Chapter 13 – The Endocrine System

13.1 Overview of the Endocrine System

Endocrine glands: ductless glands that secrete hormones, chemical messengers that are carried
by the blood to distant target cells

Body endocrine glands include: pituitary, thyroid, parathyroid, adrenal and pineal
Hormone secreting organs and tissues: hypothalamus, skin, thymus, heart, liver, stomach,
pancreas, kidneys, small intestine, ovaries, testes, adipose tissue and placenta

Endocrine system: all endocrine glands and hormone secreting cells

-Hormones influence target cells by binding to specific protein receptors

-Generally a target cell has 2000 to 100,000 receptors for a particular hormone

Down-regulation: when a hormone is in excess, the number of target cells decreases, making
the target cell less sensitive to the hormone

Up-regulation: when a hormone is deficient, the number of target cells increases, making the
target cell more sensitive to the hormone

Hormones are classified as either lipid soluble or water soluble

Lipid soluble: steroid and thyroid hormones
-Steroid hormones: derived from cholesterol and contain four interconnected hydrocarbon
rings and include aldosterone, cortisol, dehydroepiandrosterone (an adrenal androgen),
testosterone, estrogen and progesterone, calcitriol (active form of vitamin D) is structurally
similar to a steroid and thus included
-Thyroid hormones: T3 and T4, made by attaching iodine to amino acid tyrosine and contain
two hydrocarbon rings

Water soluble hormones include amine hormones and peptide/protein hormones

-Amine hormones are synthesized by modifying certain amino acids: the catecholamines:
epinephrine, norepinephrine and dopamine are derived from the AA tyrosine, melatonin is
derived from tryptophan
-Peptide/protein hormones: amino acid polymers, most hormones belong in this category,
smaller peptide hormones consist of chains of 3 to 49 AAs, larger protein hormones include 50
to 200 AAs
-examples of peptide hormones are antidiuretic hormone (ADH) and oxytocin
-examples of protein hormones include insulin and growth hormone
-glycoprotein hormones are protein hormones that have an attached carbohydrate group, such
as thyroid-stimulating hormone
-most water-soluble hormones circulate through the watery plasma in a “free” form
-most lipid-soluble hormones are bound to transport proteins because they are not soluble in
blood, about 0.1%-10% of the molecules of a lipid-soluble hormone are not bound to a
transport protein, this free faction diffuses out of capillaries, binds to receptors and triggers
responses and as free hormones leave the blood to bind to their receptors, transport proteins
release new ones to replenish the free faction

-a hormone’s mechanism of action depends on the signalling

-the receptors for a hormone may be present either in the plasma membrane of the target cell
or inside the target cell
-water-soluble hormones cannot pass through the hydrophobic membrane so they bind to
plasma membrane receptors, lipid-soluble hormones can pass through so they can bind to
intracellular receptors located in the cytosol or in the nucleus

Mechanisms of action of lipid-soluble hormones

-when lipid-soluble hormones such as steroid hormone or thyroid hormone binds to an
-intracellular receptor, the signalling pathway that is activated typically alters gene expression
-the receptor-hormone complex binds to DNA, either stimulating or inhibiting the transcription
of a specific gene, as DNA is transcribed, mRNA is formed and translated, resulting in the
formation of a new protein (the effector protein) that alters the cell’s activity and causes the
cellular response
-lipid soluble hormones can also have nongenomic effects, meaning they can activate signaling
pathways that change the activity of proteins in the target cell without altering gene expression

Mechanisms of water-soluble hormones

-when a water-soluble hormone binds to a plasm membrane receptor, the signaling pathway
that is activated depends on the type of receptor involved
-the receptors for water-soluble hormones include G protein-coupled receptors, receptor
tyrosine kinases, receptor guanylyl cyclases and janus kinase-coupled receptors

-a hormone can have several different target cells

-a given cell can serve as the target for many different hormones, when this is the case the
target cell has several types of receptors, each responding to only its specific hormone

-the responsiveness of a target cell to a hormone depends on three factors: hormone

concentration, number of the target cell’s hormone receptors and influences exerted by other
hormones
-a target cell responds more vigorously when the level of a hormone rises or when it has more
receptors

-some hormones require a simultaneous or recent exposure to a second hormone to cause a

greater response in their target cells, the second hormone is said to have a permissive effect
-when the effects of two hormones acting together is greater than the sum of their individual
effects, they are said to have a synergistic effect
-when one hormone opposes the actions of another hormone, the two hormones are said to
have antagonistic effects

-the release of most hormones occurs in short bursts, with little or no secretion between
bursts; when stimulated, the endocrine gland releases its hormones in more frequent bursts,
increasing the blood concentration of the hormone

-hormone secretion can be regulated by: signals from the nervous system, chemical changes in
the blood, distension of an organ or other hormones
-tropic hormones (tropins): hormones that act on other endocrine glands or tissues to regulate
the secretion of another hormone

-most hormonal regulatory systems work via negative feedback

13.2 Pituitary Gland

-the pituitary gland (hypophysis) is a pea sized structure that extends from the brain, it consists
of two lobes, a larger anterior pituitary and a smaller posterior pituitary
-anterior pituitary: glandular epithelial tissue; posterior pituitary: nervous tissue

-the master of the pituitary gland is the hypothalamus, the small region of the brain below the
thalamus
-the infundibulum connects the pituitary gland to the hypothalamus
-hypothalamus synthesizes at least nine different hormones, while the pituitary gland secretes
six

-anterior pituitary (adenohypophysis) secretes hormones that regulate a variety of different

bodily functions from growth to reproduction
-there are five types of anterior pituitary cells
1. somatotrophs: secrete growth hormone (GH) also known as somatotropin which
stimulates body growth and metabolism
2. thyrotrophs: secrete thyroid stimulating hormone (TSH) or thyrotropin which controls
the secretions and other activities of the thyroid gland
3. corticotrophs: secrete adrenocorticotropic hormone (ACTH) or corticotropin stimulates
the adrenal cortex to release glucocorticoids like cortisol
4. lactotrophs: secrete prolactin (PRL) which initiates milk production in the mammary
glands
5. gonadotrophs: secrete two different gonadotropins, follicle-stimulating hormone (FSH)
and luteinizing hormone (LH), they both act on the gonads and in men they stimulate
the testes to produce sperm and secrete testosterone, while in women they stimulate
the ovaries to produce eggs and secrete estrogen and progesterone
-release of anterior pituitary hormones is controlled by the hypothalamus, the hypothalamus
secretes five releasing hormones which stimulate secretion of anterior pituitary hormone:
1. growth hormone-release hormone (GHRH) or somatocrinin stimulates GH secretion
2. thyrotropin-releasing hormone (TRH) stimulates TSH secretion
3. corticotropin-releasing hormone (CRH) stimulates ACTH secretion
4. prolactin-releasing hormone stimulates PRL secretion
5. gonadotropin-releasing hormone (GnRH) stimulates FSH and LH secretion

The hypothalamus also produces two inhibiting hormones that suppress the secretion of
anterior pituitary hormones:
1. growth hormone-inhibiting hormone (GHIH) also known as somatostatin, suppresses GH
secretion
2. prolactin-inhibiting hormone (PIH) which is dopamine, suppresses PRL secretion

hypothalamic hormones reach the anterior pituitary through a portal system called the
hypothalamic-hypophyseal portal system
-a portal system is a type of vascular arrangement in which blood flows from one capillary
network through a portal vein and then into a second capillary network without first returning
to the heart

Regulation of the anterior pituitary by the hypothalamus occurs as follows:

 specialized neurons of the hypothalamus called neurosecretory cells synthesize the
hypothalamic releasing or inhibiting hormones and package them in vesicles and are
moved via axonal transport to the axon terminals for storage
 when hypothalamus neurosecretory cells are excited APs trigger the exocytosis of the
vesicles causing the hormones to be released and then they diffuse into the
hypothalamic-hypophyseal portal system
 after hypothalamic hormones reach anterior pituitary, they diffuse out of the blood
stream and interact with anterior pituitary cells, which then secrete hormones into the
capillaries of the anterior pituitary, which drain into venous blood
 anterior pituitary hormones then travel through the blood stream to their target organs

-anterior pituitary hormones are also regulated by negative feedback, the secretory activity of
three types of anterior pituitary cells (thyrotrophs, corticotrophs and gonadotrophs) decreases
when blood levels of their target gland hormones rise

-somatotrophs are the most numerous cells in the anterior pituitary and GH is the most
plentiful anterior pituitary hormone
-GH promotes growth of body tissues and regulates certain aspects of metabolism
-GH exerts its growth-promoting effects indirectly through small protein hormones called
insulin-like growth factors (IGFs) or somatomedins
-IGF synthesized in the liver enter the bloodstream as hormones that circulate to target cells
throughout the body to cause growth
-IGF synthesized in the skeletal muscle, cartilage and bone act locally as autocrines or
paracrines to cause growth in those tissues
-GH uses IGFs as mediators

Metabolic effects of GH
-increase growth of bones and soft tissues
-enhance lipolysis
-decrease glucose uptake

TSH
-stimulates the synthesis and secretion of two thyroid hormones, triiodothyronine (T3) and
thyroxine (T4), both produced by thyroid gland
-TRH from hypothalamus controls TSH secretion
-TRH secretion depends on both levels of T3 and T4, high levels will result in inhibition of TRH
and TSH

ACTH
-stimulates the production and secretion of cortisol and other glucocorticoids by the cortex of
the adrenal glands
-CRH from hypothalamus controls ACTH
-CRH is released in response to stress related stimuli such as low blood sugar, physical trauma
and interleukin-1, a substance produced by macrophages
-CRH and ACTH are regulated by glucocorticoids using negative feedback

PRL
-together with other hormones initiates and maintains milk production by the mammary glands
-weak effect by itself, works permissively with estrogen, progesterone, glucocorticoids, GH,
thyroxine and insulin
-ejection of milk depends on oxytocin which is released by posterior pituitary
-lactation: milk production and ejection
-too much PRL in men, impotence, in females galactorrhea, amenorrhea

FSH
-initiates egg creation and secretion of estrogen
-stimulates sperm production in males

LH
-triggers ovulation in women, stimulates the formation of the corpus luteum the ovary and the
secretion of estrogen and progesterone
-stimulates testes to secrete testosterone
The posterior pituitary releases oxytocin and antidiuretic hormone (ADH) also known as
vasopressin
-posterior pituitary aka neurohypophysis stores and releases hormones
-neurosecretory cells in the paraventricular and supra optic nuclei of the hypothalamus
synthesize oxytocin and ADH

oxytocin – during delivery it enhances the contraction of smooth muscle in the uterus and after
delivery it stimulates milk ejection from the mammary glands in response to mechanical
stimulus (baby suckling)

ADH – decreases urine production and causes kidneys to return more water to the blood
-normal urine output is 1-2 liters per day, without ADH it would increase to as much as 36 liters
per day
-ADH also constricts arterioles, increasing blood pressure
-ADH secretion is stimulated by a rise in blood osmolarity and a decrease in blood volume
-osmoreceptors monitor blood osmolarity (neurons in hypothalamus)
-baroreceptors detect changes in blood volume
-ADH targets are the kidneys and smooth muscle in blood vessel walls
-alcohol inhibits ADH (why you have to pee more)

13.3 Thyroid Gland

-parafollicular cells or C cells lie between the follicles of the thyroid gland and they produce
calcitonin which helps regulate calcium homeostasis
-thyroid cells are produced by follicular cells by adding iodine to tyrosine, an AA
-process includes:
 iodide trapping
 synthesis of thyroglobulin (TGB) in follicular cells
 oxidation of iodide – I- needs to become I (removal of electrons) and this is done via
thyroid peroxidase
 iodination of tyrosine – some of AAs in TGB are tyrosine and I reacts with tyrosine parts
of TGB, one iodination causes monotiodotyrosin (MIT) and two iodinations creates
diiodotyrosine (DIT), TGB attached with iodine is called a colloid
 MIT and DIT couple up to form either T3 or T4, T3 and T4 are stored in a colloid form,
thyroid follicles typically have enough colloid for a 100 day supply of thyroid hormones
 colloid droplets reenter cells via pinocytosis and merge with lysosomes, where TBG is
broken down, allowing T3 and T4 to be cleaved off
 T4 is secreted in a greater quantity than T3, but T3 is more potent, most T4 in body cells
is converted to T3 by deiodinases which remove one of the iodine
 more than 99% of T3 and T4 in transported in the blood via a transport protein, mainly
thyroxine-binding globulin (TBG)

-thyroid hormones increase BMR and maintenance of body temperature because as ATP is
used, BMR increases, more heat is given off and body temp rises – calorigenic effect
-they have permissive effects on catecholamines (epinephrine and norepinephrine) they
upregulate beta-adrenergic receptors, promoting sympathetic responses
-they regulate growth of nervous tissue and bones

secretion of thyroid hormones is regulated by hypothalamus and anterior pituitary

-low T3 or T4 levels or low BMR stimulates hypothalamus to release TRH
-TRH causes TSH secretion in anterior pituitary
-TSH stimulates follicular cells in thyroid to produce T3 and T4
-high levels of T3 and T4 inhibit TRH release from hypothalamus (negative feedback)

-calcitonin is created in C cells of thyroid gland and it lowers blood calcium levels by inhibiting
osteoclast activity, which reduces calcium and phosphate ions being released from bone matrix
into the blood
-calcitonin promotes bone formation and decreases blood calcium and phosphate levels

13.4 Parathyroid Gland

-secretory cells in parathyroid gland called chief sells secrete parathyroid hormone (PTH)
-PTH major regulator of blood calcium, magnesium and phosphate ions
-PTH increases osteoclast activity, promoting calcium to be released from bone matrix
-PTH acts on kidneys by slowing calcium and magnesium loss in urine, and increasing phosphate
loss in urine (decreasing blood phosphate levels and increasing blood Ca and Mg levels)
-promotes formation of calcitriol in kidneys, active form of vitamin D
-calcitriol stimulates an increased absorption of calcium from foods in the GI tract

-blood calcium levels directly controls the secretion of both calcitonin and PTH via negative
feedback loops
-high calcium levels promotes calcitonin to be released from thyroid glands (parafollicular cells)
-low calcium levels promotes PTH to be released from parathyroid gland

13.5 Adrenal Gland

-there are two adrenal glands, one lying on top of each kidney, and each gland consists of two
regions, an outer adrenal cortex and inner adrenal medulla
-adrenal cortex produces a variety of steroid hormones
-adrenal medulla produces three catecholamine hormones, epinephrine, norepinephrine and
dopamine

Adrenal cortex consists of three zones that secrete hormones:

outer – zona glomerulosa - mineralocorticoids
middle – zona fasciculata – glucocorticoids
inner – zona reticularis – weak androgens
Mineralocorticoids
-major one is aldosterone, which regulates sodium and potassium homeostasis and promotes
excretion of H+ ions in the urine, and removal of acids
-secretion of aldosterone is controlled by the renin-angiotensin-aldosterone pathway (RAA)

-decreased blood volume and pressure stimulates kidneys to produce renin, renin coverts
angiotensinogen to angiotensin I, which circulates through the body and is converted by
angiotensin-converting enzyme (ACE) to angiotensin II, angiotensin II stimulates adrenal cortex
to secrete aldosterone
-in kidneys, aldosterone increases sodium reabsorption, which also causes more water to be
reabsorbed and aldosterone causes kidneys to secrete potassium and H+ into urine
-increased water absorption means increased blood volume and pressure
-ang II causes vasoconstriction in arterioles to increase blood pressure
-an increase of potassium in the blood can also stimulate aldosterone

Glucocorticoids
-regulate metabolism and resistance to stress
-include cortisol (hydrocortisone), corticosterone and cortisone
-cortisol is the most abundant and about 95% of glucocorticoid activity
-glucocorticoids controlled by negative feedback, low levels trigger CRH to by released from
hypothalamus, causing ACTH to be released from anterior pituitary which act on adrenal cortex
to secrete glucocorticoids

-glucocorticoids increase protein breakdown, increase glucose formation, stimulate lipolysis,

have anti-inflammatory effects, are resistant to stress and depress immune responses

Weak androgens
-main androgen is dehydroepiandrosterone (DHEA)
-testosterone is converted to another androgen, dihydrotestosterone (DHT)
-androgen effects weak in men but more seen in women
-promote sex drive (libido) and are converted into estrogens by other body tissues
-after menopause all female estrogens comes from the conversion of adrenal androgens
-stimulate growth of armpit and pubic hair in men and women

Adrenal Medulla
-an extension of the sympathetic nervous system
-a modified sympathetic ganglion of the ANS
-hormone producing cells called chromaffin cells secrete epinephrine (80%) and norepinephrine
(20%)
13.6 Pineal Gland
-secretes melatonin, an amine hormone derived from serotonin
-influences circadian rhythms
-low levels of melatonin secreted during the day, higher levels, secreted at night
-melanopsin is the photopigment that detects light activity
-melatonin induces sleep, protects against free radicals and inhibits reproductive function

13.7 Pancreas
-exocrine portion (about 99% of pancreas) secretes fluids containing digestive enzymes into
ducts
-endocrine portion (about 1% of pancreas) consists of clusters of cells called pancreatic islets
(islets of Langerhans) that secrete hormones

alpha cells (17%) secrete glucagon which increases blood sugar levels
beta cells (70%) secrete insulin which decreases blood sugar levels
delta cells (7%) secrete somatostatin which inhibit both insulin and glucagon release, slows
absorption of nutrients in GI tract and inhibits secretion of GH
F cells secrete pancreatic polypeptide which inhibits somatostatin secretion, gallbladder
contraction and secretion of digestive enzymes by the pancreas

-GLUT4 is an insulin dependent glucose transport and not found in liver or transport epithelia of
the kidneys and intestine
-14 glucose transporters

-insulin causes uptake of glucose, promotes formation of glycogen via glycogen synthase,
prevents glycogenolysis in the liver and suppresses gluconeogenesis and promotes uptake of
fatty-acids and formation of triglycerides and uptake of AAs to form proteins

-glucagon is an insulin antagonist and its main target cell is a hepatocyte (liver cell)
-it promotes gluconeogenesis and glycogenolysis, and promotes lipolysis and inhibits protein
formation

-hyperglycemia (high blood sugar) stimulates insulin release

-hypoglycemia (low blood sugar) stimulates glucagon release

insulin also stimulated by increased blood AA levels, and increased activity of PS nerves
glucagon also stimulated by increased S nerves activity

13.8 Ovaries and Testes

-ovaries secrete two estrogens, estradiol and estrone, and progesterone as well as inhibin
which inhibits FSH and relaxin which inhibits uterine contractions, making it easier for a
fertilized egg to implant in the uterine wall
-testes secrete testosterone and inhibin as well
13.9 Other Endocrine Organs and Tissues

-skin produces cholecalciferol, vitamin D3, which plays a role in the synthesis of calcitriol
-7-dehydrocholesterol which is found in skin is converted to cholecalciferol when skin is
exposed to UV rays in sunlight, cholecalciferol is converted to 25-hydroxycholecalciferol where
its circulated to the kidneys where it is then converted to calcitriol
-calcitriol increases calcium and phosphate absorption in GI

-the thymus produces thymosin and thymopoietin which promote the maturation of T cells

-the heart produces atrial natriuretic peptide (ANP) which inhibits the absorption of sodium
ions and water by the kidneys, making them more lost in urine, this decreases blood volume
and blood pressure

-the liver produces 25-hydroxycholecalciferol and thrombopoietin which stimulates platelet

production

-the stomach produces gastrin which promotes gastric juice secretion and increases motility
(contractions) of the stomach
-ghrelin stimulates appetite
-secretin stimulates secretion of pancreatic juice that is rich in bicarbonate ions
-cholecystokinin (CCK) stimulates secretion of pancreatic juice that is rich in digestive enzymes
and promotes gallbladder contractions to release stored bile to bring full feeling after eating
-GIP and GLP stimulate insulin release from pancreas

-kidneys secrete calcitriol and erythropoietin which increases rate of erythrocyte production

-fat tissues secrete leptin, which reduces appetite and thus food intake when there is lots of
adipose tissue present