Chapter 17 Endocrine System

Hormone
chemical messenger secreted into bloodstream, stimulates response in another tissue or organ

Target cells
have receptors for hormone

Endocrine glands
produce hormones

Endocrine system
includes hormone producing cells in organs such as brain, heart and small intestine

Endocrine Organs

Major organs of endocrine system

Endocrine vs. Exocrine Glands

Endocrine glands
no ducts, release hormones into tissue fluids, have dense capillary networks to distribute hormones intracellular effects, alter target cell metabolism

Exocrine glands
ducts carry secretion to body surface or other organ cavity extracellular effects (food digestion)

Comparison of Nervous and Endocrine Systems

Communication and adaptation
electrical impulses and neurotransmitters, adapts quickly to continual stimulation hormones in blood, adapts slowly (days to weeks)

Speed and persistence of response

reacts quickly (1 - 10 msec), stops quickly reacts slowly (seconds to days), may continue long after stimulus stops

Area of effect
local, specific effects on target organs general, widespread effects on many organs

Similarities Between Systems

Neuroendocrine cells
neurons that secrete hormones into ECF

Several chemicals function as both neurotransmitters and hormones (norepinephrine) Systems overlapping effects on same target cells Systems regulate each other
neurons trigger hormone secretion hormones stimulate or inhibit neurons

Hypothalamus
Shaped like a flattened funnel, forms floor and walls of third ventricle Regulates primitive functions from water balance to sex drive Many functions carried out by pituitary gland

Pituitary Gland (Hypophysis)

Suspended from hypothalamus by stalk (infundibulum) Location and size
housed in sella turcica of sphenoid bone 1.3 cm diameter

Embryonic Development of Pituitary

Pituitary Gland Anatomy and Hormones of the Neurohypophysis

Hypothalamo-Hypophyseal Portal System

Gonadotropin- releasing hormone controls FSH + LH release Thyrotropin- releasing hormone Corticotropin- releasing hormone Prolactin- releasing factor Prolactin- inhibiting factor GH- releasing hormone GH- inhibiting hormone

Hormones secreted by hypothalamus, travel in portal system to anterior pituitary Hormones secreted by anterior pituitary (under control of hypothalamic releasers and inhibitors)

Pituitary Hormones - Anterior Lobe

Tropic hormones target other endocrine glands
gonadotropins target gonads, FSH (follicle stimulating hormone) and LH (luteinizing hormone) TSH (thyroid stimulating hormone) or thyrotropin ACTH (adrenocorticotropic hormone)

PRL (prolactin) GH (growth hormone )

Anterior Pituitary Hormones

Principle hormones and target organs shown Axis - refers to way endocrine glands interact

Pituitary Hormones Pars Intermedia (pars = part)

Boundary between A and P lobes; 3 cell types Adult human: these cells fuse with anterior lobe Produce POMC (pro-opiomelanocortin) which is processed into ACTH, -MSH and endorphins

Pituitary Hormones - Posterior Lobe

Stores and releases OT and ADH (vasopressin) OT (oxytocin) and ADH produced in hypothalamus, transported down to posterior lobe by hypothalamo-hypophyseal tract

Hormone Actions
FSH
ovaries, stimulates development of eggs and follicles testes, stimulates production of sperm

LH
females, stimulates ovulation and corpus luteum to secrete progesterone males, stimulates interstitial cells of testes to secrete testosterone

ACTH
regulates response to stress, effect on adrenal cortex and secretion of glucocorticoids

Hormone Actions
PRL
female, milk synthesis male, LH sensitivity, thus testosterone secretion

ADH
targets kidneys to water retention ( aquaporins in distal convoluted tubules and collecting ducts), reduce urine also functions as neurotransmitter

Oxytocin
labor contractions, lactation (milk ejection) possible role in sperm transport, emotional bonding

Somatotropin/Growth Hormone
Targets liver to produce somatomedins (mediate somatotropin = GH effects):
mitosis + cellular differentiation for tissue growth protein synthesis
mRNA translated, DNA transciption for mRNA production enhances amino acid transport into cells, catabolism stimulates FFA and glycerol release, protein sparing

lipid metabolism CHO metabolism

glucose sparing effect- glucose stored as glycogen

Electrolyte balance
promotes Na+, K+, Cl- retention, Ca+2 absorption

Growth Hormone
Childhood
bone, cartilage and muscle growth

Adulthood
osteoblastic activity, appositional growth affecting bone thickening and remodeling

Levels of GH
higher during first 2 hours of deep sleep, after high protein meals, after vigorous exercise lower after high CHO meals decline with age

Control of Pituitary: Hypothalamic and Cerebral

Anterior lobe control - releasing hormones and inhibiting hormones of hypothalamus Posterior lobe control - neuroendocrine reflexes
hormone release in response to nervous system signals
suckling infant stimulates nerve endings hypothalamus posterior lobe oxytocin milk ejection

hormone release in response to higher brain centers

milk ejection reflex can be triggered by a baby's cry

Control of Pituitary: Feedback from Target Organs

Negative feedback
target organ hormone levels inhibits release of tropic hormones

Positive feedback
stretching of uterus OT release, causes stretching of uterus OT release, until delivery

Pituitary Disorders
Hypopituitarism
pituitary dwarfism
childhood GH

panhypopituitarism
complete cessation of pituitary secretion causes broad range of disorders

diabetes insipidus (dehydration; no hyperglycemia, nothing to do w/ Glu)

ADH, 10x normal urine output 1) Central DI (low or no ADH); treat with desmopressin (analog) 2) Nephrogenic (inability of kidney) 3) Gestational

Pituitary Disorders
Hyperpituitarism
childhood
gigantism

adult
acromegaly - thickening of bones, soft tissues of hands, feet and face

Pineal Gland
Peak secretion 1-5 yr. olds, by puberty 75% lower Produces serotonin by day, converts it to melatonin at night (darkness hormone; involved in circadian rhythm; regulates sleep) May regulate timing of puberty in humans Melatonin in SAD + PMS, by phototherapy

Pineal gland

Thymus
Location: mediastinum, superior to heart Involution (reduction in size) after puberty Secretes hormones that regulate development and later activation of T-lymphocytes

Thyroid Gland Anatomy

Largest endocrine gland Anterior and lateral sides of trachea 2 large lobes connected by isthmus

Thyroid Gland
Thyroid follicles
filled with colloid and lined with simple cuboidal epith. (follicular cells) that secretes 2 hormones, T3+T4 Thyroid hormone
bodys metabolic rate (protein synthesis and Na+/K+ ATPase activity) and, thus, O2 consumption calorigenic effect - heat production (UCP) heart rate and contraction strength due to permissive action on catecholamines respiratory rate (because need more O2)

Parafollicular cells
produce calcitonin that blood Ca+2, promotes Ca+2 deposition and bone formation, especially in children

Thyroid Gland Disorders

Congenital hypothyroidism ( TH)
infant suffers abnormal bone development, thickened facial features, low temperature, lethargy, brain damage

Myxedema (adult hypothyroidism, TH)

low metabolic rate, sluggishness, sleepiness, weight gain, constipation, dry skin and hair, cold sensitivity, blood pressure and tissue swelling

Endemic goiter (goiter = enlarged thyroid gland)

dietary iodine deficiency, no TH, no - feedback, TSH (trophic effect)

Toxic goiter (Graves disease)

Antibodies activate TSH-R on thyroid gland, TH, ( TSH), exophthalmos

Parathyroid Glands
PTH
blood Ca+2
absorption urinary excretion osteoblast activity

Absence of glands (DiGeorge syndrome) Hypoparathyroid

surgical excision fatal tetany (muscle spasms) 3-4 days

Hyperparathyroid
tumor; causes soft, fragile and deformed bones, blood Ca+2, renal calculi

Adrenal Gland

Adrenal Medulla
Sympathetic ganglion innervated by sympathetic preganglionic fibers
stimulation causes release of (nor-)epinephrine (catecholamines) Chromaffin cells found in the medulla (and elsewhere) are neuroendocrine cells = secrete their neurotransmitter into systemic circulation instead of into a specific target organ/tissue Epinephrine (norEpi has no Me group)

Adrenal Cortex
3 layers
(outer) zona glomerulosa, (middle) zona fasciculata, (inner) zona reticularis

Corticosteroids
mineralocorticoids (zona glomerulosa)
control electrolyte balance, aldosterone promotes Na+ retention and K + excretion part of the renin-angiotensin system

glucocorticoids (zona fasciculata - response to ACTH)

especially cortisol, which: - stimulates fat + protein catabolism, - gluconeogenesis (from a.a.s + FAs) and release of fatty acids and glucose into blood to repair damaged tissues; counteracts insulin - enhances epinephrine vasoconstrictive effects - suppresses immune system ( inflammation)

sex steroids (zona reticularis)

androgens, including DHEA (other tissues convert to testosterone) and estrogen (important after menopause)

Adrenal Disorders
Pheochromocytoma tumor of adrenal medulla, with hypersecretion of (nor-)epinephrine Extra-chromaffin tissue that didnt involute after birth causes HR, hypertension (vasoconstriction), metabolic rate, hyperglycemia, glycosuria, nervousness, indigestion, sweating (diaphoresis) Cushing syndrome (70% due to pituitary tumor = adenoma excess ACTH excess cortisol; 30% due to adrenal gland tumor) causes hyperglycemia (from gluconeogenesis and insulin resistance), hypertension (cortisol enhances epinephrines vasoconstrictive effects), weakness, edema muscle, bone loss with fat deposition shoulders + face (central obesity)

Adrenogenital Syndrome (AGS)

Androgen hypersecretion causes enlargement of penis or clitoris and premature onset of puberty. Prenatal AGS in girls can result in masculinized genitals (photo) AGS in women can result in deep voice, beard, body hair

Addison Disease
Hyposecretion (mnemonic: add more) of glucocorticoids and mineralocorticoids by adrenal cortex Hypoglycemia (since cortisol), Na+ and K+ imbalances, dehydration, hypotension (since aldosterone), weight loss, weakness Causes pituitary ACTH secretion (negative feedback), stimulates melanin synthesis (from -MSH production) and bronzing of skin

Pancreas

Retroperitoneal, inferior and dorsal to stomach

Pancreatic Hormones
Mostly exocrine gland with pancreatic islets of endocrine cells that produce: Insulin (from -cells)
peptide hormone secreted after meal with carbohydrates (raises glucose blood levels) stimulates glucose and amino acid uptake nutrient storage effect (stimulates glycogen, fat and protein synthesis counteracts glucagon insulin-glucagon buffer glucose levels

Pancreatic Hormones
Glucagon (from cells of the islets of Langerhans)
secreted in very low carbohydrate and high protein diet or fasting stimulates glycogenolysis, lipolysis and release of FFAs, promotes absorption of amino acids for gluconeogenesis binds to glucagon receptors in the liver

Somatostatin (GH-inhibiting hormone, from cells)

secreted with rise in blood glucose and amino acids after a meal paracrine secretion- modulates secretion of + cells

Somatostatin
Produced by: Neuroendocrine cells in the PVN, counteracts GHRH by inhibiting GH release in pituitary -cells of the pancreas, inhibits insulin and glucagon release; inhibits H+ secretion by parietal cells in the stomach

Diabetes Mellitus
Signs and symptoms
polyuria, polydipsia, polyphagia hyperglycemia, glycosuria, ketonuria
osmotic diuresis : blood glucose levels rise above transport maximum of kidney tubules, glucose remains in urine, osmolarity and draws water into urine

Type I (IDDM) - 10%

some cases have autoimmune destruction of cells, diagnosed about age 12 treated with diet, exercise, monitoring of blood glucose and periodic injections of insulin or insulin pump

Diabetes Mellitus
Type II (NIDDM) - 90%
insulin resistance
failure of target cells to respond to insulin

3 major risk factors are heredity, age (40+) and obesity treated with weight loss program of diet and exercise, oral medications improve insulin secretion or target cell sensitivity

Pathology of Diabetes
Acute pathology: cells cannot absorb glucose, rely on fat and proteins (weight loss + weakness)
fat catabolism: FFAs in blood and ketone bodies ketonuria promotes osmotic diuresis, loss of Na+ + K+ ketoacidosis occurs, as ketones blood pH (and hyperventilation)
if continued, causes dyspnea and eventually diabetic coma

Chronic pathology
chronic hyperglycemia leads to neuropathy, pancreatic failure, cardiovascular damage
retina and kidneys (common in type I), atherosclerosis leading to heart failure (common in type II), and gangrene

Hyperinsulinism
From excess insulin injection or pancreatic islet tumor Causes hypoglycemia, weakness and hunger
triggers secretion of epinephrine, GH (glucose sparing) and glucagon
GH also increases the number of adrenergic receptors on cardiac muscle, epinerphrine sensitivity, HR side effects: anxiety, sweating and HR

Insulin shock
uncorrected hyperinsulinism with disorientation, convulsions or unconsciousness

Histology of Ovary

Ovary
Granulosa cells (look like granules): wall of ovarian follicle
produces estradiol, first half of menstrual cycle

Corpus luteum: follicle after ovulation

produces progesterone for 12 days or several weeks with pregnancy (progestational steroidal ketone)

Functions
development of female reproductive system and physique regulate menstrual cycle, sustain pregnancy prepare mammary glands for lactation

Both secrete inhibin: suppresses FSH, but not LH release (in pituitary)

Histology of Testis

Germinal epithelium of the testicle

1: basal lamina 2: spermatogonia (2n) 3: primary spermatocyte (2n)
undergoes meiosis I

4: secondary spermatocyte (n) 5: spermatid (n) 6: mature spermatid (n) 7: Sertoli cell 8: tight junction (blood testis barrier)

Testes
Interstitial cells (Leydig cells) (between seminiferous tubules)
produce testosterone in response to LH (Leydig hormone)

Functions
development of male reproductive system and physique sustains sperm production and sex drive

Sustentacular cells (Sertoli cells)

sustain, nourish the sperm secrete inhibin: suppresses FSH secretion, stabilizes sperm production rates

Endocrine Functions of Other Organs

Heart - atrial natriuretic factor (ANF)
Na+ and, thus H2O loss by kidneys blood volume + BP

Kidneys

calcitriol (active vit. D) - Ca+2 absorption in intestine, reabsorption in kidney; bone resorption; phosphate excretion erythropoietin - stimulates bone marrow to produce RBCs gastrin: secreted by G cells of duodenum, stomach and pancreas; stimulates parietal cells secretin: by G cells, stimulates bicarbonate production by pancreas CCK: released in response to fats in duodenum, stimulates bile release from gallbladder and secretion of pancreatic juices coordinate digestive motility and secretion

Stomach and small intestines - enteric hormones

Endocrine Functions of Other Organs

Liver
angiotensinogen (a prohormone)
precursor of angiotensin II, a vasoconstrictor

erythropoietin (15%) somatomedins (aka IGFs) - mediate action of GH (aka somatotropin)

Placenta
secretes estrogen, progesterone and others
regulate pregnancy, stimulate development of fetus and mammary glands

Hormone Chemistry
Steroids
derived from cholesterol
sex steroids, corticosteroids

Peptides and glycoproteins

all releasing and inhibiting hormones of hypothalamus most of anterior pituitary hormones OT, ADH

Monoamines (biogenic amines)

derived from tyrosine
catecholamines (norepinephrine, epinephrine, dopamine) and thyroid hormones

Hormone Transport
Transport proteins (albumins and globulins)
steroids and thyroid hormone are hydrophobic and must bind to transport proteins for transport bound hormone - hormone attached to transport protein, (half-life hours to weeks, protects from enzymes and kidney filtration) only unbound hormone can leave capillary to reach target cell (half-life a few minutes)

Hormone Transport & Action

Steroids and thyroid hormone require transport protein, but easily enter cell Monoamines and peptides transport easily in blood, but cannot enter cell and must bind to receptors

Hormone Receptors
Located on plasma membrane, mitochondria and other organelles, or in nucleus Usually thousands for given hormone
turn metabolic pathways on or off when hormone binds

Exhibit specificity and saturation

Steroid Hormones

Synthesized from cholesterol

Steroid Hormones
Hydrophobic, depend on transport proteins, long lasting effects Enter target cells easily, enter nucleus and bind to receptor associated with DNA Receptor has 3 regions
one binds the hormone one binds to acceptor site on chromatin one activates DNA transcription
leads to synthesis of proteins, alter metabolism of target cells

Peptides
Synthesis
preprohormone - has leader sequence, guides it to RER which removes leader sequence, now its called a prohormone - RER transfers it to Golgi complex, may modify it, then packages it for secretion

Insulin Synthesis
Begins as preproinsulin the leader sequence is removed, chain folds, 3 disulfide bridges form and called Proinsulin, in Golgi C peptide removed leaving Insulin

cAMP as Second Messenger

1) Hormone binds activates G protein 2) Activates adenylate cyclase 3) Produces cAMP 4) Activates kinases 5) Activates enzymes 6) Metabolic reactions

Hormone Action, Other 2nd & 3rd Messengers

Monoamines
Synthesized from tyrosine, mostly hydrophilic, activate second messenger systems TH only one made from 2 tyrosine molecules whats important is measuring the amount of free (unbound) T3 / T4 ratio. T3 (triidothyronine) is more potent than T4 , but there is more of the latter in blood (later it is converted by deiodinases) permissive effect on catecholamines

Thyroid hormone synthesis

Thyroid Hormone Synthesis

(1) I- transported into cell then (2) I- + thyroglobulin released into lumen (3-5 next slide) (6)TSH stimulates pinocytosis, lysosome liberates TH, carried by thyroxine-binding globulin

Thyroid Hormone Synthesis

Thyroid Hormone Action

TH binds to receptors on mitochondria (metabolic rate), ribosomes and chromatin (protein synthesis) calorigenic effect (UCP)

Enzyme Amplification

Regulation of Cell Sensitivity to a Hormone

Hormone Interactions
Most cells sensitive to more than one hormone and exhibit interactive effects Synergistic effects Permissive effects
one hormone enhances response to a second hormone

Antagonistic effects

Stress and Adaptation

Any situation that upsets homeostasis and threatens ones physical or emotional well-being causes stress The way body reacts to stress is called the general adaptation syndrome, occurs in 3 stages
alarm reaction stage of resistance stage of exhaustion

Alarm Reaction
Initial response epinephrine and norepinephrine levels HR (stimulation of SA, AVN nodes etc.) and BP (MAP = COR = HRSVR) blood glucose levels Sodium and water retention (aldosterone)

Stage of Resistance
After a few hours, glycogen reserves gone ACTH/cortisol levels Fat and protein breakdown Gluconeogenesis Depressed immune function Susceptibility to infection and ulcers

Stage of Exhaustion
Stress that continues until fat reserves are gone Protein breakdown and muscle wasting Loss of glucose homeostasis Hypertension and electrolyte imbalances (loss of K+ and H+) Hypokalemia and alkalosis leads to death

Paracrine Secretions
Chemical messengers that diffuse short distances and stimulate nearby cells
unlike neurotransmitters not produced in neurons unlike hormones not transported in blood

Eicosanoids
an important family of paracrine secretions

Eicosanoids (paracrine action)

Derived from arachidonic acid
released from plasma membrane, 2 enzymes convert it lipoxygenase
converts arachidonic acid to leukotrienes that mediate allergic and inflammatory reactions (blocked by cortisol which thus inflammation)

cyclooxygenase
converts arachidonic acid to
prostacyclin: produced by blood vessel walls, inhibits blood clotting and causes vasodilation thromboxanes: produced by blood platelets after injury, they override prostacyclin and stimulate vasoconstriction and clotting prostaglandins: diverse group including PGEs: relaxes smooth muscle in bladder, intestines, bronchioles, uterus and stimulates contraction of blood vessels PGFs: opposite effects

Eicosanoid Synthesis