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Chapter 11

Endocrine Glands Secretion & Action of Hormones


Endocrine Glands

• Are ductless & secrete hormones into bloodstream • Hormones go to target cells that contain receptor proteins for it • Neurohormones are secreted into blood by specialized neurons • Hormones affect metabolism of targets

Fig 11.1


Chemical Classification of Hormones
• Amine hormones are derived from tyrosine or tryptophan – Include NE, Epi, thyroxine, melatonin • Polypeptide/protein hormones are chains of amino acids – Include ADH, GH, insulin, oxytocin, glucagon, ACTH, PTH • Glycoproteins – Long polypeptide bound to a carbohydrate group – Include LH, FSH, TSH • Steroids are lipids derived from cholesterol – Include testosterone, estrogen, progesterone & cortisol


Common Aspects of Neural & Endocrine Regulation • Both NS & endocrine system use chemicals to communicate • Difference between NTs & hormones is transport in blood & more diversity of effects in hormone targets • Some chemicals are used as hormones & NTs • Targets for both NTs & hormones must have specific receptor proteins • Must be way to rapidly inactivate both 11-12 .

Hormone Interactions
• A tissue usually responds to # of hormones • 2 hormones are synergistic if work together to produce an effect
– Produce a larger effect together than individual effects added together – Effects of Epi and NE on heart rate

• A hormone has permissive effect if it enhances responsiveness of a target organ to 2nd hormone • If action of 1 hormone inhibits effect of another, it is antagonistic

Hormone Levels & Tissue Responses
• Half-life is time required for blood level to be reduced by half
– Ranges from mins to hrs for most (days for thyroid hormones)

• Normal tissue responses are produced only when hormones are in physiological range • High (pharmacological) doses can cause # of side effects
– Probably by binding to receptors of other hormones

Hormone Levels & Tissue Responses continued
• Priming effect (upregulation) occurs when a hormone induces more of its own receptors in target cells
– Results in greater response in target cell

• Desensitization (downregulation) occurs after long exposure to high levels of polypeptide hormone
– Subsequent exposure to this hormone produces a lesser response – Due to decrease in # of receptors on targets – Most peptide hormones have pulsatile secretion which prevents downregulation


Mechanisms of Hormone Action 11-16 .

& low capacity for a hormone • Lipid hormones have receptors in target's cytoplasm &/or nucleus because can diffuse thru plasma membrane • Receptors for water-solubles are on surface of target cell 11-17 . high affinity.Mechanisms of Hormone Action • Target cell receptors show specificity.

Hormones That Bind to Nuclear Receptor Proteins • Lipid hormones travel in blood attached to carrier proteins – They dissociate from carriers to pass thru plasma membrane of target • Receptors are called nuclear hormone receptors Fig 11.4 11-18 .

Nuclear Hormone Receptors • Serve as transcription factors when bound to hormone ligands – Activate transcription • Constitute a "superfamily" composed of steroid family & thyroid hormone family (which includes vitamin D & retinoic acid) 11-19 .

Nuclear Hormone Receptors • Have ligand (hormone)-binding & DNA-binding domains – Binds hormone & translocates to nucleus – Binds to hormone-response element (HRE) on DNA located adjacent to target gene Fig 11.5 11-20 .

Fig.6 . 11.

Mechanism of Thyroid Hormone Action continued • T3 & receptor bind to 1 half-site • Other half-site binds retinoic acid – Two partners form heterodimer that activates HRE • Stimulates transcription of target gene Fig 11.7 11-23 .

Hormones That Use 2nd Messengers • Water soluble hormones use cell surface receptors because cannot pass through plasma membrane – Actions are mediated by 2nd messengers – Hormone is extracellular signal. 2nd messenger carries signal from receptor to inside of cell 11-24 .

8 11-25 .Adenylate Cyclase-cAMP • Mediates effects of many polypeptide & glycoprotein hormones • Hormone binds to receptor causing dissociation of a G-protein subunit Fig 11.

8 11-26 .Adenylate Cyclase-cAMP continued • G-protein subunit binds to & activates adenylate cyclase – Which converts ATP into cAMP • cAMP attaches to inhibitory subunit of protein kinase Fig 11.

activating protein kinase Which phosphorylates enzymes that produce hormone’s effects cAMP inactivated by phosphodiesterase Fig 11.8 11-27 .Adenylate Cyclase-cAMP continued – – – Inhibitory subunit dissociates.


Pituitary Gland 11-34 .

16 11-35 .Pituitary Gland • Pituitary gland is located beneath hypothalamus at base of forebrain Fig 8.

Pituitary Gland continued • Is structurally & functionally divided into anterior & posterior lobes • Hangs below hypothalamus by infundibulum • Anterior produces own hormones – Controlled by hypothalamus • Posterior stores & releases hormones made in hypothalamus Fig 11.12 11-36 .

Anterior Pituitary • Secretes 6 trophic hormones that maintain size of targets – High blood levels cause target to hypertrophy • Low levels cause atrophy 11-37 .

& movement of amino acids into cells • Thyroid stimulating hormone (TSH) stimulates thyroid to produce & secrete T4 & T3 • Adrenocorticotrophic hormone (ACTH) stimulates adrenal cortex to secrete cortisol.Anterior Pituitary continued • Growth hormone (GH) promotes growth. aldosterone • Follicle stimulating hormone (FSH) stimulates growth of ovarian follicles & sperm production • Luteinizing hormone (LH) causes ovulation & secretion of testosterone in testes • Prolactin (PRL) stimulates milk production by mammary glands 11-38 . protein synthesis.

Anterior Pituitary continued • Release of Anterior Pituitary hormones is controlled by hypothalamic releasing & inhibiting factors & by feedback from levels of target gland hormones 11-39 .

• Diffuse into A. Pit.15 11-40 . & regulate secretion of its hormones Fig 11.Anterior Pituitary continued • Releasing & inhibiting hormones from hypothalamus are released from axon endings into capillary bed in median eminence – Carried by hypothalamohypophyseal portal system directly to another capillary bed in A. Pit.

• Involves short feedback loop in which retrograde flow of blood & hormones from A. estrogen stimulates “LH surge” by positive feedback Feedback Control of Anterior Pituitary Fig 11. to hypothalamus inhibits secretion of releasing hormone • Involves negative feedback of target gland hormones • & during menstrual cycle.17 11-41 . Pit.

psychological stress affects circadian rhythms. menstrual cycle.g. Pit. & adrenal hormones 11-42 . secretion – E.Higher Brain Function & Anterior Pituitary Secretion • Hypothalamus receives input from higher brain centers that can affect A.

from hypothalamus • Follows a circadian pattern--is greater during sleep & lower during waking hours • Stimulates growth in children & adolescents • Has important metabolic effects in adults – Is stimulated by increased blood amino acids & decreased blood glucose – Is increased during fasting – Stimulates protein synthesis. & inhibited by somatostatin. stimulated by GHRH. & decreases glucose use by most tissues 19-61 . fat breakdown.Growth Hormone Secretion • Is from anterior pituitary.

Growth Hormone (GH or somatotropin) • Stimulates uptake of amino acids. growth in most tissues. protein synthesis. • Stimulates breakdown of fats to be used as an energy source but stimulates synthesis of glycogen: glucose sparing (diabetogenic) • Promotes bone and cartilage growth • Regulates blood levels of nutrients after a meal and during periods of fasting • Stimulates glucose synthesis by liver .

metabolic effects) 19-62 . produced by many tissues • Are called somatomedins because mediate many of GH's effects • Liver produces & secretes IGF-1 in response to GH – IGF-1 in turn stimulates cell division & growth of cartilage • These actions are supported by IGF-2 which has more insulinlike actions • Do not mediate effects of GH on lipolysis & glucose sparing (i.e.Insulin-like Growth Factors (IGFs) • Are similar to pro-insulin.

6 .Metabolic Action of Growth Hormone Figure 16.

Growth Hormone & Body Growth • Growth of skeleton occurs first as growth of cartilage at epiphyseal discs which then become converted to bone – Mediated by IGF-1 & 2 which stimulate chondrocytes to divide & secrete more cartilaginous matrix – Growth stops when epiphyseal discs are ossified • Gigantism produced by excess GH secretion in children • Dwarfism caused by inadequate secretion of GH during childhood 19-64 .

Growth Hormone & Body Growth • Excess GH secretion in adults. after epiphyseal discs are ossified. deformities in hands.18 19-65 . feet. & bones of face Fig 19. results in acromegaly – There is no increase in height – However soft tissue still grows • Causing elongation of jaw.

Growth Hormone Stimulation: functions in regulating growth. increased synthesis of proteins in skeletal muscle. e.g. bone. Stimulate growth in cartilage. insulinlike growth factors (IGF’s) – Insulinlike growth factors: bind to receptors on membranes of target cells.. . metabolism GHRH from hypothalamus causes release of… Growth hormone from anterior pituitary effects… Target tissues: most tissues of the body • Direct effect: GH binds to receptors on cells and causes changes within the cells. tissue maintenance. Increased lipolysis and decreased use of glucose for energy • Indirect effect: causes liver and skeletal muscle to produce somatomedins.

GHRH and GHIN travel via the hypothalamo-hypophyseal portal system to ant. pituitary 3. GH acts on target tissues. Increasing GH levels have neg feedback effect on hypothala. . Increased GHRH and reduced GHIH act on AP and result in increased GH secretion. 4. 2. Stress and decreased glucose levels increase release of GHRH and decreased release of GHIH. 5.Regulation of GH Secretion 1.

• Hyposecretion of GH may result in dwarfism • Hypersecretion may result in giantism or acromegaly depending on ossification of epiphyseal plates . • GHRH secretion in response to low blood glucose. levels lower at other times of day. increase in certain a.a. • Peak GH levels during deep sleep.Growth Hormone: Inhibition • Hypothalamus produces growth hormone inhibiting hormone (GHIH = somatostatin) • Inhibits production of GH by anterior pituitary. stress. • GHIH secretions in response to high blood glucose.

Posterior Pituitary • Stores & releases 2 hormones produced in hypothalamus: – Antidiuretic hormone (ADH/vasopressin) which promotes H20 conservation by kidneys – Oxytocin which stimulates contractions of uterus during parturition • & contractions of mammary gland alveoli for milk-ejection reflex 11-43 .

Hypothalamic Control of Posterior Pituitary
• Supraoptic nuclei of hypothalamus produce ADH • Paraventricular nuclei produce oxytocin • Both transported along hypothalamo-hypophyseal tract to posterior pituitary • Release controlled in hypothalamus by neuroendocrine reflexes
Fig 11.13

Thyroid Gland


Thyroid Gland

• Is located just below the larynx • Secretes T4 & T3 which set BMR & are needed for growth, development

a protein-rich fluid 11-53 .Thyroid Gland • Consists of microscopic thyroid follicles – Outer layer is follicle cells that synthesize T4 – Interior filled with colloid.

23 11-54 .Production of Thyroid Hormones • Iodide (I-) in blood is actively transported into follicles & secreted into colloid – Where it is oxidized to iodine (I2) & attached to tyrosines of thyroglobulin • A large storage molecule for T4 & T3 • TSH stimulates hydrolysis of T4 & T3s from thyroglobulin & then secretion Fig 11.

fat. boundthyroxine serves as a reservoir of this hormone – 33-40% of T4 converted to T3 in cells: T3 more potent – Bind with intracellular receptor molecules and initiate new protein synthesis – Increase rate of glucose. – Only free thyroxine and T3 can enter cells. .6% of thyroxine in the blood is bound to thyroxinebinding globulin (TBG) from the liver. Rest is free. amt of free unbound T3 in plasma is 10x’s greater than free T4. – TBG has a higher affinity for T4 than for T3. protein metabolism in many tissues thus increasing body temperature – Normal growth of many tissues dependent on presence of thyroid hormones.Thyroid Hormones • Produced by follicular cells • Triiodothyronine or T3 -less produced • Tetraiodothyronine or T4 or thyroxine-more – 99.

Maintain normal rate of metabolism. and nervous tissue require thyroid hormone.4 for effects of hypo. 5.. and protein are metabolized. Can alter the number and activity of mitochondria resulting in greater ATP synthesis and heat production. Increase the activity of Na+-K+ pump which increases body temperature (“calorigenic effect”) 4. fat. Normal growth and maturation of bone. 2. teeth. Both T3 and T4 play a permissive role for GH and GH does not have its normal effect on tissues if T3 and T4 are lacking. Increase the rate at which glucose.and hypersecretion . hair. 6. See Table 18.t. c. 3. 7.Effects of T3 and T4 1.

Goiter • In absence of sufficient dietary iodide.Diseases of the Thyroid . thyroid gland grows • Resulting in a goiter Fig 11.25 11-55 . T4 & T3 cannot be made & levels are low – Low T4 & T3 don’t provide negative feedback & TSH levels go up • Because TSH is a trophic hormone.

cold intolerance – & myxedema = puffy face.Diseases of the Thyroid . weight gain. lethargy. feet – During fetal development hypothyroidism can cause cretenism (severe mental retardation) 11-56 . hands.Hypothyroidism • People with inadequate T4 & T3 levels are hypothyroid – Have low BMR.

weight loss. high BMR 11-57 . irritability. heat intolerance.Diseases of the Thyroid .Hyperthyroidism • Goiters are also produced by Grave's disease – Autoimmune disease where antibodies act like TSH & stimulate thyroid gland to grow & oversecrete = hyperthyroidism • Characterized by exopthalmos.

11-58 .

by inhibiting reabsorption • Physiological significance in adults is not understood 19-72 .25 Vit D3 to regulate blood Ca2+ levels • Stimulated by increased plasma Ca2+ • Inhibits activity of osteoclasts • Stimulates urinary excretion of Ca2+ & P043.Calcitonin • Secreted by C cells of thyroid gland • Works with PTH & 1.

28 11-59 .Parathyroid Glands • Are 4 glands embedded in lateral lobes of thyroid gland • Secrete Parathyroid hormone (PTH) – Most important hormone for control of blood Ca2+ levels Fig 11.

Parathyroid Hormone (PTH) • • • • • Secreted by parathyroid glands Is most important hormone in control of Ca2+ levels Release is stimulated by low blood Ca2+ levels Stimulates osteoclasts to reabsorb bone Stimulates kidneys to reabsorb Ca2+ from filtrate. & inhibits reabsorption of P043• Promotes formation of 1.25 Vit D3 that stimulates Ca2+ absorption by intestines • Many cancers secrete PTH-related protein that interacts with PTH receptors producing hypercalcemia 19-71 .

& intestines to increase blood Ca2+ levels Fig 11. kidney.Parathyroid Hormone • Release stimulated by decreased blood Ca2+ • Acts on bones.29 11-60 .

11 .Effects of Parathyroid Hormone Figure 16.


25 Vitamin D3 • Synthesis begins in skin when cholesterol derivative is converted to Vit D3 by sunlight Fig 19.21 19-75 .1.

25 Vitamin D3 continued • Directly stimulates intestinal absorption of Ca2+ & P043• When Ca2+ intake is inadequate.results in increased tendency of these to precipitate as hydroxyapatite • Stimulated by PTH • Inadequate Vit D in diet & body causes osteomalacia & rickets (loss of bone calcification) 19-76 .1. directly stimulates bone reabsorption • Stimulates kidney to reabsorb Ca2+ and P043 – Simultaneously raising Ca2+ & P043.

Overview of Hormonal Control of Fig 19.23 Fig 19.24 2+ Ca 19-77 .

Adrenal Gland 11-45 .

18 11-46 .Adrenal Glands • Sit on top of kidneys • Each consists of outer cortex & inner medulla – 2 arise differently during development Fig 11.

Adrenal Glands – Medulla synthesizes & secretes 80% Epi & 20% NE • Controlled by sympathetic – Cortex is controlled by ACTH & secretes: • Cortisol which inhibits glucose utilization & stimulates gluconeogenesis • Aldosterone which stimulate kidneys to reabsorb Na+ and secrete K+ • & some supplementary sex steroids 11-47 .

Adrenal Medulla • Hormonal effects of Epi last 10X longer than NE • Innervated by preganglionic Symp fibers • Activated during "fight or flight" response – Causes: • • • • Increased respiratory rate Increased HR & cardiac output General vasoconstriction which increases venous return Glycogenolysis & lipolysis 11-49 .

Effects of Epinephrine Secretion from Adrenal Medulla .

stimulating glycogenolysis & lipolysis Fig 19.15 19-57 .Metabolic Effects of Epi & Norepi • Are similar to glucagon.

decreases inflammatory response • Androgens: Zona reticularis – Weak androgens secreted then converted to testosterone by peripheral tissues. Stimulate pubic and axillary hair growth and sexual drive in females . Increases rate of sodium reabsorption by kidneys increasing sodium blood levels • Glucocorticoids: Zona fasciculata – Cortisol is major hormone. Increases fat and protein breakdown.Hormones of Adrenal Cortex • Mineralocorticoids: Zona glomerulosa – Aldosterone produced in greatest amounts. increases glucose synthesis.

Regulation of Cortisol Secretion .

and amino acids .Glucocorticoids (Cortisol) • Help the body resist stress by: – Keeping blood sugar levels relatively constant – Maintaining blood volume and preventing water shift into tissue • Cortisol provokes: – Gluconeogenesis (formation of glucose from noncarbohydrates) – Rises in blood glucose. fatty acids.

ketogenesis. & protein breakdown – Protein breakdown increases amino acid levels for use in gluconeogenesis in liver 19-58 . including fasting & exercise • Where it supports effects of glucagon • Promotes lipolysis.Metabolic Effects of Cortisol • Cortisol is secreted in response to ACTH – Which is often released in response to stress.

Metabolic Effects of Cortisol continued Fig 19.16 19-59 .

15 .Stress and the Adrenal Gland Figure 16.

20 11-50 .Stress & the Adrenal Gland • Stress induces a non-specific response called general adaptation syndrome (GAS) – Causes ACTH & cortisol release – Often affects physiology negatively Fig 11.

secrete somatostatin . secrete glucagon • Beta cells.Pancreas • Located along small intestine and stomach. secrete insulin • Delta cells. retroperitoneal • Exocrine gland – Produces pancreatic digestive juices • Endocrine gland – Consists of pancreatic islets – Composed of • Alpha cells.

Glucagon • A 29-amino-acid polypeptide hormone that is a potent hyperglycemic agent • Its major target is the liver. where it promotes: – Glycogenolysis – the breakdown of glycogen to glucose – Gluconeogenesis – synthesis of glucose from lactic acid and noncarbohydrates – Release of glucose to the blood from liver cells .

adipose tissue. releasing functional insulin • Insulin: – Lowers blood glucose levels – Enhances transport of glucose into body cells – Counters metabolic activity that would enhance blood glucose levels . and satiety center of hypothalamus • A 51-amino-acid protein consisting of two amino acid chains linked by disulfide bonds • Synthesized as part of proinsulin and then excised by enzymes.Insulin • Target tissue is the liver. muscle.

31 11-64 .Islets of Langerhans continued • Betas secrete insulin in response to low blood glucose – Promotes entry of glucose into cells – & conversion of glucose into glycogen & fat – Decreases blood glucose Fig 11.

7 19-40 .Insulin & Glucagon Secretion • Normal fasting glucose level is 65– 105 mg/dl – Insulin & glucagon normally prevent levels from rising above 170mg/dl after meals or falling below 50mg/dl between meals Fig 19.

17 .Regulation of Blood Glucose Levels • The hyperglycemic effects of glucagon and the hypoglycemic effects of insulin Figure 16.

Regulation of Insulin Secretion .

10 19-44 .Fig 19.

Effects of ANS on Insulin & Glucagon • ANS innervates islets • Activation of Parasymp NS stimulates insulin secretion • Activation of Symp NS stimulates glucagon & inhibits insulin – This can cause "stress hyperglycemia" 19-45 .

Diabetes Mellitus • Characterized by chronic high blood glucose levels (hyperglycemia) • Type I (insulin dependent or IDDM) is due to insufficient insulin secretion • Type II (insulin independent or NIDDM) is due to lack of effect of insulin 19-49 .

resulting in hypoglycemia .Diabetes Mellitus (DM) • Results from hyposecretion or hypoactivity of insulin • The three cardinal signs of DM are: – Polyuria – huge urine output – Polydipsia – excessive thirst – Polyphagia – excessive hunger and food consumption • Hyperinsulinism – excessive insulin secretion.

18 .Diabetes Mellitus (DM) Figure 16.


producing ketoacidosis • Increased glucagon levels stimulate glycogenolysis in liver 19-51 .Type I Diabetes  b cells of islets are destroyed by autoimmune attack • Glucose is unable to enter resting muscle or adipose cells – Rate of fat synthesis lags behind rate of lipolysis – Fatty acids are converted to ketone bodies.

12 19-52 .Effects of Uncontrolled Type I Diabetes Fig 19.

blurred vision. hunger.14 19-54 .Hypoglycemia • Reactive hypoglycemia is oversecretion of insulin due to an exaggerated response of b cells to a rise in glucose – Occurs in people who are genetically predisposed to type II diabetes – Symptoms include tremors. & confusion Fig 19. weakness.

Miscellaneous Glands & Hormones 11-65 .

32 11-66 .Pineal Gland • Is located in basal forebrain near thalamus • Secretes melatonin in response to activity of suprachiasmatic nucleus (SCN) of hypothalamus Fig 11.

Pineal Gland continued • SCN is primary timing center for circadian rhythms – Reset by daily light/dark changes • Melatonin is involved in aligning physiology with sleep/wake cycle & seasons – Secreted at night & is inhibited by light – Inhibits GnRH (antigonadotropic) in many animals 11-67 .

33 11-68 .Thymus • Is located around trachea below thyroid • Produces T cells of immune system & hormones that stimulate them Fig 11.

and somatomammotropin 11-69 . & progesterone • Placenta secretes estrogen. progesterone. hCG.Sex & Reproductive Hormones • Gonads (testes & ovaries) secrete steroid hormones testosterone. estrogen.

Estrogen • Causes epiphyseal discs (cartilaginous growth plates) to seal (ossify) which stops growth • Is necessary for proper bone mineralization & prevention of osteoporosis • Stimulates osteoblast activity & suppresses formation of osteoclasts 19-73 .

interleukins) • Growth factors (promote growth & cell division) • Neutrophins (provides trophic support for normal & regenerating neurons) 11-71 .Autocrine & Paracrine Regulation • Autocrine regulators are produced & act within same tissue of an organ – All autocrines control gene expression in target cells – Paracrine regulators are autocrines that are produced within one tissue & act on different tissue in same organ. – Autocrines & paracrines include: • Cytokines (lymphokines.


Table 11.2 .

6 .Table 11.

Table 11.7 .

Table 11.8 .