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• 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
Chapter 17 Endocrine System
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Endocrine Organs
• Major organs of endocrine system
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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)
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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
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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
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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
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Pituitary Gland (Hypophysis)
• Suspended from hypothalamus by stalk (infundibulum)
• Location and size– housed in sella turcica of sphenoid bone– 1.3 cm diameter
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Embryonic Development of Pituitary
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Pituitary Gland Anatomy and Hormones of the Neurohypophysis
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Gonadotropin- releasing hormone controls FSH + LH releaseThyrotropin- releasing hormoneCorticotropin- releasing hormoneProlactin- releasing factorProlactin- inhibiting factorGH- releasing hormoneGH- inhibiting hormone
Hypothalamo-Hypophyseal Portal System
• Hormones (red box)secreted by anterior pituitary (under control of hypothalamic releasers and inhibitors)
• Hormones secreted by hypothalamus, travel in portal system to anterior pituitary
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• Tropic hormones target other endocrine glands– gonadotropins target gonads, FSH (follicle stimulating
hormone) and LH (luteinizing hormone)– TSH (thyroid stimulating hormone)– ACTH (adrenocorticotropic hormone)
• PRL (prolactin)
• GH (growth hormone )
Pituitary Hormones - Anterior Lobe
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Anterior Pituitary Hormones
• Principle hormones and target organs shown• Axis - refers to way endocrine glands interact
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• Adult human these cells fuse with anterior lobe
• Produce POMC (pro-opiomelanocortin) which is processed into ACTH and endorphins
Pituitary Hormones - Pars Intermedia
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• Stores and releases OT and ADH
• OT (oxytocin) and ADH produced in hypothalamus, transported down to posterior lobe by hypothalamo-hypophyseal tract
Pituitary Hormones - Posterior Lobe
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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
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• PRL– female, milk synthesis– male, LH sensitivity, thus testosterone secretion
• ADH– targets kidneys to water retention, reduce urine– also functions as neurotransmitter
• Oxytocin– labor contractions, lactation– possible role sperm transport, emotional bonding
Hormone Actions 2
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• Targets liver to produce somatomedins mitosis + cellular differentiation for tissue growth– protein synthesis
• mRNA translated, DNA transciption for mRNA production
• enhances amino acid transport into cells, catabolism
– lipid metabolism • stimulates FFA and glycerol release, protein sparing
– CHO metabolism• glucose sparing effect- glucose stored as glycogen
– Electrolyte balance• promotes Na+, K+, Cl- retention, Ca+2 absorption
Growth Hormone
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• 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
Growth Hormone 2
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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
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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
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Pituitary Disorders
• Hypopituitarism– pituitary dwarfism
• childhood GH
– panhypopituitarism• complete cessation of pituitary
secretion
• causes broad range of disorders
– diabetes insipidus ADH, 10x normal urine output
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• Hyperpituitarism– childhood
• gigantism
– adult• acromegaly - thickening of bones, soft tissues of hands, feet
and face
Pituitary Disorders
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Pineal Gland
• Peak secretion 1-5 yr. olds, by puberty 75% lower• Produces serotonin by day, converts it to melatonin
at night• May regulate timing of puberty in humans• Melatonin in SAD + PMS, by phototherapy
Pineal gland
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Thymus
• Location: mediastinum, superior to heart
• Involution after puberty
• Secretes hormones that regulate development and later activation of T-lymphocytes
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Thyroid Gland Anatomy
• Largest endocrine gland• Anterior and lateral sides of trachea• 2 large lobes connected by isthmus
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Thyroid Gland
• Thyroid follicles– filled with colloid and lined with simple cuboidal
epith. (follicular cells) that secretes 2 hormones, T3+T4
– Thyroid hormone body’s metabolic rate and O2 consumption
• calorigenic effect - heat production heart rate and contraction strength respiratory rate
• Parafollicular cells– produce calcitonin that blood Ca+2, promotes Ca+2
deposition and bone formation especially in children
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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
• Toxic goiter (Graves disease)– antibodies mimic TSH, TH, exophthalmos
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Parathyroid Glands
• PTH blood Ca+2
absorption urinary excretion
• bone resorption
• Hypoparathyroid– surgical excision– fatal tetany 3-4 days
• Hyperparathyroid – tumor; causes soft, fragile and deformed
bones, blood Ca+2, renal calculi
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Adrenal Gland
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Adrenal Medulla
• Sympathetic ganglion innervated by sympathetic preganglionic fibers – stimulation causes release of (nor-)epinephrine
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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
– glucocorticoids (zona fasciculata - response to ACTH)• especially cortisol, stimulates fat + protein catabolism,
gluconeogenesis (from a.a.’s + FA’s) and release of fatty acids and glucose into blood to repair damaged tissues
– sex steroids (zona reticularis)• androgens, including DHEA (other tissues convert to
testosterone) and oestrogen (important after menopause)
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Adrenal Disorders
• Pheochromocytoma– tumor of adrenal medulla, with hypersecretion of
(nor-)epinephrine– causes BP, metabolic rate, hyperglycemia,
glycosuria, nervousness, indigestion, sweating
• Cushing syndrome (adrenal tumor, excess ACTH)– causes hyperglycemia, hypertension, weakness, edema– muscle, bone loss with fat deposition shoulders + face
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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
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Addison Disease
• Hyposecretion of glucocorticoids and mineralocorticoids by adrenal cortex
• Hypoglycemia, Na+ and K+ imbalances, dehydration, hypotension, weight loss, weakness
• Causes pituitary ACTH secretion, stimulates melanin synthesis and bronzing of skin
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Pancreas
• Retroperitoneal, inferior and dorsal to stomach
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Pancreatic Hormones
• Mostly exocrine gland with pancreatic islets of endocrine cells that produce:
• Insulin (from cells)– secreted after meal with carbohydrates raises glucose
blood levels– stimulates glucose and amino acid uptake– nutrient storage effect (stimulates glycogen, fat and
protein synthesis– antagonizes glucagon
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Pancreatic Hormones 2
• Glucagon (from cells)– secreted in very low carbohydrate and high protein diet
or fasting– stimulates glycogenolysis, fat catabolism (release of
FFA’s) and promotes absorption of amino acids for gluconeogenesis
• Somatostatin (growth hormone-inhibiting hormone, from delta () cells)– secreted with rise in blood glucose and amino acids
after a meal– paracrine secretion- modulates secretion of + cells
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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
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Diabetes Mellitus 2
• 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
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Pathology of Diabetes
• Acute pathology: cells cannot absorb glucose, rely on fat and proteins (weight loss + weakness)– fat catabolism FFA’s in blood and ketone bodies– ketonuria promotes osmotic diuresis, loss of Na+ + K+
– ketoacidosis occurs as ketones blood pH• if continued causes dyspnea and eventually diabetic coma
• Chronic pathology– chronic hyperglycemia leads to neuropathy and
cardiovascular damage• retina and kidneys (common in type I), atherosclerosis
leading to heart failure (common in type II), and gangrene
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Hyperinsulinism
• From excess insulin injection or pancreatic islet tumor
• Causes hypoglycemia, weakness and hunger– triggers secretion of epinephrine, GH and glucagon
• side effects: anxiety, sweating and HR
• Insulin shock– uncorrected hyperinsulinism with disorientation,
convulsions or unconsciousness
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Histology of Ovary
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Ovary
• Granulosa cells: wall of ovarian follicle– produces oestradiol, first half of menstrual cycle
• Corpus luteum: follicle after ovulation– produces progesterone for 12 days or several weeks
with pregnancy
• Functions– development of female reproductive system and
physique– regulate menstrual cycle, sustain pregnancy– prepare mammary glands for lactation
• Both secrete inhibin: suppresses FSH secretion
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Histology of Testis
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Testes
• Interstitial cells (between seminiferous tubules)– produce testosterone
• Functions– development of male reproductive system and physique– sustains sperm production and sex drive
• Sustentacular cells– secrete inhibin: suppresses FSH secretion, stabilizes
sperm production rates
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Endocrine Functions of Other Organs
• Heart - atrial natriuretic factor blood volume + BP, from Na+ and H2O loss by
kidneys
• Kidneys– calcitriol - Ca+2 and phosphate: absorption, loss for
bone deposition– erythropoietin - stimulates bone marrow to produce
RBC’s
• Stomach and small intestines - enteric hormones– coordinate digestive motility and secretion
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Endocrine Functions of Other Organs 2
• Liver– angiotensinogen (a prohormone)
• precursor of angiotensin II, a vasoconstrictor
– erythropoietin (15%)– somatomedins - mediate action of GH
• Placenta– secretes oestrogen, progesterone and others
• regulate pregnancy, stimulate development of fetus and mammary glands
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Hormone Chemistry• Steroids
– derived from cholesterol• sex steroids, corticosteroids
• Monoamines (biogenic amines)– derived from tyrosine
• catecholamines (norepinephrine, epinephrine, dopamine) and thyroid hormones
• Peptides and glycoproteins– OT, ADH; all releasing and
inhibiting hormones of hypothalamus; most of anterior pituitary hormones
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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)
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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
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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
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Steroid Hormones
• Synthesized from cholesterol
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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
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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
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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
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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
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Hormone Action, Other 2nd & 3rd Messengers
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Monoamines
• Synthesized from tyrosine, mostly hydrophilic, activate second messenger systems
• TH only one made from 2 tyrosine molecules
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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
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Thyroid Hormone Synthesis
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Thyroid Hormone Action• TH binds to
receptors on mitochondria (metabolic rate), ribosomes and chromatin ( protein synthesis)
• One protein produced: Na+-K+ ATPase generates heat
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Enzyme Amplification
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Regulation of Cell Sensitivity to a Hormone
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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
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Stress and Adaptation
• Any situation that upsets homeostasis and threatens one’s physical or emotional well-being causes stress
• Way body reacts to stress called the general adaptation syndrome, occurs in 3 stages– alarm reaction– stage of resistance– stage of exhaustion
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Alarm Reaction
• Initial response epinephrine and norepinephrine levels HR and BP blood glucose levels
• Sodium and water retention (aldosterone)
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Stage of Resistance
• After a few hours, glycogen reserves gone ACTH and cortisol levels
• Fat and protein breakdown
• Gluconeogenesis
• Depressed immune function
• Susceptibility to infection and ulcers
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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
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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
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Eicosanoids• Derived from arachidonic acid
– released from plasma membrane, 2 enzymes convert it– lipoxygenase
• converts arachidonic acid to leukotrienes that mediate allergic and inflammatory reactions
– cyclooxygenase • converts arachidonic acid to
– prostacyclin: produced by blood vessel walls, inhibits blood clotting and vasoconstriction
– thromboxanes: produced by blood platelets after injury, they override prostacyclin and stimulate vasoconstriction and clotting
– prostaglandins: diverse group including
» PGE’s: relaxes smooth muscle in bladder, intestines, bronchioles, uterus and stimulates contraction of blood vessels
» PGF’s: opposite effects
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Eicosanoid Synthesis