Opticchasm

infudibulum

Arterial bloodsupply

Hypothalamo-pituitaryportal vessels

Anteriorpituitary

Endocrinecells

To venouscirculation

Short portalvessels

Arterial bloodsupply

To venouscirculation

Posteriorpituitary

Medianeminence

Primarycapillaries

Axon toprimarycapillaries

Superiorhypophysealartery

Portalvenules

Secondarycapillaries

Anteriorpituitary

Posteriorpituitary

Pituitarystalk

Medianeminence

Transduction Pathways of Releasing Hormones

Hormone

Pathway

Location of action PKAa PIb

CRH

TRH

GnRH

AVP

Corticotrope of anteriorpituitary (ACTH)

Thyrotrope of anteriorpituitary (TSH)

Gonadotrope of anteriorpituitary (LH & FSH)

Corticotrope of anteriorpituitary; assists CRH inreleasing ACTH

+

+

+c

Transduction Pathways of Releasing Hormones (cont.)

GHRH

Somatostatin

PRL

Hormone

Pathway

Location of action PKAa PIb

Somatomammotropeof anterior pituitary (GH)

+ (?)

Release inhibitor

Somatomammotropeof anterior pituitary(inhibits GH release)

+d

aPKA, protein kinase AbPI, phosphatidylinositol pathwaycThe increase of cytoplasmic calcium concentrationmay be important in the actions of PI stimulationdInhibitory pathway of PKA

Effects of hypophysectomy

1. Cessation of growth & the retention of juvenile features.

2. Atrophy of adrenal cortes (zona fasciculata).

3. Atrophy of thyroid.

4. Decreased gonadal function in the adult.

5. Alterations in the metabolism of lipids, proteins, and carbohydrates.

6. Blanching of pigment cells in the skin of the lower vertebrates (fishes, amphibians, & reptiles

Growth Hormone (GH)Somatotropin

I. ChemistryStraight chain polypeptide of 191 AA (Two S-S

bonds)

Mole Weight: 22,000 deltons

Produced by somatotroph (acidophil) cells

Plasma Concentration 3-10 ng/ml

Circulating half-life: 20-30 minutes

Broken down by the liver

II. Biologic ActionsA. Supports Osteogenesis

(Epiphyseal-diaphyseal plate)

Stimulates release of peptide somatomedin from the liver1. Oversecretion (acidophilic adenoma)

(a) Giantism

(b) Acromegaly

2. Undersecretion

(a) Pituitary dwarf

(b) Simmond’s disease (hypophyseal cachexia)

Amino Acid Sequence of HGH

Epiphyseal-Diaphyseal Plate

Facial changes in a patient with acromegaly.Panel at left shows appearance of normal youngwoman. Middle & right show effects of acromegalywith coarsening of facial features.

Hand of someone with acromegaly (left)placed next to normal hand (right).

Somatotropin (cont.)

B. Promotes protein synthesis (anabolic effect)

Retards AA catabolism: transport into cell.

AA retention causes positive nitrogen - phosphate balance. Na+ + K+ excretion

C. Diabetogenic effect (Houssay animal)

Blocks hexokinase

Somatotropin (cont.)

Affects carbohydrate metabolism by:1. hyperglycemia

2. Inhibiting insulin action

3. muscle glycogen

4. Production of permanent diabetes mellitus (destroys B cells)

Somatotropin (cont.)

D. Peripheral mobilization of fats

(Pharmacologic doses)

[serum fatty acids]

E. Increase intestinal absorption of calcium

F. Increase renal tubular reabsorption of phosphorus

Somatotropin (cont.)

III. Regulation of releaseA. Stimulation (via Somatotropin Releasing

Hormone) SRH

Deficiency of energy substrate:1. Hypoglycemia

2. Exercise

3. Fasting

4. Plasma protein

5. Sleep

Somatotropin (cont.)

B. Inhibition (via somatostatin) IH1. Serum glucose

2. Cortisol

3. REM sleep

Somatotropin (cont.)

IV. Potential Clinical Use for Hypothalmic HormonesA. Somatotropin Releasing Hormone

Treats GH deficiency effects-short stature

B. Somatostatin (14 AA peptide)

Treatment of acromegaly

Growth Curve

% of totalgrowth

Age (years)

04 8 12 16 20

20

40

60

80

100

Age (years)

0 4 8 122 6 10 14Adult

0.4

0.5

0.6

0.7

0.8

0.9

1.0

1.1

1.2S

omat

omed

in L

evel

(U

/mL

)

(8) (6) (6) (4) (5) (5) (2)

•

•

•

• • • • •

Age

Wt.

P Growth H. + thyroxine

P Growth H.

P throxine

control

Prolactin

Chemistry

Unbranched polypeptide of 198 AA (human). It has 3disulfide bridges and a mole wt. of ~ 25,000. Secreted byacidphil cells (lactotrophs) of the adenohypophysis. The“prolactins” have a myriad of effects among vertebratesand hence a myriad of different names (lactogenic hormone;mammotrophin; galactin; luteotrophin; etc.) The “N&C”terminals are similar to those in growth hormone.

Half-life of 15-25 minutesSerum level 8 ng/mL female : 5 ng/mL male

Prolactin (cont.)

Biologic ActionsA. Non-Humans

1. Luteotropic effect (rats)- maintenance of the functional activity of the corpus luteum & release of progesterone (controlled by LH in humans.)

2.Maternal behavior (rabbits)- injections of prolactin into non-pregnant rabbits results in nest building.

Ovine (sheep) prolactin. The black bars indicate disulfide bridges.

Prolactin (cont.)

B. Human Functions

1. Mammotrophic effect- stimulates the mammary epithelium to secrete milk (i.e. produce milk.)

2. Affects function of adrenals, gonads, steroid synthesis, and lipolysis.

Prolactin (cont.)

Regulation of Release

A. Secretion (PRH- Prolactin Releasing Hormone)1. Pregnancy- reaches peak during parturition

2. Stimulation of nipples (nursing baby)

3. Surgical or psychologic stress

4. Coitus

Prolactin (cont.)

B. Inhibition (PIH- Dopamine)

1. Dopmine is a product of L-Dopa (used to treat Parkinson’s disease- neurological disorder- tremors)

2. Estrogen & progesterone- high levels during pregnancy inhibit action of prolactin. After birth, milk production increases.

PhysiologicalPhysiological PathologicalPathological PharmacologicalPharmacological

Causes of Increased ConcentrationCauses of Increased Concentrationof Production in Serumof Production in Serum

Sleep

SuckingExercise

Hypothalmic disorders,

Chiari-Frommel syndrome

Renal failureSexual intercourse

Pregnancy Pituitary tumors Various drugs (e.g., chlorpromazine)

EstrogensThyrotropin-releasing hormone

Insulin-induced hypoglycemiaHypothyroidismArginineParathormone

Nelson’s syndromeAdrenal insufficiencyEctopic production by tumors

Stress (e.g., surgery)

Pituitary stalk sections

Oral contraceptives

e.g., sarcoid infiltration

CorticotropinAdrenocorticotrophic Hormone (ACTH)

Chemistry

Straight chain polypeptide of 39 AA & a mole weight of 4,500.It is secreted by corticotroph cells (basophil). ACTH has a 13AA sequence from its N-terminal which is identical with MSH.It therefore has a natural tendency to melanosize cells likeB-lipotrophin (AA 41-58)

Biologic Actions

1. ACTH controls the release of glucocorticoids (cortisol and corticosterone) from the zona fasciculata of the adrenal cortex.

2. Release of adrenal androgens

Zona Glomerulosa

ZonaFasciculata

Medulla

Zona Reticularis

Regulation of Release

Almost any type of physical or mental stress

causes the release of CRH from the hypoth-

alamus. This causes the release of ACTH

which glucocorticods.

Regulation of Release (cont.)

BIOASSAYS

1. Depletion of ascorbic acid (vitamin C).

a) formation of collagen

b) [iron] in body fluids

c) Scurvy (20-30 week deficiency)

Failure of wounds to heal ( collagen)

Cessation of bone growth

Fragile walls of blood vessels

(cont.)

2. Depletion of cholesterol.

3. Incubation methods:

Incubate adrenal slices with ACTH.

Measure cortisones produced.

4. Maintenance of adrenal weight in

animals.

Thyrotropin

I. CHEMISTRY:

TSH, FSH, & LH are glycoproteins produced by basophil cells and having

chemically dissimilar subunits non-covalently linked together.

Thyrotropin (cont.)

Subunits:

a) Alpha - this subunit is identical in the

identical in the three hormones.

b) Beta - provides hormonal specificity.

Produced by thyrotroph (basophil) cells

Mole wt. 26,000

Circulating half-life is 60 minutes

Broken down by kidney

Thyrotropin (cont.)

II. BIOLOGIC ACTIONS

1. Maintenance of the structural and

functional integreties of the thyroid

gland.

2. Controls iodine uptake (iodide pump)

3. Maintains normal secretory epithelium-

low columnar.

Thyrotropin (cont.)

4. Causes production and release of

thyroxine.

Thyroid Follicles

NormalHyperactive

(hyperthyroidism)

Hypoactive

colloiddepletedcolloidsecretory

epithelium

Thyrotropin (cont.)

III. Regulation of releaseA. Stimulation (via thyrotropin releasing

hormone)

Negative feedback1) thyroxine

2) body temperature

B. Inhibition1) serum thyroxine

2) body temperature

Thyrotropin (cont.)

IV. Assay MethodsA. Bioassay

1) height of secretory epithelium

2) Number of colloid droplets in cells

3) Iodine depletion in 1-day old chicks

4) Uptake of radioactive iodine

B. Radioimmunoassay

FolliculotropinFollicle Stimulating Hormone (FSH)

ChemistrySame as Thyrotropin (produced by gonadotroph

cells)

Alpha= 92 AA

Beta= 118 AA

Biologic ActionA. Female

1. Stimulates young ovarian follicles to develop multiple layers of granulosa cells & form antra.

Folliculotropin (cont.)

2. Stimulate production of estrogen by developing follicle

B. MaleStimulates the seminiferous tubules-

spermatogenesis

Regulation of releaseConcentration of circulating estrogens- negative

feedback.

Note: Both estrogen production & completed spermatogenesis require LH.

OOGONIA NUMBERS(Text P. 630)

• 5 months of gestation = 7 million

• Birth = 2 million

• Puberty = 300,000 to 400,000

• Released during sexual maturity (40 years) = 480

Corpus albicans

Germinal epithelium

Corpus luteum

Ovulation

Corona radiataSecondary oocyteZona pellucida

Cumulus oophorousTime

Time

Graafian follicle

Antrum

Primary follicle

Growing primary follicle

Primary oocyte

Secondary follicle

ESTROGENS (17 BETA ESTRADIOL)

Biologic Actions

1. Act as “growth hormones” stimulating mitosis in the mammary glands and the female reproductive system (uterus and vagina).

ESTROGENS (cont.)

2. Promote the deposition of fat in the breast, thighs and buttocks, thereby decreasing the specific gravity in females.

3. Promote the early closing of the growth

plates.

epididymisEfferent ductules

Spermatic cord

testis

Seminiferous tubules

Rete testis withinmediastinum testis

Interstitialcells

Germinalepithelial cells

Lumen of seminiferous tubule

Basementmembrane

Spermatazoa

LutotropinInterstitial Cell Stimulating

Hormone (ICSH)

ChemistrySame as Thyrotropin

Half-life of one hour

Alpha=96 AA

Beta=120 AA

Lutotropin (cont.)

Biologic ActionA. Female

1. Release of estrogen from developing follicle.

2. Promotes ovulation. Ovulatory surge in concentration just before ovulation.

3. Affects luteinization of ruptured follicle.

4. Causes release of progesterone from corpus luteum

Lutotropin (cont.)

Biologic ActionB. Male

1. Affects spermatogenesis- completes process.

2. Stimulates Leydig cells to produce testosterone.

Regulation of ReleaseNegative feedback with progesterone

Note: This is why HCG is needed during pregnancy