PHARMACOLOGY OF PITUITARY HORMONES Flashcards
Define the endocrine system and define hormones
Endocrine system: All the glands of the body and the hormones produced by them.
Hormones: chemical substance of intense biological activity produced by specific cells in the body and transported through the circulation to act on its target cells.
List the sites of hormonal action
Sites of hormonal action:
1. cell membrane receptors- cAMP, IP3/DAG generation, direct transmembrane activation of tyrosine kinase;
2. cytoplasmic receptors;
3. nuclear receptors
How are Anterior pituitary hormones classified?
Anterior pituitary hormones classifiable into:
1. somatotropins consisting of GH & Prolactin.
2. glycoproteins consisting of TSH, FSH, LH.
3. Proopiomelanocortin (POMC) derivatives: Corticotropin (ACTH), α-MSH.
Examples of regulators
- hypothalamic releasing hormones.
2.somatotropin-negative regulator of GH & thyrotropin secretion. - dopamine: inhibits prolactin secretion
What are the hormones of the posterior pituitary gland?
Posterior pituitary:
1. arginine vasopressin
2. oxytocin.
Types of GH and What is the Physiological effects of GH?
Principal form is a 22,000D single polypeptide chain of 191 amino acids.
Smaller form of about 20,000D containing 176 aas.
Stimulation of longitudinal growth of bones.
Increase in bone mineral density after closure of epiphyses.
Stimulation of myoblast differentiation.
Increased muscle mass
Increased GFR
Stimulation of preadipocyte differentiation into adipocytes.
Anti-insulin actions in liver and peripheral tissues.
Development and function of the immune system.
Anabolic and growth-promoting effects mediated through IGF-1
IGF-1 is produced in the liver and other tissues.
IGF-1 receptors are cell surface receptors resembling insulin receptors and has intrinsic tyrosine kinase activity.
IGF-1 receptor can be activated by insulin.
Discuss Growth hormone
Peptide hormone
Principal form is a 22,000D single polypeptide chain of 191 amino acids.
Smaller form of about 20,000D containing 176 aas.
Both have equal bioavailability.
What is the Mechanism of action og GH?
Via GH receptors which are cell surface receptors.
The receptor belongs to the class 1 cytokine receptor superfamily.
It shares structural similarity with receptors for prolactin, erythroprotein, GM-CSF and other interleukins.
Activation of the receptor is triggered by binding of a single GH molecule to two GHR to form a receptor dimer.
This activates autophosphorylation of JAK2.
JAK2 then phosphorylates STAT resulting in modulation of gene expression.
Discuss the Regulation of GH secretion
Secretion is high in children and reaches maximal levels at puberty.
Secretion is highness at night.
Secretion is stimulated by GHRH.
Negative inhibition by GH and IGF-1 and somatostatin.
Secretory stimuli: fasting, hypoglycemia, stress, exercise.
Inhibitory stimuli: corticosteroids, ffa.
What are the uses of GH?
Cases of GH deficiency in children and adults.
Prader-Willi syndrome.
Turner’s syndrome.
CRF (Chronic renal failure) in children.
SGA (small for gestational age) children.
Idiopathic short stature.
Catabolic states: burns, renal failure, osteoporosis, bed-ridden patients.
AIDS wasting syndrome.
Performance enhancer by athletes.
Noonan syndrome
Imbalance of GH results in what?
GH deficiency in childhood results in dwarfism and adiposity.
deficiency in adulthood results in increased mortality from cvs diseases, decreased muscle mass, decreased bone density, impaired psychosocial function.
Excessive secretion results in gigantism and acromegaly.
What is Mecaserin
Mecaserin
Complex of rhIGF-1 and rhIGFBP-3.
Indicated for children with severe IGF-1 deficiency.
It is administered twice daily subcutaneously.
Main adverse effect is hypoglycemia.
Others are intracranial HT, elevated hepatic enzymes.
GH preparations include
Preparations :
Somatropin
Somatrem
Long acting somatropin suspension.
side effects
Injection site pain.
First 8 weeks: intracranial HT, papilledema, visual changes, headaches, nausea/vomiting.
Hypothyroidism, salt and water retention, myalgia, hand stiffness.
Increase incidence of type 2 DM
What are GH antagonists?
Antagonists of GH:
Somatostatin and its analogs.
Pegvisomant.
Dopamine receptor agonists.
These are used in the management of syndromes of GH excess.
Somatostatin analogs
These are ocreotide, lanreotide, vapreotide,seglitide, BIM23268, CH275.
What is Ocreotide (SANDOSTATIN)?
Synthetic derivative of somatostatin.
It is an octapeptide.
Administered s/c 3 times daily.
Binds to SSTR-2 and SSTR-5 receptors.
Peak effect within 30 minutes.
Half-life about 90 minutes.
Duration of action 90 minutes.
It reduces GH secretion and IGF-1 levels.
It also reduces tumor size
It also inhibits thyrotropin secretion and is used for treating thyrotrope adenoma.
Also used for managing GI disorders.
Side effects include nausea, diarrhea, abdominal pain, gallstones.
SANDOSTATIN LAR is a long-acting, slow-release form of ocreotide administered once every 4 weeks via the intramuscular route.
Other uses of ocreotide:
Secretory diarrhoeas associated with carcinoid, cancer chemotherapy, AIDS, diabetes.
Oesophageal bleeding.
For diagnostic imaging (when labelled with indium or technetium) of neuroendocrine tumors such as pituitary adenoma and carcinoids.
