behavior, Springer Nature
mones” (Table 2). Neurohormones also include
some of the sex hormones (estrogen, progester-
one, and testosterone) which are also synthesized These hormones attach to the receptors present
by cortical neurons (Ish et al. 2007). on the surface of target cells creating the
hormone-receptor complex, in turn engaging a
Mechanisms of Action G-protein dependent secondary messenger path-
Protein, peptide, and amine hormones (except way (like cAMP, cGMP, Diacylglycerol, Ca++,
thyroid hormones) are water soluble, hence can- etc.,) to induce protein kinases/phosphorylases
not cross through the cell membrane directly. related to specific biological events. Steroid
Endocrine System
a Hormone
Protein, peptide,
amine hormones
receptor
complex
Cell surface receptor
Secondary
messenger
Protein
enzymes++
Endocrine System, Fig. 7 Mechanisms of action (a)
Protein, peptide, and amine hormones (b) Steroid and
thyroid hormones. (Reproduced with permission from
hormones are lipid soluble, hence can cross
through the cell membranes. They directly reach
nucleus tagged with transporters or binding pro-
tein present in the cell cytoplasm, where they set
free from the carrier molecule and attach to the
nuclear receptors (binding sites) at DNA promoter
regions for the genes assigned for forming specific
proteins (Fig. 7) (Kleine and Rossmanith 2016,
pp. 263–267; Kumar et al. 2018).
Thyroid hormones, though chemically amine,
are exception to the group. Their three dimen-
sional structure resembles that of the steroid hor-
mones, hence can enter the cell and reach to the
specific nuclear receptors with the help of specific
transporters present at the cell membrane
(facilitated diffusion) and in the cell cytoplasm.
Hormones are biologically active in very minute
amount which get usually measured in micrograms
(mg, 10
6 g), nanograms (ng, 10
9 g), or picograms
(pg, 10
12 g). Hormone-Receptor interactions for
all categories of hormones are highly specific,
reversible, and satiable and follow a threshold limit
for the maximal biological response (i.e., follow
normal distribution curve). Also, there is differential
purposing of the category of hormones depending
17
b
Steroid and Thyroid
hormones
Molecular
transporters
Coding of mRNAs
Protein synthesis
Hormones and Behavior, Kumar A. et al., 2018, Encyclo-
pedia of Animal Cognition and Behavior, Springer Nature)
on the metabolic processes involved. Metabolic
processes which need urgent response, such as
blood glucose or calcium homeostasis, are usually
controlled by peptide hormones (also epinephrine),
but processes for which response is slow, such as
pubertal development or basic metabolic rate, are
controlled by steroid hormones and thyroid hor-
mones. Electrolyte homeostasis requires intermedi-
ate response speed and is regulated by peptide and
steroid hormones both (Kleine and Rossmanith
2016, pp. 263–267).
Hormone Secretion, Transport, and
Degradation
The blood level of a hormone is determined by its
rate of secretion and its circulating half-life. After
protein processing, peptide hormones are stored in
secretory granules, from where are later released
into the circulation. The stimulus for hormone
secretion may be a releasing factor or neural signal
that induces rapid changes in intracellular calcium
concentrations, leading to secretory granule
fusion with the plasma membrane and release of
the hormones. In contrast, steroid hormones dif-
fuse into the circulation as they are synthesized
18 Endocrine System

Endocrine System, Table 3 BBB free regions in brain

Circumventricular organs
1. Organum vasculosum of lamina terminalis
2. Subfornical organ
3. Subcommissural organ
4. Median eminence (hypothalamus)
5. Intermediate lobe of pituitary gland
6. Posterior pituitary
7. Pineal gland
8. Area postrema (4th ventricle)
Reproduced with permission from Hormones and Behav-
ior, Kumar A. et al., 2018, Encyclopedia of Animal Cog-
nition and Behavior, Springer Nature

hence their secretory rates are closely aligned with

rates of the synthesis.
Hormone transport and degradation determine
the speed with which a hormonal signal may
decay. Some hormonal signals are short decaying
(e.g., somatostatin), whereas others are longer-
lived (e.g., TSH). An understanding of circulating
hormone half-life is necessary for the proper phys-
iologic hormone replacement (Longo 2015, chap-
ter 399). Endocrine System, Fig. 8 Feedback regulations at cen-
tral endocrine axes

Crossing Blood Brain Barrier (BBB)

Transport of a hormone through blood brain bar-
rier (BBB) depends on whether it is water or lipid
soluble. Steroid hormones are lipid soluble, hence
can easily pass to and fro through the BBB (the
peripherally synthesized hormones enter brain
and those synthesized inside brain reach to periph-
ery), but protein, peptide, amine, and other hor-
mones which are water soluble can do it with help
of the transporters/binding proteins only. Trans-
port of the lipid insoluble hormones is a saturable/
rate limited process due to exhaustion of the trans-
porters/binding proteins (Banks 2012; Kumar
et al. 2018).
Certain of the hormone synthesizing brain
regions, called circumventricular organs, are
devoid of a blood brain barrier (BBB) which
facilitates the release of the stored hormones in
the blood (Table 3) (Kumar et al. 2018).
These BBB-free regions are also the site for
receiving peripherally released hormones. These
brain regions contain receptors for the peripheral
hormones – presenting a unique opportunity for
neuron-hormone interactions.
Endocrine System: Physiological
Regulations
Central Endocrine Axes and Hormonal
Homeostasis
The endocrine system is governed by the central
axes which essentially connects three components
of the system: a brain component – a nuclei of the
hypothalamus, anterior part of the pituitary gland,
and any of the endocrine glands as adrenal,
gonads, or thyroid. Each axis is regulated by the
feedback cycles (Fig. 8) (Kleine and Rossmanith
2016, pp. 299–338; Kumar et al. 2018). Table 4
mentions the central axes, their essential compo-
nents, and secreted hormones.
Central endocrine axes run from hypothalamus
to adrenal, gonads, or thyroid via anterior part of
Endocrine System
Endocrine System, Table 4 Central endocrine axes in the animals (including human)
Hypothalamic component/
Name hormone
Hypothalamic- Paraventricular nucleus (PVN)/
pituitary- adrenal corticotrophin releasing
(HPA) axis hormone (CRH)
Hypothalamic- Paraventricular nucleus
pituitary-thyroid PVN/thyrotrophin releasing
(HPT) axis hormone (TRH)
Hypothalamic- Arcuate nucleus/gonadotrophin
pituitary-gonadal releasing hormone (GnRH)
(HPG) axis
pituitary (adenohypophysis). Hypothalamus in
association with anterior pituitary and adrenal
gland constitutes HPA axis – which bears an
influence on most of the neurophysiological func-
tions and is crucial for the neuroendocrine adap-
tation to the stress. A parallel axis connecting
hypothalamus and anterior pituitary to gonads
(testis in male and ovary in female) constitutes
HPG axis which regulates reproductive functions.
In HPG axis, releasing/inhibitory hormones are
secreted from specific hypothalamic nuclei
which induce synthesis/release of stimulating/
luteinizing hormones from anterior pituitary
which in turn induce synthesis/release of sex hor-
mones from the gonads. The peripheral endocrine
glands and their central regulatory centers work in
coordination in an attempt to maintain a state of
functional equilibrium or physiological homeo-
stasis in the body (Kleine and Rossmanith 2016,
pp. 299–338).
Feedback regulation also occurs for endocrine
systems that do not involve the central axes, for
example, calcium feedback on PTH, glucose inhi-
bition of insulin secretion, and leptin feedback on
the hypothalamus.
Uniquely, prolactin a hormone secreted from
the anterior pituitary essential for the control of
the lactation in female and many other functions
has only two components in its regulatory axis-
(hypothalamo-prolactin axis) which does not con-
tain an inter-gland feedback loop. The dopamine
secreted from the tubero-infundibular nuclei of
the hypothalamus is inhibitory to the secretion of
19
Target
endocrine
organ/
Pituitary component/hormone hormone
Adrenocorticotrophs, anterior pituitary/ Cortisol/
adrenocorticotrophin hormone (ACTH) cortisone
Thyrotrophs, anterior pituitary/thyroxine Thyroxine
stimulating hormone (TSH) 3 and 4
(T3 and T4)
Gonadotrophs, anterior pituitary/follicle Estrogen/
stimulating hormone (FSH)/leutinizing progesterone
hormone (LH)
prolactin from the anterior pituitary and also sets
auto-inhibition of its own secretion (Macleod
et al. 1981).
Paracrine and Autocrine Regulation
Paracrine regulation refers to factors released by
one cell that act on an adjacent cell in the same
tissue, such as somatostatin secretion by pancre-
atic islet cells inhibits insulin secretion from
nearby cells. Autocrine regulation states the
action of a factor on the same cell from which it
is produced, such as IGF-I acts on the cells that
produce it to regulate its secretion.
Circadian Control of Endocrine Functions
SCN and PVN nuclei of hypothalamus regulate
circadian release of hormones. Pineal gland is also
known to maintain circadian release of melatonin
which depends on exposure of the organism to the
light. The circadian release of any hormone from
the hypothalamic and pineal nuclei is affected by
the duration and intensity of the light exposure.
The SCN and other hypothalamic nuclei are
connected to the retina – screening portal of the
light, through bidirectional retinohypothalamic
connections. Pineal gland nuclei are also
connected to this circuitry through to and fro
channels. Control of circadian rhythm through
hypothalamic nuclei is a complex biological pro-
cess which is genetically determined and con-
served among species (Tsang et al. 2014;
Andreani et al. 2015). The molecular repertoire
maintaining circadian rhythms (Table 5) are not
20
Endocrine System, Table 5 Molecular repertoire
of SCN
Brain and muscle ARNT like protein-1 (Bmal1)
Clock (or Npas2 in neuronal tissue)
Cryptochrome (cry) 1,2
Period (per)1,2,3
E-box
Retinoid-related orphan receptor (Ror) a, b, l
Rev-Erb a, b
Chrono
Casein kinase 1 (ck1) d, e
Reproduced with permission from Hormones and Behav-
ior, Kumar A. et al., 2018, Encyclopedia of Animal Cog-
nition and Behavior, Springer Nature
present only in the endocrine organs but in many
organs and tissues, which together create a com-
plex molecular network system with a central
command from SCN (Hughey and Butte 2016).
Cortisol, the HPA axis output hormone, also
follows circadian rhythm, with its peak secretion
in the morning at 8 AM with lesser serum values
along the day, with minimum at 4 PM.
A dysregulation of circadian synthesis/release of
the hormones is implicated in metabolic syn-
dromes and neuroendocrine disorders including
stress-induced psychiatric disorders and sleep dis-
orders (Kleine and Rossmanith 2016,
pp. 299–338; Kumar et al. 2018).
Endocrine-Nervous-Immune Cross-Regulation
Endocrine system is an autonomous but not a
completely independent physiological unit. It
has noted cross regulation with the nervous and
immune system – which meant that hormones
interact with the neuropeptides/neurotransmitters
and immune cell derived cytokines. Evidence
suggests that interaction between these systems
is bidirectional and a dysregulation of it implicates
in etiogenesis of the diseases like metabolic and
psychiatric disorders (Kelley 1988).
Effects of Aging on Endocrine System
Most hormone levels decrease with aging. Salient
hormones which decrease with aging are GH,
Endocrine System
IGF-1 and melatonin, and sex hormones like
DHEA, estrogen, and progesterone. Decline of
the melatonin may play an important role in the
loss of circadian rhythms with aging. Sex
hormone-binding globulin is reported to increase
with age in both sexes. Levels of some hormones
may also increase, like LH and FSH, and pancre-
atic polypeptide and gastrin (but not other gut
hormones). For some hormones, their levels
remain near normal with aging, these are thyroid
(except T3, which is reduced possibly due to
decrease conversion from T4). Parathyroid hor-
mone shows an increase that may be due to
decreased renal excretion. Adrenal cortical hor-
mones like glucocorticoid and mineralocorticoid
show higher serum concentrations with aging
though the target organ for mineralocorticoid
activity (kidney), however, becomes less respon-
sive. For adrenal medullary hormones like epi-
nephrine and norepinephrine, their baseline
serum concentrations increase with aging though
stimulable increases in both (as percentages of the
basal concentrations) show a decrease. The circa-
dian patterns for the hormones showing diurnal
variation like cortisol, norepinephrine, and
growth hormone are altered in aged.
In female, fall of the female sex hormones
(estrogen and progesterone) is marked by meno-
pause near the age of 45 years with rise of LH and
FSH (LH initially may show a fall at commence-
ment of menopause). In males, there is a gradual
fall of testosterone and increase of LH and FSH
with aging called andropause. Insulin secretion is
impaired and insulin resistance increases with
age. Levels of androgens in female and estrogen
in male may not show much change with aging
(Chahal and Drake 2007).
Endocrine Disorders
Each endocrine organ has specific disorders
which may alter functions of the related physio-
logical systems. Certain of the endocrine diseases/
disorders present as the syndrome involving many
organs. Endocrine disorders can result from dys-
function originating in the peripheral endocrine
gland itself (primary disorders) or under stimulation
Endocrine System
or overstimulation by the central regulators of an
endocrine axis as anterior pituitary, or hypothalamic
nuclei (secondary disorders). The disorders can
result in hormone overproduction (hyperfunction)
or underproduction (hypofunction). Rarely, endo-
crine disorders (usually hypofunction) occur
because of reduced responses from the target site
receptors (Longo 2015, chapter 399; Kleine and
Rossmanith 2016, pp. 357–376).
Endocrine disorders may also happen from
exogenous or self-administration of a hormone,
or due to a blockade in the regulatory axis for an
endocrine gland (such as HPA axis), or in
response of a diseased state (Longo 2015, chapter
399).
Hypofunction of a peripheral endocrine gland
can be caused by congenital (like a genetic disor-
der resulting from deletion of a gene), or acquired
disorders (like autoimmune and vascular disor-
ders, tumors, infections, toxins, or hormone
receptor hypofunction). Some hormones require
conversion to an active form after secretion from
the synthesizing gland, which may happen in
some other glands, a dysfunction of the organ
where activation has to take place, may result in
hormonal hypofunction. For example, inactive
form of Vitamin D is synthesized in the liver
which requires further modification in kidney
and skin, respectively, to become active, a disease
of kidney or skin may result in hypofunction of
vitamin D. Primary hyperfunction of endocrine
glands generally results from hyperplasia or neo-
plasia of the gland. Other reasons for this can be
ectopic production of a hormone from a different
tissue as may happen in cancers and autoimmune
diseases (as in hyperthyroidism of Graves’ dis-
ease). Table 6 provides a detailed list of endocrine
diseases/disorders with anatomical and functional
abnormality for each.
Commonly Used Investigations
The concentration of hormones in blood or serum
in the living animal can be investigated with the
immunoassays (radio-, enzyme-, and
fluorescence-immunoassay) and more recently
high-performance liquid chromatography
(HPLC) and mass-spectrometry combined with
gas chromatography (MS–GC). The general
21
investigations used for in vitro determination of
hormones or their receptors are immunocyto-
chemistry (ICC), autoradiography, in situ hybrid-
ization, and blotting. Medical imaging techniques
(like PET scan and f-MRI) which reveal organ
activation during certain actions or behaviors,
paired with endocrine manipulations or monitor-
ing, can provide important information (Fusani
2017). For human cases, taking patient history
and clinical examination is the first thing to be
done for an endocrine disorder, which would pave
the way which tests should be conducted to reach
a diagnosis. Hematology and urinalysis provide
important information in diagnosing endocrine
disorders. Other investigations are available to
test the function of specific endocrine glands.
Medical imaging like CT and MRI scans, sonog-
raphy, and scintillation counting are useful for
detecting change in the size of endocrine glands
and the presence of tumors or cysts. Karyotyping
for the chromosomal errors, or genotyping, or
sequencing for mutation analysis, and
genomewide association study for single nucleo-
tide polymorphisms (SNPs) or copy number var-
iations (CNVs) are also done for the disorders
where a genetic basis is speculated (Fusani 2017;
Kumar et al. 2018).
Common Therapeutic Approaches
Control of the hypersecretion (surgical removal,
radio or chemosuppression, or using a pharmaco-
logical agent as the antagonist) and replacement or
correction of the deficiency (by pharmacological or
dietary means, or treating the causes) are the main
stream approaches for treating the endocrine dis-
orders (Longo 2015, chapter 399–409). Recently,
gene-based therapeutic approaches have shown
promises for this where a genetic basis is known.
Known gene-based approaches are either correc-
tion of the faulty genes through genomic editing
or gene supplementation or using antisense oligo-
nucleotides against the targeted genes. Gene ther-
apy is considered more suitable for correcting the
monogenic endocrine disorders like GH defi-
ciency or familial hypercholesterolemia, though
newer advances in gene-based therapy have also
raised hope for the multifactorial diseases like
diabetes mellitus or endocrine cancers, and
Endocrine System, Table 6 Major endocrine disorders, their causes, clinical features, diagnostic investigations, and management
22

Glands Disorders Pathology/causes Signs and symptoms Diagnostic investigations Management

Hypothalamus Trauma Symptoms caused by Hormone analysis, Hormone replacement
deficiency of pituitary, neuroimaging
Tumors adrenal or gonadal hormones. Hormone analysis, Surgical removal of the
Symptoms are also specific to neuroimaging tumor. radiotherapy, hormone
the etiology replacement
Kallmann syndrome Genetic mutation Hormone analysis,Genetic Gene correction, hormone
screening replacement
Anorexia Nervosa and Hormone analysis Hormone replacement
Bulimia Nervosa
Prader-Willi Symptoms caused by Hormone analysis Hormone replacement
syndrome deficiency of pituitary,
Inflammatory and adrenal, or gonadal Hormone analysis, Hormone replacement
vascular diseases, hormones. Symptoms are
malnutrition, also specific to the etiology
infection, radiation
Central precocious Early release of GnRH from Early onset of puberty GnRH stimulation testing GnRH analogue therapy
puberty hypothalamus may be due to
brain injury or a pituitary
tumor
Pituitary Cushing’s disease Excessive production of Weight gain, high blood Blood hormone analysis, Surgical removal of tumor/
ACTH due to some tumor pressure, thinning of the skin, neuroimaging medication
easy bruising, etc.
Acromegaly Excessive production of GH Abnormally increased height Blood hormone analysis, Surgical removal of tumor/
due to some tumor neuroimaging medication
Pituitary growth Due to low secretion of GH Decreased height Blood hormone analysis, Surgical removal of tumor/
failure neuroimaging medication
Hypogonadotr opic Low LH and FSH Delayed puberty Blood hormone analysis, Surgical removal of tumor/
hypogonadism Leading to low secretion of neuroimaging medication
testicular/ovarian hormones
Pituitary masses Excessive production of some Large masses may compress Blood hormone analysis, Surgical removal of tumor/
hormones, like in surrounding tissue, erode into neuroimaging medication
prolactinoma bone, or produce excess
hormone
Hypopituitarism Surgery, radiation treatments, Nonspecific, including Blood hormone analysis, Surgical removal of tumor/
large pituitary tumors, weakness, fatigue, and neuroimaging hormone replacement
Endocrine System
 bleeding or loss of blood
supply
Central diabetes Damage to the pituitary gland
insipidus (or hypothalamus) disrupting
the normal production,
storage and release of ADH
Due to surgery, a tumor, an
illness (such as meningitis),
inflammation or a head injury
or an inherited genetic
disorder (in children), of an
unknown cause
Thyroid and Hyperthyroidism Excessive production of
parathyroid thyroid hormones due to
autoimmune conditions
(Graves disease) or
inflammation
Hypothyroidism Low production of thyroid
hormones due to autoimmune
conditions or inflammation,
surgery, radiation, drug
induced
Thyroiditis Excess/low production of
thyroid hormones due to
autoimmune conditions
((Hashimoto’s thyroiditis) or
infections, hypersensitivity
Tumors Benign and cancerous
Hyperparathyroidism Excess parathyroid hormone
(PTH) in the blood, caused by
tumorous growth in
parathyroid gland
dizziness, headache,
occasional loss of
consciousness
Intense thirst even after Urine and blood tests, water Medication (desmopressin a
drinking fluids (polydipsia), deprivation test. synthetic ADH analogue),
Endocrine System
and excretion of large Investigations for underlying management of waterloss,
amounts of urine (polyuria), causes electrolyte imbalance and
electrolyte imbalance water loss
Restlessness, agitation, Blood hormone analysis, Medication, radioactive
anxiety, tremors, weight loss, tests for specific antibodies iodine therapy
sweating, rapid heart rate,
intolerance to heat, and,
frequent bowel movements
Tiredness, feeling cold, Thyroid hormone analysis, Thyroid hormone
weight gain, dry skin, increased blood TSH replacement
constipation, and swelling
(edema) of the face or ankles
Sign and symptoms of hyper/ Testing for the thyroid Depending on the hormonal
hypo thyroidism peroxidase (TPO) antibody in analysis
the blood/thyroid hormone
analysis
Pressure in the neck, FNAC (biopsy), radioisotope Surgical removal, radioactive
hoarseness of the voice, or scan iodine therapy
difficulty in swallowing or
breathing, metastatic
symptoms
Increased blood calcium Blood hormone analysis Calcium monitoring, surgery
levels can cause symptoms of
tiredness, poor concentration,
low mood, bone pain, and
stomach or abdominal
symptoms
23
(continued)
Endocrine System, Table 6 (continued)
Glands Disorders Pathology/causes
Adrenal Hypercortisolism Excess production of adrenal
hormone cortisol secondary to
Cushing’s syndrome or an
adrenal tumor
Hyperaldosteronism Excess production of adrenal
hormone aldosterone due to a
tumor or nodular disease
Adrenal insufficiency Reduced hormone secretion
from the adrenal gland,
resulting in deficiency of all
adrenal hormones, including
cortisol and aldosterone.
Reasons may be autoimmune
destruction of the adrenal
gland (Addison’s disease),
bleeding into the adrenal
glands, or infections, such as
tuberculosis
Adrenal masses Mostly benign and rarely
cancerous tumors. May
produce excess adrenal
hormones
Ovary Ovarian insufficiency Ovaries either do not develop,
(sometimes called or are damaged hence no
premature longer function normally
menopause)
Polycystic ovary Small cysts in the ovaries,
syndrome (PCOS) increased amount of
androgens produced by the
ovaries
24
Signs and symptoms Diagnostic investigations Management
High blood pressure, weight Blood and/or urine testing Medication, surgical removal
gain, thinning of the skin, of the tumor
easy bruising, poor wound
healing
Low potassium in the blood Blood test, adrenal vein Medication, surgical removal
and high blood pressure sampling of the tumor
resistant to treatment
Weakness, weight loss, Blood hormone analysis, Hormone replacement
dizziness, and sometimes screening for specific
abdominal pain, nausea, and antibodies
vomiting
Symptoms of Ultrasound, CT and MRI, Clinical monitoring, surgery
hyperaldosteronism and histopathology
corticosolism
Symptoms of low estrogen Blood hormone analysis Hormone replacement
can develop in many, but not
all: hot flashes, night sweats,
poor sleep, and vaginal
dryness. Infertility and the
loss of the beneficial effects
of estrogen and progesterone
Irregular menstrual periods, Blood tests for sex hormone, Ovulation induction by
loss of fertility, increased hair ultrasound medication, surgery
growth on the face, chest, or
abdomen, acne, and a
tendency toward weight gain
and insulin resistance
(diabetes)
Endocrine System
Testis Low testosterone Due to testicular trauma, Reduced energy, mood, Blood hormonetest/clinical Testosterone replacement
levels in men radiation or chemotherapy for strength, and libido radiological evaluation
certain types of cancer,
infection or loss of blood
supply to the testes
Primary testicular Genetic causes Reduced energy, mood, Blood hormone analysis/ Testosterone replacement
Endocrine System

hypogonadism strength and libido, infertility genetic screening

Androgen Genetic causes Female phenotypic features Blood hormone analysis/ Management for functional,
insensitivity with male genetic makeup, genetic screening sexual, and psychological
syndromes infertile issues
Pancreas (islet Diabetes mellitus Dysfunction of insulin Insulin resistance is related to Blood test for glucose level, For type 1 diabetes, synthetic
cells) production/secretion (type 1), the metabolic changes of late HbAc, insulin insulin must be administered
or the target cells’ pregnancy, and the increased by injection or infusion.
responsiveness to insulin insulin requirements may For type 2, life style changes
(type 2) lead to IGT or diabetes and insulin
Gestational diabetes mellitus
(GDM)
Neuroendocrine Sign and symptoms depend Serum hormone and analysis Hormone replacement,
tumors like on the hormone involved Genetic screening, CT, MRI surgery, medication
insulinoma,
gastrinoma,
glucagonoma,
carcinoid tumor, etc.
Multiple Multiple endocrine Primary Serum calcium and PTH, Genetic screening for
endocrine neoplasia I and II hyperparathyroidism, adrenal hormone estimation mutations, surgery/
organs (MEN I and MEN II) hypercalcemia, (elevated levels of serum medication
hypophosphatemia, increased calcium and intact
secretion of epinephrine/ parathyroid hormone)
norepinephrine CT, MRI
Polyglandular Mutations, inherited disorder Sign and symptoms depend Serum hormone analysis Hormone replacement
autoimmune (Pga) on the hormone involved Genetic screening
syndromes
25
26
obesity (Barzon et al. 2000). In case of autoim-
mune endocrine disorders, targeting the genes
coding for the culprit immune molecules has
been a successful approach. Suicide gene therapy
(using a tumor and/or tissue specific gene which
converts a pro-drug into a toxic substance which
would kill the tumor cell) has been successfully
used to treat endocrine tumors (Barzon
et al. 2000).
Cross-References
▶ Circadian Rhythms
▶ Estrogen
▶ Hormones and Behavior
▶ Hypothalamus
▶ Stress
▶ Testosterone
▶ Thyroid and Adrenal Glands
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