Necessary for integration of cell activities Mechanisms

gap junctions pores in cell membrane allow signaling chemicals to move from

cell to cell neurotransmitters

released from neurons to travel across gap to 2nd cell paracrine (local) hormones

secreted into tissue fluids to affect nearby cells hormones (strict definition)

chemical messengers that travel in the bloodstream

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Second messengers

Second messengers

Hormone chemical messenger secreted into

bloodstream, stimulates response in another tissue or organ

Target cells have receptors

for hormone

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Endocrine glands produce hormones

Endocrine system endocrine organs hormone producing cells

in other organs

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Major organs of endocrine system

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

Endocrine glands no ducts, release hormones into tissue fluids, have dense

capillary networks to distribute hormones intracellular effects, alter target cell metabolism

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Name one organ that has both exocrine and

endocrine functions!

Communication nervous - both electrical and chemical endocrine - only chemical

Speed and persistence of response nervous - reacts quickly (1 - 10 msec), stops quickly endocrine - reacts slowly (hormone release in seconds

or days), effect may continue for weeks Adaptation to long-term stimuli

nervous - response declines (adapts quickly) endocrine - response persists

Area of effect nervous - targeted and specific (one organ) endocrine - general, widespread effects (many organs)

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Many functions of the hypothalamus are carried out by pituitary gland

Shaped like a flattened funnel, forms floor and walls of third ventricle

Regulates primitive functions from water balance to sex drive

Hypothalamus

Pituitary

Pineal

Suspended from hypothalamus by stalk (infundibulum) Location and size

housed in sella turcica of sphenoid bone 1.3 cm diameter

Adenohypophysis (anterior pituitary) arises from hypophyseal pouch (outgrowth of pharynx)

Neurohypophysis (posterior pituitary) arises from brain

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17-17

Is the neurohypophysis the anterior pituitary?

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Hypothalamic hormones travel in portal system from hypothalamus to anterior pituitary for secretion

This is different from the hepatic portal system

‘releasing hormone’

“releasing hormone”

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Hypothalamus notices cold weather and makes TRH TRH travels to the anterior lobe by the

hypothalamohypophyseal portal system Anterior lobe secretes

TSH which goes to the thyroid gland via blood

More thyroid hormone in cold weather = more body heat

Tropic hormones target other endocrine glands gonadotropins target gonads

FSH (follicle stimulating hormone) stimulates production of egg or sperm cells

LH (luteinizing hormone) females - stimulates ovulation and corpus luteum to

secrete progesterone and estrogen males - stimulates interstitial cells of testes to secrete

testosterone TSH (thyroid stimulating hormone)

stimulates growth of gland and secretion of TH

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ACTH or corticotropin regulates response to stress, stimulates adrenal cortex

corticosteroids regulate glucose, fat and protein metabolism Prolactin

female - milk synthesis after delivery male - LH sensitivity, thus testosterone secretion

GH = growth hormone or somatotropin

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Childhood and adolescence bone, cartilage and muscle growth Stimulates growth at epiphyseal plates

Adulthood increase osteoblastic activity and appositional growth

affecting bone thickening and remodeling blood concentration decrease by age 75 to ¼ of that of

adolescent Levels of GH (fluctuates throughout day)

higher during deep sleep, after high protein meals, after vigorous exercise

lower after high carbohydrate/sugar meals17-22

Principle hormones and target organs shown

Axis - refers to way endocrine glands interact

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prolactin

The hormones of the posterior pituitary are produced in the hypothalamus and transported to the posterior lobe for storage and release

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ADH targets kidneys

water retention, reduce urine also functions as neurotransmitter

Oxytocin labor contractions, lactation possible role in

sperm transport emotional bonding

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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LAB

Negative feedback target organ hormone

levels inhibits release of tropic hormones

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Positive feedback stretching of uterus OT

release, causes more stretching of uterus, until delivery

Peak secretion ages 1-5; by puberty 75% lower Produces serotonin by day, converts it to melatonin at

night May regulate timing of puberty in humans Melatonin in SAD (seasonal affective disorder) and

PMS (premenstrual syndrome) depression, sleepiness, irritability and carbohydrate craving by phototherapy

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Location: mediastinum, superior to heart

Involution after puberty Secretes hormones that regulate

development and later activation of T-lymphocytes thymopoietin and thymosins

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Largest endocrine gland; high rate of blood flow arises root of

embryonic tongue

Anterior and lateral sides of trachea two large lobes

connected by isthmus

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Don’t confuse thyroid with thymus

Thyroid hormone body’s metabolic rate and O2 consumption calorigenic effect - heat production heart rate and contraction strength respiratory rate stimulates appetite and breakdown CHO, lipids and

proteins C (calcitonin or parafollicular) cells

produce calcitonin that blood Ca2+ , promotes Ca2+

deposition and bone formation especially in children

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Regulate calcium levels Parathyroid hormone

(PTH) release blood Ca2+ levels promotes synthesis of

calcitriol absorption of Ca2+

urinary excretion bone resorption

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LAB

Sympathetic ganglion innervated by sympathetic preganglionic fibers consists of modified neurons called chromaffin cells stimulation causes release of catecholamines

(epinephrine, norepinephrine (NE)) Hormonal effect is longer lasting

Increases alertness, anxiety, or fear increases blood pressure, heart rate and air flow raises metabolic rate

inhibits insulin secretion stimulates gluconeogenesis and glycogenolysis

Stress causes medullary cells to stimulate cortex

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Corticosteroids mineralocorticoids (zona glomerulosa)

control electrolyte balance, aldosterone promotes Na+ retention and K+ excretion

glucocorticoids (zona fasciculata) especially cortisol, stimulates fat and protein catabolism,

gluconeogenesis (from a.a.’s and FA’s) and release of fatty acids and glucose into blood

anti-inflammatory effect becomes immune suppression with long-term use

Sex steroids (zona reticularis) androgen (including DHEA which other tissues convert to

testosterone) and estrogen (important after menopause)

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Retroperitoneal, inferior and dorsal to stomach

17-37

cells glucagon cells insulin cells somatostatin

C

Islets of Langerhans

ExocrineEndocrine

1-2 million islets produce hormones 98% of organ produces digestive enzymes (exocrine)

Insulin (from cells) secreted in absorptive state, when blood glucose ↑ stimulates glucose and amino acid uptake stimulates glycogen, fat and protein synthesis antagonizes glucagon

17-39

Glucagon (from cells) secreted when blood glucose goes ↓ stimulates glycogenolysis, fat catabolism (release of FFA’s)

Somatostatin (from delta () cells) is also made by the hypothalamus! secreted with ↑blood glucose and amino acids after a meal paracrine action = inhibits secretion of insulin, glucagon by

and cells

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Why? It’s not clear yet!

Estrogens and androgens are both steroids Ovary – female

an estrogen called ‘estradiol’ before ovulation then progesterone after ovulation

Testes – male testosterone

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More when we get to the

reproduction section

Skin - helps produce D3 Liver 15% of erythropoietin (stimulates bone marrow) Kidneys

produces 85% of erythropoietin

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Steroids derived from cholesterol sex steroids, corticosteroids

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Only differ in their functional groups

C

Steroids derived from cholesterol sex steroids, corticosteroids

Monoamines (biogenic amines) derived from amino acids

thyroid hormones and catecholamines (norepinephrine, epinephrine, dopamine)

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Most are made from

tyrosine

C

Steroids derived from cholesterol sex steroids, corticosteroids

Monoamines (biogenic amines) derived from amino acids

thyroid hormones and catecholamines (norepinephrine, epinephrine, dopamine)

Peptides and glycoproteins Oxytocin, ADH, insulin all releasing and inhibiting

hormones of hypothalamus most of anterior pituitary

hormones

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C

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Both from the posterior pituitary

C

Monoamines and peptides are hydrophilic mix easily with blood plasma

Steroids and thyroid hormone are hydrophobic must bind to transport proteins for transport bound hormone - attached to transport protein,

prolongs half-life to weeks protects from enzymes and kidney filtration

unbound hormone leaves capillary to reach target cell (half-life a few minutes)

Transport proteins in blood plasma albumin, thyretin and TGB (thyroxine binding globulin)

bind to thyroid hormone steroid hormones bind to globulins (transcortin) aldosterone - no transport protein, 20 min. half-life

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Located on plasma membrane, the membranes of mitochondria, other organelles, or the nucleus

Usually thousands for given hormone hormone binding turns metabolic pathways on or off

Exhibit specificity and saturation

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Complete Androgen Insensitivity Syndrome

= CAIS

Hydrophobic hormones penetrate plasma

membrane and enter nucleus

Hydrophilic hormones must bind to cell-

surface receptors

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TH binds to receptors on mitochondria

rate of aerobic respiration

ribosomes and chromatin Na+-K+ ATPase generates heat

second messenger

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1) Hormone binding activates G protein

2) Activates adenylate cyclase3) Produces cAMP4) Activates protein kinases5) Activates enzymes6) Metabolic reactions:

synthesis secretion change membrane potentials

Hormones may use different second messengers in different tissues.

Variations in hormone concentration and target cell sensitivity have noticeable effects on the body

Hyposecretion – inadequate hormone release tumor, lesion or disease destroys gland

head trauma affects pituitary gland’s ability to secrete ADH diabetes insipidus = chronic polyuria

Hypersecretion – excessive hormone release tumors or autoimmune disorder

toxic goiter (graves disease) – antibodies mimic effect of TSH on the thyroid

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Signs and symptoms of a deficiency of insulin action polyuria, polydipsia, polyphagia hyperglycemia, glycosuria, ketonuria osmotic diuresis

blood glucose levels rise above transport maximum of kidney tubules, glucose remains in urine (ketones also present)

increased osmolarity draws water into urine

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When insulin activates the insulin receptor, it moves the GLUcose Transporters (GLUTs) which allow glucose (blood sugar) into your cells to the cell membrane. This allows your cells to take up glucose and drops circulating blood sugar.

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TWO ways this system can be damaged1- Not enough insulin2- Insulin resistance

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Type I - 10% of cases ‘juvenile onset’ diabetes autoimmune destruction of cells diagnosed about age 12 treated with diet, exercise, monitoring of blood glucose

and regular injections of insulin Type I.5 - 15% of cases

once grouped with Type II because it occurs in adults no insulin resistance autoimmune destruction of cells diagnosed in adults treated with diet, exercise, monitoring of blood glucose may require periodic injections of insulin

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Type II - 75% 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

May cure the condition men with waists > 40 inches are at increased risk women > 35 inches are at increased risk

oral medications improve insulin secretion (sulfonylureas) or target cell sensitivity (thiazolidinedione like Avandia)

Treatment may require insulin

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Fat secretes a group of hormones called adipokines that may possibly impair glucose tolerance.

Visceral fat (almost all of it inside the abdomen) is more hormonally active than subcutaneous fat.

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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+ and K+

ketoacidosis occurs as ketones blood pH if continued causes dyspnea and eventually diabetic coma

Presentation of diabetic ketoacidosis To the untrained eye, patients appear drunk Sluggish, agitated, irritated, confused Breath may smell like nail polish remover Hyperventilation, shallow at first

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Fatal when not

treated quickly

25% of pediatric

diabetes patients are

diagnosed in DKA

Diabetic nephropathy #1 cause of kidney disease needing dialysis Usually causes death within 3 years

Diabetic neuropathy #1 cause of foot/leg amputations

Doubles the risk of heart attack death ↑↑ LDL cholesterol

Diabetic retinopathy #1 cause of blindness in the elderly

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Cushing syndrome - excess cortical secretion hyperglycemia, hypertension, weakness, edema muscle and bone loss occurs with protein catabolism buffalo hump and moon face = fat

deposition between shoulders or in face Addison’s Disease – cortical insufficiency

Autoimmune cause usually Insufficient aldosterone, insufficient cortisol Muscle weakness, lethargy, ↑ skin pigment, fainting may present with sudden pain of back, abdomen or legs low blood pressure

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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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Goiter

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, Thyroid Hormone, exophthalmos

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Cretinism

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Fig. 17.18

1- Iodide is absorbed from the blood2- Thyroglobulin is made in the cell and secreted into the follicle lumen3- Iodine gets added to make thyroglobulin4- TSH stimulates the follicle cell to take up the thyroglobulin and hydrolyse it to make T3 and T45- The follicle cell releases T3 and T4 into the blood.

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Hormone signals must be turned off Taken up and degraded by liver and kidney Excreted in bile or urine Metabolic clearance rate (MCR) Half-life is the time required to clear 50% of

hormone

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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

17-70

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

Examples and their functions histamine

from mast cells in connective tissue causes relaxation of blood vessel smooth muscle

nitric oxide from endothelium of blood vessels, causes vasodilation

somatostatin from gamma cells, inhibits secretion of alpha and beta cells

catecholamines diffuse from adrenal medulla to cortex

17-71

Leukotrienes converted from arachidonic acid (by lipoxygenase) mediates allergic and inflammatory reactions

Prostacyclin (by cyclooxygenase) inhibits blood clotting and vasoconstriction

Thromboxanes (by cyclooxygenase) produced by blood platelets after injury; override prostacyclin,

stimulates vasoconstriction and clotting Prostaglandins (by cyclooxygenase): diverse; includes

PGE: relaxes smooth muscle in bladder, intestines, bronchioles, uterus and stimulates contraction of blood vessels

PGF: opposite effects

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Hypersecretion of growth hormones acromegaly thickening of the bones and soft tissues problems in childhood or adolescence

gigantism if oversecretion dwarfism if hyposecretion

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Hypoparathyroid surgical excision during thyroid surgery fatal tetany 3-4 days

Hyperparathyroid = excess PTH secretion tumor in gland causes soft, fragile and deformed bones blood Ca2+

renal calculi

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