Posterior Pituitary Hormones PDF

Posterior Pituitary Hormones Dr. Sovan Bagchi Professor of Physiology * www.gmu.ac.ae COLLEGE OF MEDICINE  Learning Objectives Describe its synthesis and of s...

Posterior Pituitary Hormones Dr. Sovan Bagchi Professor of Physiology * www.gmu.ac.ae COLLEGE OF MEDICINE  Learning Objectives Describe its synthesis and of storage Vasopressin Describe the mechanisms by which vasopressin binds to cells and by which vasopressin stimulates vasoconstriction and renal water reabsorption Describe the regulation of vasopressin release Describe oxytocin synthesis, sites of production, and storage Identify the cellular binding and major physiological actions of oxytocin Describe the regulation of oxytocin release  Pituitary gland or Hypophysis It is about 1 cm Dia and 0.5 to 1 gm in weight. Located in the bony cavity called Sella turcica at the base of brain. It is connected with hypothalamus with hypophysial stalk. Pituitary can be subdivided into 1. Anterior pituitary (Adenohypophysis) and 2. Posterior pituitary (Neurohypophysis)  Embryologically, the 2 portions of the pituitary originate from different sources Anterior pituitary - pharyngeal epithelium & Posterior pituitary - neural tissue 6 hormones are secreted from anterior pituitary - GH, ACTH, TSH, LH, FSH & PRL Posterior pituitary secretes Vasopressin and Oxytocin Posterior pituitary or Neurohypophysis  Posterior pituitary Oxytocin and vasopressin are polypeptides and contain 9 amino acids. They are almost identical hormones. Oxytocin Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-GlyNH2 Vasopressin: Cys-Tyr-Phe-Gln-Asn-Cys-Pro-Arg-GlyNH2 Transportation and release Due to similarities in structure, they have functional similarities. Oxytocin is primarily formed by paraventricular nuclei and ADH is primarily formed by supraoptic nuclei of hypothalamus. They are transported to posterior pituitary by hypothalamo- hypophysial tract. They are transported in combination with carrier protein called neurophysin. Vasopressin critical A neuropeptide in maintaining hormone of the blood pressure and posterior pituitary serum osmolality.  Case VR, a 50-year-old female, comes to your office with mild confusion. She says she cannot keep track of dates and sometimes forgets names. She is being treated with chemotherapy for metastatic melanoma in her brain, but her confusion was not present before or during the first weeks of chemotherapy. After examining her and ordering routine blood tests, you find that her blood concentration (blood osmolality) is severely low, indicating excess water in her body. You hypothesize that the metastatic tumor is secreting the hormone vasopressin (ADH), causing the low osmolality. Transport and Receptor Binding It binds to target tissues by using the various vasopressin receptors (V1A, V1B, V2)  Blood Vessels: Vasoconstriction Vasopressin V1A receptors, Clinical correlation Vasopressin, along with agents such as dopamine and norepinephrine, can be used pharmacologically in intensive care units to raise the blood pressure in patients who are hypotensive. It also can be used to vasoconstrict Stimulates smooth muscle contraction, bleeding blood vessels like esophageal or gastric constricting the arteriole varices Raising blood pressure Renal Water Reabsorption CLINICAL CORRELATION Urine concentration decreases in diabetes insipidus, because of either a lack of ADH (eg, a brain tumor) or lack of renal response to ADH (damage to ADH receptors in kidney disease). These patients develop abnormal polyuria (high urine flow) with very dilute urine.  Other functions Adrenocorticotropic Hormone Release Platelet Aggregation Vasopressin V1A receptors (vascular endothelial cells) V1B receptors (Pituitary) Release von Willebrand factor Stimulates platelet aggregation and blood ACTH clotting Because of this mechanism, vasopressin is used Cotisol pharmacologically to stop abnormal bleeding in patients with chronic kidney disease who sometimes have platelet dysfunction Maintain BP  Inhibition Regulation of Vasopressin Cortisol inhibits ADH release by the pituitary, and ANP inhibits the effect of ADH on the renal collecting duct Oxytocin Case You are counseling LO, a 25-year-old pregnant patient, about the benefits of breastfeeding. You explain that in addition to lowering rates of morbidity in both infants and mothers, breastfeeding also reduces maternal depression and improves maternal-newborn bonding. LO’s mother, who chose to bottle-feed her own children, seems skeptical. “I don’t know if I believe that. How could that be affected by breastfeeding? How do you know that it isn’t just that women who breastfeed think they’re happier and bonding better? I didn’t breastfeed and I still love my babies.” How will you answer her questions about breastfeeding and bonding?  Transport and Receptor Binding After synthesis in the hypothalamus as a water-soluble peptide, oxytocin travels unbound in circulation. It binds to target tissues by using the oxytocin receptor, a G protein– coupled receptor (breast and brain). After oxytocin binds to its receptor, mitogen-activated protein (MAP) kinase is activated Initiates a signaling cascade that leads to altered gene expression. How Oxytocin Acts!  Role of Oxytocin During the third trimester During the first stage of labor Oxytocin pulsations increase threefold to Oxytocin receptor expression in the fourfold, causing strong uterine uterus increases in response to rising contractions that push the fetus down estradiol levels, and the uterus toward the cervix. becomes more responsive to this Cervical dilation during labor activates hormone, in preparation for labor stretch receptors and stimulates a positive feedforward neurogenic reflex that further stimulates the hypothalamus to secrete oxytocin. The elevated oxytocin levels advance the mother’s labor by promoting additional contraction of the uterus. This positive feedback will continue until the infant is delivered and the increased uterine pressure and stretch is resolved  Clinical Correlation Pitocin is the synthetic form of oxytocin that is administered intravenously to initiate labor or to cause stronger contractions and hasten delivery. It is also the drug of choice for postpartum hemorrhage, because increasing uterine muscle tone slows excess bleeding 20  Role of oxytocin after Delivery Oxytocin release causes continued uterine contractions in the early postpartum period. This is beneficial in helping the uterus return to its pre- pregnancy size How oxytocin Acts  Actions on the Breast Effect on milk ejection Suckling stimuli of breast goes through sensory nerve to supraoptic and paraventricular nuclei. Stimulation of those nuclei cause more secretion of oxytocin. Oxytocin cause contraction of myoepithelial cells which contain the alveoli where breast milk is stored. This contraction initiates milk ejection by releasing milk into lactiferous ducts and then into the lactiferous sinus Actions in the Central Nervous System Hypothalamus Basal Ganglia. The general effect is to reduce Oxytocin also stimulates the the stress response through ventral striatum, adjacent to the CRH-ACTH-Cortisol Axis nucleus accumbens Oxytocin’s general function for Feelings of love, anticipation, promoting nurturing and and interpersonal social rewards bonding behaviors activate the ventral striatum, Amygdala which mediates processing of motivation and reward Oxytocin reduces activity in the amygdala (Reduces fear, anxiety, and aggression) Other Behavioral Effects Maternal-Fetal Bonding. It may reinforce monogamy and lifelong partnering, and it reinforces feelings of trust and empathy Motivation and Reward. work with serotonin to encourage pleasurable behaviors as eating and sexual activity Group Decision-Making and Teamwork Improves group decision-making and teamwork But, when released in stressful situations, oxytocin may promote anxiety and fear and avoidance of certain activities Negative Memories Oxytocin may also intensify negative memories  Behavioral Release Dampen the stress associated with pain. Importance in clinical pain management Sexual Stimulation and Orgasm Hormone levels rise during sexual activity, an effect partially mediated by estrogen  Learning Resources Textbook: John E. Hall and Michael E. Hall. Textbook of Medical Physiology. 14th ed. Elsevier. 2021. ISBN: 978-0-323-59712-8. Chapter: 75 Page no. 915-927 Power-point presentation in the moodle January 24, 2025 www.gmu.ac.ae COLLEGE OF PHARMACY