Chapter 18 - Introduction to the Endocrine System

The Endocrine System regulates long-term processes; e.g., Growth, Development & Reproduction
Uses chemical messengers to relay information and instructions between cells
Homeostasis and Intercellular Communication
1. Direct Communication: Exchange of ions and molecules between adjacent cells across gap
junctions: occurs between two cells of same type, highly specialized and relatively rare
2. Paracrine Communication: Uses chemical signals to transfer information from cell to cell
within single tissue; most common form of intercellular communication
3. Endocrine Communication: Endocrine cells release chemicals (hormones) into bloodstream:
alters metabolic activities of many tissues and organs simultaneously
4. Synaptic communication: Across synaptic clefts - neurotransmitters
Target Cells - specific cells that possess receptors needed to bind and “read” hormonal messages
Hormones
1. Stimulate synthesis of enzymes or structural proteins
2. Increase or decrease rate of synthesis
3. Turn existing enzyme or membrane channel “on” or “off”
Hormones can be divided into three groups
1. Amino acid derivatives – T4, epinephrine, melatonin
2. Peptide hormones – FSH, ADH, PRL
3. Lipid derivatives – Testosterone, estrogen, cortisol
Circulate freely or bound to transport proteins
Secretion and Distribution of Hormones: free Hormones: remain functional for less than 1 hour
o Diffuse out of bloodstream - bind to receptors on target cells
o Are broken down and absorbed - by cells of liver or kidney
o Are broken down by enzymes - in plasma or interstitial fluids
Thyroid and Steroid Hormones: remain in circulation much longer; enter bloodstream & more than
99% become attached to special transport proteins; bloodstream contains substantial reserve of
bound hormones
Mechanisms of Hormone Action
Hormone Receptor is a protein molecule to which a particular molecule binds strongly
o Responds to several different hormones
o Different tissues have different combinations of receptors
o Presence or absence of specific receptor determines hormonal sensitivity
Hormones and Plasma Membrane Receptors
Catecholamines and peptide hormones
o Are not lipid soluble & unable to penetrate plasma membrane
o Bind to receptor proteins at outer surface of plasma membrane (extracellular receptors)
o Cannot have direct effect on activities inside target cell
o Use intracellular intermediary to exert effects
1st messenger: leads to 2nd messenger; may act as enzyme activator, inhibitor or cofactor; results
in change in rates of metabolic reactions
Important Second Messengers
1. Cyclic-AMP (cAMP) - Derivative of ATP
2. Cyclic-GMP (cGMP) - Derivative of GTP
3. Calcium ions
Process of Amplification: binding of a small number of hormone molecules to membrane receptors
- leads to thousands of 2nd messengers in cell; magnifies effect of hormone on target cell
Down-regulation: presence of a hormone triggers  in number of hormone receptors; when
levels of particular hormone are high, cells become less sensitive
Up-regulation: absence of a hormone triggers  in number of hormone receptors; when levels
of particular hormone are low, cells become more sensitive
Hormones and Plasma Membrane Receptors
G Proteins: Enzyme complex coupled to membrane receptor; involved in link between 1 st
messenger & 2nd messenger; binds GTP; activated when hormone binds to receptor at membrane
surface & changes levels of 2nd messenger cyclic-AMP (cAMP) within cell:  cAMP level 
metabolic activity within cell
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G Proteins & Calcium Ions: activated G proteins trigger: opening of Ca ++ channels in membrane &
release of Ca++ from intracellular stores; G protein activates enzyme phospholipase C (PLC)
 Enzyme triggers receptor cascade: production of diacylglycerol (DAG) & inositol
triphosphate (IP3) from membrane phospholipids
Hormones & Intracellular Receptors: alter rate of DNA transcription in nucleus; change patterns
of protein synthesis; directly affects metabolic activity & structure of target cell (steroids &
T3/T4)
Endocrine Reflexes: functional counterparts of neural reflexes; mainly through negative
feedback mechanisms; stimulus triggers production of hormone whose effects reduce intensity
of the stimulus
Endocrine reflexes can be triggered by
1. Humoral stimuli: changes in composition of extracellular fluid
2. Hormonal stimuli: arrival or removal of specific hormone
3. Neural stimuli: arrival of neurotransmitters at neuroglandular junctions
Simple Endocrine Reflex involves only 1 hormone; controls hormone secretion by heart, pancreas,
parathyroid gland & digestive tract
Complex Endocrine Reflex involves 1 or more steps; 2 hormones; includes hypothalamus
Neuroendocrine Reflexes pathways include both neural and endocrine components
Complex Commands : issued by changing
 Amount of hormone secreted
 Pattern of hormone release: hypothalamic and pituitary hormones released in sudden bursts;
frequency changes response of target cells
The Pituitary Gland (hypophysis) releases nine important peptide hormones
 Hormones bind to membrane receptors & use cAMP as second messenger
Portal Vessels - Blood vessels link two capillary networks
 Entire complex is portal system: ensures that regulatory factors reach intended target
cells before entering general circulation
Two Classes of Hypothalamic Regulatory Hormones
o Releasing hormones (RH) - Stimulate synthesis & secretion of one or more hormones at
anterior lobe
o Inhibiting hormones (IH) - Prevent synthesis & secretion of hormones from anterior lobe
Rate of secretion is controlled by negative feedback
Anterior lobe (adenohypophysis) - Hormones “turn on” endocrine glands or support other organs
1. growth hormone (GH): anabolic hormone, secreted throughout life,  after adolescence
functions: mitosis & promotes protein synthesis
decreased glucose utilization, forces cells to use more fats
mobilization and use of fats;  glucose in blood (diabetic-mimic)
GH-releasing hormone (GH-RH) from hypothalamus causes the release of GH
DISORDERS: A.dwarfism (small in all respects)
B. giantism - most often a pituitary tumor (prior to puberty)
C. acromegaly - also due to tumor (after puberty)
2. thyroid stimulating hormone (TSH): increases # & size of thyroid cells &  T3/T4
Thyrotropin-releasing hormone (TRH) from hypothalamus causes the release of TSH
3. adrenocorticotropic hormone (ACTH): action similar to TSH
Corticotropin-releasing hormone (CRH) from hypothalamus causes the release of ACTH
4./5. gonadotropins: follicle-stimulating hormone (FSH) and luteinizing hormone (LH)
 FSH stimulates follicle development & estrogen secretion by ovaries in females & sperm
production in males
 LH causes ovulation and progesterone production in females and androgen production in males.
Gonadotropin-releasing hormone (GnRH) from hypothalamus causes the release of FSH & LH
6. prolactin (PRL): made in very small amounts - due to prolactin inhibiting factor (same for males)
 high estrogen in pregnancy causes increase in prolactin-releasing hormone
 glandular cells secrete milk
7. melanocyte stimulating hormone (MSH): functional in fetus, kids & pregnant women; stimulates
melanocytes to produce melanin & synthetic form used for "sunless tans"
Posterior lobe (neurohypophysis) contains unmyelinated axons of hypothalamic neurons (from
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 pituitary up to hypothalamus)
Supraoptic & paraventricular nuclei manufacture
8. Antidiuretic hormone (ADH) - targets collecting ducts in kidneys (nephrons) - water retention,
at  levels can cause  in blood pressure * inhibition by alcohol = dehydration
9. Oxytocin (OXT) - targets alveolar cells/mammary glands and uterine myometrium muscle in
females; in males? smooth muscle contraction around prostate--emission?
 transported down axons to be stored in pituitary capillary bed & released on demand
due to appropriate neural stimuli
DISORDERS:diabetes insipidis: A disorder that develops when posterior lobe of pituitary gland
no longer releases adequate amounts of ADH, or when the kidney cannot respond to ADH. What
happens then with this condition to blood pressure?
The Thyroid Gland lies anterior to thyroid cartilage (larynx): consists of 2 lobes with isthmus
Thyroid follicles are hollow spheres lined by cuboidal epithelium; cells surround follicle cavity that
contains viscous colloid & surrounded by network of capillaries that deliver nutrients &
regulatory hormones & accept secretory products and metabolic wastes
Thyroglobulin (Globular Protein) synthesized by follicle cells & secreted into colloid of thyroid
follicles; molecules contain the amino acid tyrosine
o Thyroxine (T4) - also called tetraiodothyronine, contains four iodide ions
o Triiodothyronine (T3)- contains three iodide ions
Thyroid-Stimulating Hormone (TSH) - Absence causes thyroid follicles to become inactive
Neither synthesis nor secretion occurs until TSH binds to membrane receptors and activates key
enzymes in thyroid hormone production
Thyroid Hormones - enter target cells by transport system & affect most cells in body
o Bind to receptors in Cytoplasm, Surfaces of mitochondria & Nucleus
o In children, essential to normal development of
 Skeletal, muscular, and nervous systems
Calorigenic Effect: cell consumes more energy resulting in increased heat generation
 Is responsible for strong, immediate, and short-lived increase in rate of cellular
metabolism
 increased metabolic rate of cells (particularly during embryonic/fetal periods)
 can change Basal Metabolic Rate (BMR) up 2X or down 1/2X
 body burns carbohydrates quickly, then starts on fats with weight loss
 blood pressure (BP) control
 increased rate of heart
 sympathetic nervous system becomes hyperexcited
 great appetite - enhanced GI tract functions
 mineral turnover increases in bone – osteoporosis
DISORDERS:
A. hyperthyroidism due to Grave's disease (autoimmune) & cancer
 Grave's (thyrotoxicosis) = antibody binds to TSH receptors on thyroid cells; burns out tissues,
especially heart (**thyroid storm)
Parathyroid Glands- Embedded in posterior surface of thyroid gland
Parathyroid hormone (PTH) - produced by chief cells in response to low concentrations of Ca 2+
Four Effects of PTH
1. It stimulates osteoclasts and accelerates mineral turnover and releases Ca 2+ from bone
2. It inhibits osteoblasts and reduces rate of calcium deposition in bone
3. It enhances reabsorption of Ca2+ at kidneys, reducing urinary loss
4. It stimulates formation and secretion of calcitriol at kidneys
 Affects complement or enhance PTH
 Enhances Ca2+, PO43- absorption by digestive tract
Adrenal Glands - lie along superior border of each kidney; subdivided into
A. Superficial adrenal cortex: stores lipids, especially cholesterol and fatty acids
 Manufactures steroid hormones: adrenocortical steroids (corticosteroids)
B. Inner adrenal medulla: secretory activities controlled by sympathetic division of ANS
 Produces epinephrine (adrenaline) and norepinephrine
 Metabolic changes persist for several minutes

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Adrenal Cortex - subdivided into three regions:
1. Zona Glomerulosa - outer region of cortex - Produces mineralocorticoids
 For example, aldosterone: stimulates conservation of Na+ & elimination of K+ & increases
sensitivity of salt receptors in taste buds
 Secretion responds to: drop in blood Na +, blood volume, or blood pressure or rise in blood K +
concentration
2. Zona Fasciculata - produces glucocorticoids
 E.g., cortisol (hydrocortisone) with corticosterone; liver converts cortisol to cortisone
 Secretion regulated by negative feedback; has inhibitory effect on production of
Corticotropin-releasing hormone (CRH) in hypothalamus
o ACTH in adenohypophysis accelerates glucose synthesis and glycogen formation
Shows anti-inflammatory effects; inhibits activities of white blood cells & other
components of immune system
3. Zona Reticularis - network of endocrine cells forms narrow band bordering each medulla
 Produces androgens under stimulation by ACTH
Adrenal Medulla - contains two types of secretory cells
1. One produces epinephrine (adrenaline); 75 to 80% of medullary secretions; the other
produces norepinephrine (noradrenaline); 20 to 25% of medullary secretions
DISORDERS:
A. Cushing's disease - tumor of pituitary or adrenals, high level of glucocorticoids; 1 cortisol
 excess mobilization of proteins/fats (excess fat deposition)
 increased gluconeogenesis ** adrenal diabetes
 increased reabsorption of salt and water leads to hypertension
 infections overwhelm
 hyperpigmentation (ACTH ~ MSH, similar effect on melanocytes)
B. Addison's disease - disease, atrophy, autoimmune causes destruction of cortex
 complete failure --> death in 3-5 days mainly due to lack of Na+ and H2O
 hyperpigmentation
 high ACTH because no corticosteroids to negative feedback pituitary
 can have 1 aldosteronism alone or have adrenogenital syndrome alone (tumor)
 results in masculinization in women/ gynecomastia/breast development in men
Pineal Gland: lies in posterior portion of roof of third ventricle; synthesizes hormone melatonin
Functions of Melatonin: inhibiting reproductive functions; protecting against damage by free
radicals & setting circadian rhythms
Pancreas: lies between inferior border of stomach & proximal portion of small intestine: contains
exocrine & endocrine cells
Endocrine Pancreas - consists of cells that form clusters known as pancreatic islets, or islets of
Langerhans; Alpha cells produce glucagon; Beta cells produce insulin; Delta cells produce a
peptide hormone identical to GH-IH; F cells secrete pancreatic polypeptide (PP)
Blood Glucose Levels
When levels  -  cells secrete insulin, stimulating transport of glucose across plasma membranes
When levels  -  cells release glucagon, stimulating glucose release by liver
Insulin is a peptide hormone released by beta cells; causes in target cells
o Accelerates glucose uptake
o Accelerates glucose utilization and enhances ATP production
o Stimulates glycogen formation
o Stimulates amino acid absorption and protein synthesis
o Stimulates triglyceride formation in adipose tissue
Glucagon - released by alpha cells; mobilizes energy reserves & stimulates:
o Breakdown of glycogen in skeletal muscle & liver cells; breakdown of triglycerides in
adipose tissue & production of glucose in liver
DISORDERS:
A. diabetes mellitis - blood glucose >350mg HYPERGLYCEMIA
o fat metabolism accelerated - ketones KETOSIS
o pH down to 7.0 - death in hrs ACIDOSIS
o proteins utilized for energy

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 o glucose in urine ----> water loss POLYURIA
 dehydration ---> thirst; weight loss ---> hunger
type I - insulin-dependant (formerly juvenile): complete lack of insulin; autoimmune disease
 Treatment? insulin pump or injections
 Problem? tissue glucose demands cycle up & down; depends on physical activity, emotional
state, stress
type II - non-insulin dependent (mature onset), however, with increase in population of overweight
children, the number of type II diabetes cases is increasing rapidly at much younger ages.
 >40 years old, >90% of all diabetes * 6.6% of population, 500K new cases/yr
 familial predisposition; insulin inadequate/receptor problem (insulin resistance)
 Symptom? fasting blood sugar level (>80-90mg)
 glucose tolerance (monitored in 12 hr. fasting person consuming 75gm of glucose)
o insulin sensitivity (if adrenal diabetes, a small dose of insulin does NOTHING)
o acetone breath
B. hyperinsulism - overtreatment of diabetes or tumor
o hypoglycemia - as low as 25mg
o hyperexcitability of brain, then depression when blood glucose 50-75mg
o Treatment? glucose, glucagon given when blood glucose down to 70mg
Endocrine Tissues of Other Systems: many other organs also have endocrine functions
1. Intestines: produce hormones important to coordination of digestive activities
2. Kidneys: produce the hormones calcitriol & erythropoietin (EPO) & the enzyme renin
3. Heart: produces natriuretic peptides (ANP & BNP); hen blood volume becomes excessive action
opposes angiotensin II resulting in  in blood volume & blood pressure
4. Thymus: produces thymosins that help develop & maintain normal immune defenses
5. Testes (Gonads): produce androgens in interstitial cells
o Testosterone is the most important male hormone
o Secrete inhibin in nurse cells
o Support differentiation and physical maturation of sperm
6. Ovaries: follicles produce estrogens (primarily estradiol) after ovulation, follicle cells
reorganize into corpus luteum release estrogens & progestins (progesterone)
7. Adipose Tissue Secretions
– Leptin: feedback control for appetite; controls normal levels of GnRH, LH & FSH synthesis
– Resistin: reduces insulin sensitivity
– Estrogen: major source of estrogen in men and post-menopausal women
Hormone Interactions
– Antagonistic (opposing) effects
– Synergistic (additive) effects
– Permissive effects: one hormone is necessary for another to produce effect
– Integrative effects: hormones produce different and complementary results
General Adaptation Syndrome (GAS): how body responds to stress; divided into three phases:
1. Alarm phase: when we are surprised or threatened, we have an immediate physical
reaction, often called the Fight-or-Flight reaction. This prepares the body for life-threatening
situations, channeling away resources from such as the digestive & immune system to more
immediate muscular & emotional needs. This leads to the immune system being depressed, making
us susceptible to disease.
2. Resistance phase: we become used to stress levels, we initially become more resistance to
disease, which leads us to believe we can easily adapt to these more stressful situations. However,
this is only the immune system fighting to keep up with demands and expectations, but requires it
to work at abnormally high levels.
3. Exhaustion phase: eventually reality kicks in and our bodies give up on trying to maintain a
high level of stress. Parts of the body literally start to break down and we become very unwell. If
we continue to fight this situation, we may even die.
Hormone Changes can alter intellectual capabilities, memory, learning & emotional states; affects
behavior when endocrine glands are over-secreting or under-secreting
Aging causes few functional changes; decline in concentration of Growth hormone & Reproductive
hormone