optic chasm infudibulum arterial blood supply hypothalamo-pituitary portal vessels anterior...
TRANSCRIPT
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