PITUITARY AND HYPOTHALAMIC HORMONES OUTLINE

1. BIOMEDICAL IMPORTANCE
a. LOSS OF ANTERIOR PITUITARY FUNCTION (PAN-HYPOPITUITARISM) RESULTS IN THE ATROPHY OF THE
i. Thyroid
ii. Adrenal cortex
1. PERSONAL COMMENTARY/IES
a. remember that ANGII and K-ion act as trophic factors for adrenal cortex’ zona
glomerulosa (as such only the two other zona’s will experience atrophy)
iii. Gonads
2. HYPOTHALAMIC HORMONES REGULATE THE ANTERIOR PITUITARY
a. RELEASE OF HORMONE IS AT LEAST UNDER TONIC CONTROL OF AT LEAST ONE HORMONE
b. WHERE ARE THESE RELEASING HORMONE (RH) RELEASED?
i. From the hypothalamic nerve-fiber endings
ii. Specifically around the capillaries of the hypothalamic-hypophyseal system in the pituitary
stalk
c. HOW WILL IT REACH ITS TARGET GLAND (THE PITUITARY)?
i. Via the special portal system
d. BY WHAT MANNER ARE THEY BEING RELEASED?
i. Pulsatile manner
ii. They respond better to pulsatile rather than continuous stimulation
e. WHAT CONTROLS THE RELEASE OF LH AND FSH
i. Gonadotropin Releasing Hormone (GnRH)
f. WHAT REGULATES GNRH?
i. Circulating levels of gonadal hormones (FSH and LH, via feedback mechanism)
g. WHAT CONTROLS THE RELEASE OF ACTH?
i. Corticotropin Releasing Hormone (CRH)
h. IF CRH CONTROLS THE RELEASE OF ACTH, WHAT REGULATES THE RELEASE OF CRH?
i. Cortisol
i. WHAT IS THE STIMULUS FOR THE RELEASE OF THYROID STIMULATING HORMONE (TSH)?
i. Thyroid Releasing Hormone (TRH)
ii. TRH has a similar effect on the prolactin gene (p. 551)
j. WHAT INHIBITS THE RELEASE OF TSH?
i. Somatostatin (a GH inhibiting hormone, AKA Anti-GH hormone)
k. WHAT IS THE OTHER NAME OF SOMATOMEDIN-C
i. Insulin-like Growth Factor I (IGF-I)
l. WHAT ARE THE EFFECTS OF SOMATOMEDIN-C OR (IGF-I)
i. Stimulates the release of Somatostatin (Growth Hormone Release Inhibiting Hormone, GHR-IH)
ii. Inhibits release f GH-RH
m. WHAT IS THE ROLE OF GONADOTROPIC-ASSOCIATED PEPTIDE (GAP)?
i. A potent inhibitor of Prolactin (PRL)
n. WHAT ARE THE HYPOTHALAMIC HORMONES FOUND IN THE NERVOUS SYSTEM?
i. TRH
ii. CRH
iii. Somatostatin
o. WHAT IS THE CLOSEST MECHANISM TO THAT OF GNRH AND TRH?
i. Calcium-phosphatidylinositol mechanism

3. THE ANTERIOR PITUATRY PRODUCES MANY HORMONES THAT STIMULATE VARIOUS PHYSIOLOGIC
PROCESSES
a. Let’s discuss the mechanism
i. Mechanism of synthesis and with intracellular mediators allows the classification of hormones
into THREE categories:
1. Growth Hormone, Prolactin, and Chorionic Somatomammotropin/Human Placental
Lactogen Group (GH-PRL-CS Group)
2. Glycoprotein Group
3. Pro-opiomelanocortin peptide family
b. LET’S DISCUSS THE COMMON FEATURES
i. What are the common typical features of these group?
1. Single tryptophan residue
2. Two (2) homologous disulfide bonds
3. Homology
a. hGH and hCS = 85%
b. hGH and PRL = 35%
Pituitary and Hypothalamic Hormones. Outlined by ECJ Lim, Ph.B., BSN, RN, RM, MN, USRN page 1 of 4
 4. All three (3) has common activities for
a. Growth
b. Lactogenesis
5. Site of production
a. GH and PRL = Anterior Pituitary Gland
b. CS = Syncytiotrophoblast of Placenta)
4. LET’S NAME THE SUBCOMPONENTS OF EACH OF THE FAMILY (REMEMBER WE HAVE 3)
a. GROWTH HORMONE, PROLACTIN, AND CHORIONIC SOMATOMAMMOTROPIN/HUMAN PLACENTAL
LACTOGEN GROUP (GH-PRL-CS GROUP
i. Growth Hormone
ii. Prolactin
iii. Chorionic Somatomammotropin/Human Placental Lactogen
b. GLYCOPROTEIN GROUP
i. TSH
ii. LH
iii. FSH
iv. CG
c. PRO-OPIOMELANOCORTIN PEPTIDE FAMILY (POMC)
i. ACTH
ii. LPH
iii. MSH
5. LET’S DISCUSS THE INDIVIDUAL FAMILIES, REMEMBER WE HAVE 3
a. The GH-PRL-CS Family
i. GROWTH HORMONE
1. Synthesis and Structure
a. Synthesized from
i. Somatotropes
b. Most abundant cells in the gland
c. Concentration of GH in pituitary
i. 5-15 mg/g
2. The GH Receptor
a. Cytokine-hematopoietin receptor superfamily
b. Single spanning domain
c. What happens to GH binding?
i. Causes the DIMERIZATION of two (2) GH receptors
ii. This results in the
1. Activation of the GH-receptor associated JAK-2 tyrosine kinase
and
2. Phosphorylation of the receptors and JAK2 on tyrosyl residues
d. These would result in the activation of number of signalling pathways
i. STAT protein
ii. SHC/Grb2-associated activation of the MAP kinase pathway
iii. IRS Phosphorylation with activation of PI3 kinase
iv. PLC activation with production of DAG and activation of PKC
e. What is PECULIAR to this mechanism
i. JAK Kinase pathway
3. Physiologic and Biochemical Actions
a. GH is essential for postnatal growth and for normal carbohydrate, lipid,
nitrogen, and mineral metabolism
b. What mediates the growth-related effects
i. IGF-I
c. Structurally this GH is similar to what structure?
i. Proinsulin
d. Another closely related peptide found in human plasma, aside from insulin
i. IGF-II
e. Compare and Contrast IGF-I and IGF-II
i. IGF-1
1. 70 amino acids
2. Correlates most directly with GH effects
3. Individuals who lack this (IGF-1, but have IGF-II), fail to grow
ii. IGF-2
1. 67 amino acids
2. Plasma levels, twice that of IGF 1
f. ACTIONS OF GH
Pituitary and Hypothalamic Hormones. Outlined by ECJ Lim, Ph.B., BSN, RN, RM, MN, USRN page 2 of 4
 i. PROTEIN SYNTHESIS
1. Increase transport of amino-acid nucleus
2. Animals treated with GH shows positive (+) nitrogen balance
3. Similarity with insulin
a. It increases RNA/DNA synthesis in some tissues
ii. CARBOHYDRATE METABOLISM
1. Antagonizes the effects of insulin
2. Hyperglycaemia therefore results after prolonged
administration of GH
3. Prolonged treatment can lead to diabetes mellitus (secondary
to insulin suppression)
iii. LIPID METABOLISM
1. Promotes release of free fatty acids
2. Causes increased oxidation of free fatty acids in the liver
3. Increased ketogenesis may occur for client with insulin
deficiency (DM)
iv. MINERAL METABOLISM
1. more likely IGF-I promotes positive
a. calcium (remember it stimulates growth, especially
bone, prior to the closure of epiphyseal plates)
b. magnesium
c. phosphate
2. causes retention of Na, K, and C
v. PROLACTIN-LIKE EFFECTS
1. Binds to lactogenic receptors
2. Has many properties of prolactin such as
a. Stimulation of mammary glands
b. Lactogenesis
4. Pathophysiology
a. Laron-type dwarf
b. Pygmies
c. Gigantism
d. Acromegaly
ii. PROLACTIN
1. Synthesis and Structure
a. Secreted by Lactotropes
b. Acidophilic cells of anterior pituitary
2. The PRL Receptor
a. Similar in size to GH receptor
b. Has single spanning domain (like GH)
3. Physiologic and Biochemical Actions
a. Involved in the initiation and maintenance of lactation in mammals
b. Excessive levels can trigger breast development in ovariectomized females
and males (gynecomastia)
c. Capable of maintaining the corpus luteum, thus AKA luteotropic hormone
d. Intercellular mediator of PRL is unknown
4. Pathophysiology
a. Tumours of prolactin causes
i. Amenorrhea
ii. Galactorrhea
iii. Gynecomastia
iv. Impotence (in men)
iii. CHORIONIC SOMATOMAMMOTROPIN/HUMAN PLACENTAL LACTOGEN
1. Synthesis and Structure
a. Final member of GH-PRL-CS family
b. No definite function in humans
c. Lactogenic and luteotropic activity
d. Metabolic effects are qualitatively similar to those of growth hormones
i. Inhibition of glucose update
ii. Stimulation of free fatty acid
iii. Glycerol release
iv. Enhancement of nitrogen and calcium retention
b. The GLYCOPROTEIN Group (Most complex protein hormones)
i. FSH
Pituitary and Hypothalamic Hormones. Outlined by ECJ Lim, Ph.B., BSN, RN, RM, MN, USRN page 3 of 4
 1. Bids to specific receptors on plasma membranes
2. Target cells
a. Follicular cells in ovary;
b. Sertoli cells in testis
3. Intracellular Signalling
a. Adenylyl cyclase and increase cAMP production
ii. LH
1. Binds to specific plasma membranes
2. Target cells
a. Corpus Luteum to produce progesterone
b. Leydig cells to produce testosterone
3. Intracellular Signalling
a. cAMP
b. enhanced
i. conversion of acetate to squalene (precursor for cholesterol synthesis)
ii. conversion of cholesterol to pregnenolone
4. prolonged exposure to LH results in desensitization (hence, ideal way of birth control)
iii. HCG
1. Glycoprotein
2. Synthesized by Syncytiotrophoblast cells
3. Has ab dimer
4. Closely resembles LH
5. Increase in blood and urine shortly after implantation
iv. TSH
1.
Glycoprotein
2.
Dimer of ab
3.
Binds to plasma membrane rectors and activates adenylyl cyclase
4.
Long term metabolic effects of TSH are due to production and action of thyroid
hormones
c. PRO-OPIOMELANOCORTIN PEPTIDE FAMILY (POMC)
i. ACTH
1. Synthesis and Structure
2. The ACTH Receptor
3. Physiologic and Biochemical Actions
4. Pathophysiology
ii. LPH
1. Synthesis and Structure
2. The LPH Receptor
3. Physiologic and Biochemical Actions
4. Pathophysiology
iii. MSH
1. Synthesis and Structure
2. The MSH Receptor
3. Physiologic and Biochemical Actions

BIBLIOGRAPHY

Darryl K. Granner, MD, Harper’s Biochemistry 25th Edition.

Pituitary and Hypothalamic Hormones. Outlined by ECJ Lim, Ph.B., BSN, RN, RM, MN, USRN page 4 of 4