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Chapter 18The Endocrine System

• Endocrine and nervous systems work together

• Endocrine system– hormones released into the bloodstream travel

throughout the body– results may take hours, but last longer

• Nervous system– certain parts release hormones into blood– rest releases neurotransmitters excite or inhibit nerve,

muscle & gland cells– results in milliseconds, brief duration of effects

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General Functions of Hormones

• Help regulate:– extracellular fluid

– metabolism

– biological clock

– contraction of cardiac & smooth muscle

– glandular secretion

– some immune functions

• Growth & development• Reproduction

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Endocrine Glands Defined

• Exocrine glands– secrete products into ducts which empty into body

cavities or body surface– sweat, oil, mucous, & digestive glands

• Endocrine glands– secrete products (hormones) into bloodstream– pituitary, thyroid, parathyroid, adrenal, pineal– other organs secrete hormones as a 2nd function

• hypothalamus, thymus, pancreas,ovaries,testes, kidneys, stomach, liver, small intestine, skin, heart & placenta

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Hormone Receptors

• Hormones only affect target cells with specific membrane proteins called receptors

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Circulating & Local Hormones

• Circulating hormones– act on distant targets– travel in blood

• Local hormones– paracrines act on

neighboring cells– autocrines act on same

cell that secreted them

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Lipid-soluble Hormones• Steroids

– lipids derived from cholesterol on SER

– different functional groups attached to core of structure provide uniqueness

• Thyroid hormones– tyrosine ring plus attached

iodines are lipid-soluble

• Nitric oxide is gas

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Water-soluble Hormones• Amine, peptide and

protein hormones– modified amino acids or

amino acids put together– serotonin, melatonin,

histamine, epinephrine– some glycoproteins

• Eicosanoids– derived from arachidonic

acid (fatty acid)– prostaglandins or

leukotrienes

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Action of Lipid-Soluble Hormones

• Hormone diffuses through phospholipid bilayer & into cell

• Binds to receptor turning on/off specific genes

• New mRNA is formed & directs synthesis of new proteins

• New protein alters cell’s activity

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Action of Water-Soluble Hormones• Can not diffuse through plasma membrane

• Hormone receptors are integral membrane proteins – act as first messenger

• Receptor protein activates G-protein in membrane

• G-protein activates adenylate cyclase to convert ATP to cAMP in the cytosol

• Cyclic AMP is the 2nd messenger

• Activates kinases in the cytosol to speed up/slow down physiological responses

• Phosphodiesterase inactivates cAMP quickly

• Cell response is turned off unless new hormone molecules arrive

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Hormonal Interactions• Synergistic effect

– a second hormone, strengthens the effects of the first– two hormones acting together for greater effect– thyroid strengthens epinephrine’s effect upon lipolysis

• Permissive effect– you need two hormone present for one hormone to

work properly– estrogen & LH are both needed for oocyte production

• Antagonistic effects– two hormones with opposite effects– insulin promotes glycogen formation & glucagon

stimulates glycogen breakdown

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Control of Hormone Secretion

• Regulated by signals from nervous system, chemical changes in the blood or by other hormones

• Negative feedback control (most common)– decrease/increase in blood level is reversed

• Positive feedback control– the change produced by the hormone causes

more hormone to be released

• Disorders involve either hyposecretion or hypersecretion of a hormone

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Hypothalamus and Pituitary Gland

• Both are master endocrine glands since their hormones control other endocrine glands

• Hypothalamus is a section of brain above where pituitary gland is suspended from stalk

• Hypothalamus receives input from cortex, thalamus, limbic system & internal organs

• Hypothalamus controls pituitary gland with 9 different releasing & inhibiting hormones

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5 types of cells:• somatotrophs: secrete

hGH/somatotropin

• thyrotrophs: secrete TSH/thyrotropin

• gonadotrophs: secrete FSH, LH

• lactotrophs: secrete prolactin

• corticotrophs: secrete ACTH/corticotropin & MSH

Hormones:human growth hormone- hGHthyroid stimulating - TSHfollicle stimulating- FSHleutinizing hormone - LHprolactinadrenocorticotropin - ACTHmelanocyte stimulating - MSH

Pituitary Gland

• Pea-shaped, 1/2 inch gland found in sella turcica of sphenoid

• Infundibulum attaches it to brain

• Anterior lobe = 75% develops from roof of mouth

• Posterior lobe = 25%– ends of axons of 10,000 neurons found in

hypothalamus

– neuroglial cells called pituicytes

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Human Growth Hormone• Produced by somatotrophs• induces target cells to make insulin-like growth factors (IGFs) that

act locally or enter bloodstream– common target cells of IGFs are liver, skeletal muscle, cartilage and bone– GH + IGFs increase cell growth & cell division by increasing their uptake of

amino acids & synthesis of proteins– stimulate lipolysis in adipose so fatty acids used for ATP– retard use of glucose for ATP production by cells– reduces uptake of glucose by the liver and promote breakdown of liver

glycogen– so blood glucose levels stay high enough to supply brain

• Excess of growth hormone– raises blood glucose concentration

– pancreas releases insulin continually

– Leads to beta-cell burnout

• Diabetogenic effect– causes diabetes mellitis if no insulin activity can occur eventually

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Regulation of hGH• Low blood sugar stimulates

release of GNRH from hypothalamus– anterior pituitary releases

more hGH, more glycogen broken down into glucose by liver cells

• High blood sugar stimulates release of GHIH from hypothalamus– less hGH from anterior

pituitary, glycogen does not breakdown into glucose

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Thyroid Stimulating Hormone (TSH)

• Hypothalamus regulates thyrotroph cells

• Thyrotroph cells produce TSH

• TSH stimulates the synthesis & secretion of T3 and T4

• Metabolic rate stimulated

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Thyroid Gland

• comprised of microscopic sacs called follicles = follicular cells making up the walls, surrounds a lumen

• synthesize T3 & T4 (thyroxin)• In between follicular cells cells are

parafollicular cells– produce calcitonin

•On each side of trachea is lobe of thyroid•connected by an isthmus•Weighs 1 oz & has rich blood supply

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Formation of Thyroid Hormone

• Iodide trapping: follicular cells actively take up iodine from blood

• Synthesis of thyroglobulin (TGB): follicular cells make TGB - secreted into the follicle lumen as the material colloid

• Iodination of colloid: iodine ions are oxidated (I2- -> I2) by peroxidase within the cell– oxidized iodine then binds onto tyrosine residues

on the TGB within colloid

• Coupling of T1 and T2: forms T3 & T4• Uptake of colloid by follicular cells:

digestion cleaves off T3 and T4• Secretion of T3 & T4 into blood: T3 & T4

are transported in blood bound to thryoxine-binding globulin

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Actions of Thyroid Hormones

• T3 & T4 = increases metabolic rate

stimulates synthesis of protein

stimulates breakdown of fats

stimulates cholesterol excretion

increases use of glucose & oxygen

(ATP production)

increases body temperature (calorigenic effect)

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Control of T3 & T4 Secretion

• Low blood levels of hormones stimulate hypothalamus -> TRH

• It stimulates pituitary to release TSH

• TSH stimulates gland to raise blood levels

• T3 and T4 regulate themselves through a negative feedback loop

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Parathyroid Glands

• 4 pea-sized glands found on back of thyroid gland

• Principal cells produce parathyroid hormone (PTH)

• Oxyphil cell function is unknown

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Parathyroid Hormone• Raises blood calcium levels

– increases activity of osteoclasts (bone degrading cells)

– increases reabsorption of Ca+2 by kidney

– promote formation of calcitriol (vitamin D3) by kidney which increases absorption of Ca+2 and Mg+2 by intestinal tract

• Opposite function of calcitonin (thyroid)

• High or low blood levels of Ca+2 stimulate the release of different hormones --- PTH or CT– high level of calcium in blood - release of calcitonin by parafollicular cells,

promotes uptake of calcium into bone matrix, lowers blood calcium– low level of calcium in blood - release of PTH by parathyroid glands,

promotes release of calcium from bone, raises blood calcium

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Follicle Stimulating Hormone (FSH)

• Releasing hormone from hypothalamus controls gonadotrophs

• Gonadotrophs release follicle stimulating hormone

• FSH functions – initiates the formation of follicles within the ovary– stimulates follicle cells to secrete estrogen– stimulates sperm production in testes

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Luteinizing Hormone (LH)

• Releasing hormones from hypothalamus stimulate gonadotrophs

• Gonadotrophs produce LH

• In females, LH stimulates– secretion of estrogen– ovulation of 2nd oocyte from ovary– formation of corpus luteum– secretion of progesterone

• In males, stimulates interstitial cells to secrete testosterone

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Ovaries and Testes

• Ovaries– estrogen, progesterone, relaxin & inhibin– regulate reproductive cycle, maintain pregnancy &

prepare mammary glands for lactation

• Testes– produce testosterone– regulate sperm production & 2nd sexual

characteristics

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Prolactin (PRL)

• Hypothalamus regulates lactotroph cells

• Lactotrophs produce prolactin

• Under right conditions, prolactin causes milk production

• Suckling reduces levels of hypothalamic inhibition and prolactin levels rise along with milk production

• Nursing ceases & milk production slows

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Melanocyte-Stimulating Hormone

• Secreted by corticotroph cells

• Releasing hormone from hypothalamus increases its release from the anterior pituitary

• Function not certain in humans (increase skin pigmentation)

• May have a role in promoting sexual performance

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Adrenocorticotrophic Hormone

• Hypothalamus releasing hormones stimulate corticotrophs

• Corticotrophs secrete ACTH (& MSH also)

• ACTH stimulates cells of the adrenal cortex

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Adrenal Glands

• One on top of each kidney• 3 x 3 x 1 cm in size and weighs 5 grams• Cortex produces 3 different types of

hormones from 3 zones of cortex: mineralcorticoids (aldosterone), glucocorticoids (cortisol) & androgens

• Medulla produces epinephrine & norepinephrine

• Cortex derived from mesoderm

• Medulla derived from ectoderm

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AdrenalGland

• Cortex– 3 zones

• Medulla

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Mineralocorticoids

• 95% of these hormones - aldosterone

• Functions– increase reabsorption of Na+ with Cl- , bicarbonate and water following it

– promotes excretion of K+ and H+

• dehydration, hemorrhage (decrease in blood volume) - decreases blood pressure - secretion of renin from kidneys which stimulates angiotensin II release from lungs - stimulates aldosterone release from adrenal cortex - increases water uptake from kidneys and increased excretion of K+ into urine

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Glucocorticoids• 95% of hormonal activity is due to cortisol

• neurosecretory cells secrete corticotropin-releasing hormone (CRH)

• CRH promotes the release of ACTH where it stimulates the adrenal cortex to secrete corticol

• Functions = helps regulate metabolism – increases rate of protein synthesis – increases conversion of amino acids to

glucose – energy for protein synthesis– stimulates lipolysis for glucose synthesis

(for energy)– increases glucose synthesis – ATP

production provides resistance to stress by making nutrients available for ATP

– raises BP by vasoconstriction (decreases blood loss)

– anti-inflammatory effects reduced (skin cream)

• reduces release of histamine from mast cells• decreases capillary permeability• depresses phagocytosis

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Androgens

• Small amount of male hormone produced by the zona reticularis– insignificant in males– may contribute to sex drive in females– is converted to estrogen in postmenopausal

females

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Adrenal Medulla• hormone producing cells = Chromaffin cells

receive direct innervation from sympathetic nervous system

• Produce epinephrine & norepinephrine• Hormones are sympathomimetic

– effects mimic those produced by sympathetic NS– cause fight-flight behavior

• sympathetic preganglionic neurons secrete acetylcholine - which stimulates secretion by the AM

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Posterior Pituitary Gland (Neurohypophysis)

• Does not synthesize hormones

• Consists of axon terminals of hypothalamic neurons

• Neurons release two neurotransmitters that enter capillaries– antidiuretic hormone– oxytocin

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Oxytocin• Two target tissues both involved in neuroendocrine

reflexes

• During delivery– baby’s head stretches cervix

– hormone release enhances uterine muscle contraction

– baby & placenta are delivered

• After delivery– suckling & hearing baby’s cry stimulates milk ejection

– hormone causes muscle contraction & milk ejection

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Antidiuretic Hormone (ADH)• Known as vasopressin

• Functions– decrease urine production– decrease sweating– increase BP

• Dehydration– ADH released

• Overhydration– ADH inhibited

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Pancreas

• Organ (5 inches) consists of head, body & tail• Cells (99%) in acini produce digestive enzymes• Endocrine cells in pancreatic islets produce hormones• Exocrine acinar cells surround a small duct = digestive

enzymes

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• Endocrine cells secrete near a capillary

• 1 to 2 million pancreatic islets

• Contains 4 types of endocrine cells

• Alpha cells (20%) produce glucagon• Beta cells (70%) produce insulin• Delta cells (5%) produce somatostatin• F cells produce pancreatic polypeptide

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Regulation of Glucagon & Insulin Secretion

• Low blood glucose stimulates release of glucagon

• High blood glucose stimulates secretion of insulin

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Pineal Gland• Small gland attached to 3rd ventricle of

brain

• Consists of pinealocytes & neuroglia

• Melatonin responsible for setting of biological clock

• Jet lag & SAD treatment is bright light

• Melatonin secretion produces sleepiness - occurs during darkness due to lack of stimulation from sympathetic ganglion

•light strikes retina and stimulatessuprachiasmatic region ofhypothalamusstimulates sympathetic ganglionwhich then stimulates thepineal glandlight -> NE -> no melatonindark -> lack of NE -> melatonin

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Thymus Gland

• Important role in maturation of T cells

• Hormones produced by gland promote the proliferation & maturation of T cells– thymosin– thymic humoral factor– thymic factor– thymopoietin

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Eicosanoids• Local hormones released by all body cells normally and upon

trauma• synthesized from arachidonic acid (fatty acid)• Leukotrienes influence WBCs – inflammation & allergic

response• Prostaglandins alter

– smooth muscle contraction, glandular secretion, blood flow, platelet function, nerve transmission, metabolism etc.

– Ibuprofen & other nonsteroidal anti-inflammatory drugs treat pain, fever & inflammation by inhibiting prostaglandin synthesis

– PGs are synthesized by an enzyme complex containing the enzymes COX1 and COX2

– Aspirin and ibuprofen can inhibit activity of COX1 isoform – short term anti-inflammatory

– Vioxx, Bextra and Celebrex inhibit activity of COX2 isoform – long term anti-inflammatory

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Pituitary Gland Disorders

• Hyposecretion during childhood = pituitary dwarfism (proportional, childlike body)

• Hypersecretion during childhood = giantism– very tall, normal proportions

• Hypersecretion as adult = acromegaly– growth of hands, feet, facial features & thickening of skin

Thyroid Gland Disorders• Hyposecretion of TSH during infancy results in dwarfism & retardation called

cretinism

• Hypothyroidism - undersecretion of T3 and T4– Caused by low production of TSH

– in adults produces sensitivity to cold, low body temp. weight gain & mental dullness

• Hyperthyroidism – oversecretion of T3 and T4 (Grave’s disease)– caused by the inability of the thyroid to respond to TSH levels

– weight loss, cardiac complications, increased fluid behind the eyes & goiter = enlarged thyroid

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Cushing’s Syndrome• Hypersecretion of glucocorticoids• Redistribution of fat, spindly arms & legs due to muscle loss• Wound healing is poor, bruise easily

Addison’s disease• Hyposecretion of glucocorticoids

– hypoglycemia, muscle weakness, low BP, dehydration due to decreased Na+ in blood

– mimics skin darkening effects of MSH

– potential cardiac arrest

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Diabetes Mellitus & Hyperinsulinism

• Diabetes mellitus marked by hyperglycemia– excessive urine production (polyuria)– excessive thirst (polydipsia)– excessive eating (polyphagia)

• Type I----deficiency of insulin (under 20)

• Type II---adult onset– drug stimulates secretion of insulin by beta cells– cells may be less sensitive to hormone