Hormone

1
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

2
Endocrine Organs

• Major organs of endocrine system

3
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)

4
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

5
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

6
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

7
Pituitary Gland (Hypophysis)

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

8
Embryonic Development of Pituitary
9
Pituitary Gland Anatomy and Hormones of the
Neurohypophysis
10
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 (red box)secreted by anterior pituitary
  (under control of hypothalamic releasers and
  inhibitors)

11
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)
• ACTH (adrenocorticotropic hormone)
• PRL (prolactin)
• GH (growth hormone )

12
Anterior Pituitary Hormones

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

13
Pituitary Hormones - Pars Intermedia

• Adult human these cells fuse with anterior lobe
• Produce POMC (pro-opiomelanocortin) which is
  processed into ACTH and endorphins

14
Pituitary Hormones - Posterior Lobe

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

15
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

16
Hormone Actions 2

• 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

17
Growth Hormone

• 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, Ca2 absorption

18
Growth Hormone 2

• 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

19
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

20
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

21
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

22
Pituitary Disorders

• Hyperpituitarism
• childhood
• gigantism
• adult
• acromegaly - thickening of bones, soft tissues of
  hands, feet and face

23
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

24
Thymus

• Location mediastinum, superior to heart
• Involution after puberty
• Secretes hormones that regulate development and
  later activation of T-lymphocytes

25
Thyroid Gland Anatomy

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

26
Thyroid Gland

• Thyroid follicles
• filled with colloid and lined with simple
  cuboidal epith. (follicular cells) that secretes
  2 hormones, T3T4
• Thyroid hormone
• ? bodys metabolic rate and O2 consumption
• calorigenic effect - ? heat production
• ? heart rate and contraction strength
• ? respiratory rate
• Parafollicular cells
• produce calcitonin that ? blood Ca2, promotes
  Ca2 deposition and bone formation especially in
  children

27
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

28
Parathyroid Glands

• PTH
• ? blood Ca2
• ? absorption
• ? urinary excretion
• bone resorption
• Hypoparathyroid
• surgical excision
• fatal tetany 3-4 days
• Hyperparathyroid
• tumor causes soft, fragile and deformed bones, ?
  blood Ca2, renal calculi

29
Adrenal Gland
30
Adrenal Medulla

• Sympathetic ganglion innervated by sympathetic
  preganglionic fibers
• stimulation causes release of (nor-)epinephrine

31
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 FAs)
  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 estrogen (important after
  menopause)

32
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

33
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

34
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

35
Pancreas

• Retroperitoneal, inferior and dorsal to stomach

36
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

37
Pancreatic Hormones 2

• Glucagon (from ? cells)
• secreted in very low carbohydrate and high
  protein diet or fasting
• stimulates glycogenolysis, fat catabolism
  (release of FFAs) 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

38
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

39
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

40
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
• 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

41
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

42
Histology of Ovary
43
Ovary

• Granulosa cells 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
• Functions
• development of female reproductive system and
  physique
• regulate menstrual cycle, sustain pregnancy
• prepare mammary glands for lactation
• Both secrete inhibin suppresses FSH secretion

44
Histology of Testis
45
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

46
Endocrine Functions of Other Organs

• Heart - atrial natriuretic factor
• ? blood volume ? BP, from ? Na and H2O loss by
  kidneys
• Kidneys
• calcitriol - Ca2 and phosphate ? absorption, ?
  loss for bone deposition
• erythropoietin - stimulates bone marrow to
  produce RBCs
• Stomach and small intestines - enteric hormones
• coordinate digestive motility and secretion

47
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 estrogen, progesterone and others
• regulate pregnancy, stimulate development of
  fetus and mammary glands

48
Hormone Chemistry

• Steroids
• derived from cholesterol
• sex steroids, corticosteroids

• Monoamines (biogenic amines)
• derived from tyrosine
• catecholamines (norepinephrine, epinephrine,
  dopamine) and thyroid hormones

49
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)

50
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

51
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

52
Steroid Hormones

• Synthesized from cholesterol

53
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

54
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

55
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

56
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

57
Hormone Action, Other 2nd 3rd Messengers
58
Monoamines

• Synthesized from tyrosine, mostly hydrophilic,
  activate second messenger systems
• TH only one made from 2 tyrosine molecules

59
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

60
Thyroid Hormone Synthesis
61
Thyroid Hormone Action

• TH binds to receptors on mitochondria (?metabolic
  rate), ribosomes and chromatin (? protein
  synthesis)
• One protein produced Na-K ATPase generates
  heat

62
Enzyme Amplification
63
Regulation of Cell Sensitivity to a Hormone
64
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

65
Stress and Adaptation

• Any situation that upsets homeostasis and
  threatens ones 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

66
Alarm Reaction

• Initial response
• ? epinephrine and norepinephrine levels
• ? HR and ? BP
• ? blood glucose levels
• Sodium and water retention (aldosterone)

67
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

68
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

69
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

70
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
• PGEs relaxes smooth muscle in bladder,
  intestines, bronchioles, uterus and stimulates
  contraction of blood vessels
• PGFs opposite effects

71
Eicosanoid Synthesis