Hypothalamic & Pituitary Hormones PDF

Hypothalamic & Pituitary Hormones WE MAKE DOCTORS Sonia G. Barreno Rocha MD, PhD Simón Q. Rodríguez Lara MD, PhD Objectives Learn the basic about the hypothalamus-hypophisis-organs endocrin axis. Know the main drugs that are able to interact with this endocr...

Hypothalamic & Pituitary Hormones WE MAKE DOCTORS Sonia G. Barreno Rocha MD, PhD Simón Q. Rodríguez Lara MD, PhD Objectives Learn the basic about the hypothalamus-hypophisis-organs endocrin axis. Know the main drugs that are able to interact with this endocrin axis. Learn the mechanism of action and the adverse effects of drugs able to modify or interact with hypothalamic & pituitary hormones. Hypothalamus – hypophysis – gland signals TRH, CRF, GHRH, GnRH Testosterone T3 & T4 & PIH (dopamine) & DHT IGF-I & IGF-II Estrogen & progestogens Cortisol GH TSH ACTH AVP FSH & LH Prolactin Oxytocin Ritter PCPGKSTMSJM, Flower RJ, Henderson G, Yoon Kong Loke MBBMMD, MacEwan D, Rang HP. Rang & Dale's Pharmacology E-Book: Elsevier Health Sciences; 2018. Universidad Autonoma de Guadalajara, A.C., 2019 4 Koeppen BM, Stanton BA. Berne & Levy Physiology: Elsevier Health Sciences; 2017. GH drugs, Prolactin antagonist, Posterior hypophysis drugs Growth hormone and related drugs Agonist Somatotropin (recombinant GH) Somapacitam (GH analog) Mecasermin (recombinant IGF-1 Oxytocin Hormone Macimorelin (ghrelin agonist) Agonist Oxytocin Antagonist Antagonist Somatostatin analogs Atosiban Somatostatin Octreotide , Lanreotide, Pasireotide Anterior Posterior GH Receptor antagonist Hypophysis Hypophysis Antidiuretic Hormone Pegvisomant Drugs Drugs Agonist Vasopressin Prolactin Antagonist Desmopresin Dopamine Receptor agonist Antagonist Bromocriptine Conivaptan Cabergoline Tolvaptan Quinagolide (non-ergot) Anterior Hypophysis Drugs Mechanism of actions GH Agonist Mechanism of actions Activation and Recruites and activates Binding and phosphorylation of MAP kinases, IR substrates, PI3K, DAG, dimerization of the GHR- PKC, intracelular Ca2+, GHR associated JAK2 STAT transcription tyrosine kinase factors Enzymatic activity, Induction of Growth and transport function, changes mediated metabolism gene expresión by GH Pharmacological effect Somatotropin  Somatostatin mechanism of action Somatostatin binds to Activation of Inward K+ any of the 5 subtypes SST-1 inhibits secretion of GH, prolactin current and inhibition of somatostatin and calcitonin of Inward Ca++ current. receptors. Activation of SST-2 inhibits gastrin, histamine, parietal The SSTRs are 7TM- phosphotyrosine acid secretion; also GH, coupled to “G” protein phosphatase and adrenocorticotropin, glucagon, insulin, receptor´s family. MAPK and interferon-γ The receptor is Decrease the levels of phosphorylated and SST-3 and SST-5 induces reduction of cell cAMP and Intracellular inhibits Adenylyl proliferation and antitumor angiogenesis. Calcium. Cyclase. Somatostatin Pegvisomant Bromocriptine mechanism of action Bromocriptine D2 receptor is a bound to Dopamine 7TM-Coupled to “G” type 2 receptor proteins Activation of the D2 Decrease cAMP and receptor induces intracellular inhibition of calcium. adenylyl cyclase D2 in the Inhibits MAPK tuberoinfundibular mediated by c-Raf pathway inhibits and B-Raf prolactin secretion. Posterior Hypophysis Drugs Mechanism of action Oxytocin Hormone mechanism of action Oxytocin bounds to Calmodulin and Ca++ In uterine smooth its receptor that induce muscle induce belongs to the phosphorylation of contraction 7TMCGP MLCK In epithelial cells The receptor Intracellular Ca++ induce prostacyclin phosphorylates the increase the activity and prostaglandin phospholipase C-β of calmodulin increase inducing secretion In CNS activates PLC interacts with IP3 increase trust, motivate social PIP2 and produce IP3 intracellular Ca++ and participation and and DAG DAG activate PKC group preference. Vasopressin hormone mechanism of action Vasopressin bounds to its The increase of cAMP In epithelial cells induce the receptors that belongs to the activates PKA and receptor activates AC 7TMCGP phosphorylation of AQP-2. In vascular smooth muscle AQP-2 is translocated to the In vascular smooth muscle the receptor phosphorylates apical membrane and induce contraction the phospholipase C-β facilitates the H2O inward PLC interacts with PIP2 and Calmodulin and Ca++ induce produce IP3 and DAG phosphorylation of MLCK IP3 increase intracellular Intracellular Ca++ increase Ca++ and DAG activate PKC the activity of calmodulin Pharmacological applications  Select Hypothalamic and Pituitary Drugs and Their Uses Growth hormone and related drugs Somatropin Pediatric patients who lack adequate endogenous GH secretion, chronic renal insufficiency, Turner syndrome, Noonan Syndrome, Wasting in patients with HIV infection Somapacitan Replacement of endogenous growth hormone in adults with growth hormone deficiency Mecasermin Growth failure in children with severe IGF-1 deficiency unresponsive to growth hormone administration Octreotide Patiens with acromegaly Pegvisomant Acromegaly in patients who are resistant to somatostatin analogs Agents inhibiting prolactin secretion Cabergoline Hyperprolactinemia Posterior Pituitary Hormones and Related Drugs Desmopressin Diabetes insipidus, children with nocturnal enuresis, hemorrhagic conditions Conivaptan Euvolemic and hypervolemic hyponatremia Oxytocin Induce contractions during labor, prevent postpartum hemorrhage, and to stimulate milk let-down in nursing mothers Atosiban Delaying imminent pre-term birth in pregnant adult women Pharmacological adverse effects Somatotropin Adverse effects Leukemia Histiocytosis X Osteogenic Craniopharyngioma Gliobastoma/glioma Astrocytoma sarcoma Diabetes mellitus Intracranial Slipped capital Scoliosis Pancreatitis hypertension femoral epiphysis Mecasermin Adverse effects Antibody production Hypoglycemia Acromegaly  Octreotide adverse effects Hyperglycemia Abdominal distress High blood pressure Nausea  Oxytocin adverse effects Uterine contractions Water intoxication Seizures Vasopressin adverse effects Facial Flushing High blood pressure Xerostomia