The Pituitary Gland - 2025 PDF

The Pituitary Gland Viveiros | 2025 Pituitary Gland (1) The pituitary gland secretes several essential hormones Hypothalamus (Oxytocin, ADH, GH....) Short-loop feedback Neurohormone...

The Pituitary Gland Viveiros | 2025 Pituitary Gland (1) The pituitary gland secretes several essential hormones Hypothalamus (Oxytocin, ADH, GH....) Short-loop feedback Neurohormone signal (2) It’s a critical component of Pituitary the HPA, which regulates Gland GH - PRL hormone secretion from several Long-loop feedback endocrine glands Trophic signal hormone Disruption of pituitary gland Thyroid Adrenal Cortex function can lead to different Gonads endocrine disorders Thyroid hormones, Steroids Endocrine based disorders that are caused by pituitary gland dysfunction Diabetes Insipidus (‘water’ diabetes): ADH Pituitary Diabetes Insipidus (Central or Neurogenic DI) Hyper- and Hypothyroidism: Disruption of TSH and Thyroid hormone Cushing’s Disease: ACTH and Cortisol Secondary Addison’s Disease: ACTH, Cortisol, Aldosterone astraitrate Acromegaly and Dwarfism: Disruption of Growth Hormone (GH) Infertility / Delayed onset of Puberty: Disruption of gonadotrophins (LH & FSH) and sex steroid hormones (Estradiol, Testosterone and Progesterone) Topic Outline 1. Pituitary gland development 2. Anatomy: Posterior and Anterior Pituitary (differences) 3. Major Hormones Produced P-N-2 (Posterior - Neural - 2 Hormones) A-E-6 (Anterior - Endocrine - 6 Hormones) 4. Regulation of hormone synthesis and secretion The Hypothalamic-Pituitary Axis The Hypothalamic-pituitary vascular portal system Negative feedback loops 5. Target glands and physiological function 6. Causes & consequences of pituitary gland dysfunction Pituitary Gland (Hypophysis) Sphenoid Bone of the skull –features the sella turcica: a protective pocket for the pituitary gland The pituitary is a small gland located at the base of the brain Two major components *Greek: ‘Adeno’ - gland Anterior Lobe: Adenohypophysis* ‘Hypo’ - under Posterior Lobe: Neurohypophysis ‘Physis’ - growth Pituitary Gland Development The pituitary gland is derived Diencephalon from two sources during early embryonic development Rathke’s pouch The posterior lobe arises from developing brain: neuroepithelium of the Diencephalon we The anterior lobe (..and intermediate) arises from an out-pocketing of epithelium in Anterior Posterior the oral cavity called Rathke’s Pouch endoor The Pituitary: two parts with distinct cellular composition and function Divisions of the Pituitary Anterior Pituitary Anterior Posterior 3 2 1 Posterior Pituitary 1. Anterior lobe (Endocrine) 2. Posterior lobe (Neural cells) 3. Stalk Pituitary gland hormone secretion is dependent on signaling from the hypothalamus Communication is facilitated by … (1) Hypothalamic neurons that project into the posterior pituitary (2) The hypothalamic-portal (vascular) system to the anterior pituitary  Neurohypophysis: Posterior Pituitary (PN2) Stores and secrete two key hormones 1. Oxytocin Uterine Muscles Mammary Glands 2. Antidiuretic Hormone (ADH) * (Vasopressin) Kidney Tubules * PN2: Posterior - Neural - 2 Hormones Posterior pituitary hormone production Oxytocin and ADH are synthesized in cell bodies of neurosecretory neurons within the supraoptic (ADH) and paraventricular (Oxytocin) nuclei of the hypothalamus These hormones are stored in the axon terminals (Herring bodies) in the posterior pituitary Released in response to an action potential that travels along the axon. Enter the circulation Stimulation of hormone release Action potentials along the neurons stimulate hormone release into the posterior pituitary –which then enter the capillary network for release into the systemic circulation (1) Oxytocin Very small peptide Function (9 amino acids) Stimulates myoepithelial cell Greek: ‘rapid birth contractions In the uterus during parturition In the mammary gland during lactation to promote milk ejection 1909: Identified by Sir Henry H. Dale Showed that pituitary extract would: Mammary Gland section: (1) Contract the uterus of pregnant cats Myoepithelial cells (2) Promote milk release Luminal epithelial cells Mark LaBarge, Berkely By 1911 doctors using pituitary extracts to promote contractions during labor Other functions … regulation of natriuresis (sodium excretion by the kidney) cardiovascular homeostasis social and sexual behavior (a) Oxytocin control of milk ejection from the mammary gland Suckling is the major stimulus for oxytocin release Sensory receptors in the nipple connect with nerve fibers to the spine, then impulses are relayed to the brain to the hypothalamus and activate oxytocin neurons to stimulate hormone release Hypothalamus DA Anterior Posterior pituitary pituitary Myoepithelial Cell PROLACTIN OXYTOCIN Mammary Gla nd milk gland Myoepithelial cells Cells Milk Synthesis Milk Ejection Alveolus of Mammary Gland  mammary gland Oxytocin stimulates myoepithelial cell contractions in the mammary gland during lactation to promote milk ejection Neural Blood P.L. Senger, 2012 Oxytocin levels (blood) in “Conditioned response”: response to suckling oxytocin release in response to stimuli associated with suckling (b) Oxytocin control of uterine contractions Reflexes originating in the cervix and uterus stimulate oxytocin synthesis and release via neural input to the hypothalamus Oxytocin levels increase in plasma at the time of parturition Oxytocin promotes uterine smooth muscle contractions to deliver the fetus P.L. Senger, 2012 Positive feedback Positive feedback control that control of oxytocin amplifies responses release during parturition is need for uterine smooth muscle contractions to + Endocrine Cell deliver the fetus Biological Response Hormone Target Cell + (Ex. Oxytocin secretion during parturition) Positive feedback regulation of oxytocin secretion Uterine Contraction: Oxytocin stimulates the uterus to contract and causes the cervix to stretch. Increased cervical * stretch is sensed by neurons in * the cervix and transmitted to the hypothalamus, which signals more oxytocin secretion Milk Ejection: Oxytocin secreted in response to suckling forms an open loop feedback system in which positive input is interrupted when suckling stops Milk Ejection Uterine Contraction suckling (2) Anti-Diuretic Hormone (ADH) …also called Vasopressin Very small peptide hormone (9 amino acids) similar to oxytocin (….differs only by 2 a.a.) Vasopressin was originally isolated from pigs The human hormone is referred to as Arginine Vasopressin (AVP) because it has an arginine in position 8 instead of the lysine in the pig hormone Anti-Diuretic Hormone (ADH) Function kidney 1. Functions to Control Water Balance ADH is released when the body is dehydrated Promotes increased permeability to water in the distal tubules and collecting ducts of the nephrons in the kidneys Causes the kidneys to conserve water (anti-diuresis) -Concentrates urine (increased osmolality) -Decreases volume (reduced water excretion) 2. Promotes Vasoconstriction (in higher concentrations) Promotes vascular smooth muscle contraction Increases blood pressure Factors that promote ADH secretion (1) HIGH plasma osmolarity (concentration of solutes in blood), detected by osmoreceptors in the hypothalamus (2) LOW blood volume* and pressure, detected by receptors in the heart & large arteries *Not as sensitive a stimulator as osmolarity, but potent in severe conditions such as hemorrhage. Ex. 15-10% of blood loss leads to high ADH secretion. ADH-Vasopressin Receptors 3 subclasses of ADH receptors identified in humans Referred to as Arginine VasoPressin Receptors (AVPR) All are G-coupled receptors -can activate different secondary messengers Receptor 1A Receptor 1B (activate phospholipase C) Receptor V2 (activates adenylate cyclase) Tissue Distribution Function 1A: vascular smooth muscle Vasoconstriction 1B: brain Neural V2: kidney tubules, fetal lung Water re-absorption ADH (Vasopressin) controls water re-absorption in the kidney kidney V2 receptors (AVPR2) for ADH are highly expressed in the epithelial cells of the kidney distal tubule and collecting duct on the nephron  ADH-receptor binding activates adenylate cyclase and increases cAMP levels (second messenger in the cell) Elevated cAMP promotes the insertion of water channels (Aquaporin-2) in the epithelial cell membrane and transcription of the aquaporin-2 gene (AQP2) This increases permeability and water is re-absorbed from the forming urine back into the circulation (concentrates urine) ADH regulation of water balance 1 ADH binds to 2 Receptor activates cAMP 3 Cell inserts AQP2 water 4 Water is absorbed by membrane receptor second messenger system pores into apical membrane osmosis into the blood Nephron Aquaporin (AQP2) water channel Regulation of ADH (Vasopressin) Secretion Water Balance: Increased blood osmolality or decreased blood volume are sensed in the brain or thorax, respectively, and increase ADH (vasopressin) secretion ADH, acts principally on the ADH kidney to increase water reabsorption, which restores osmolality and volume. This prevents further secretion by a negative feedback Plasma volume Plasma osmolarity Disruptions in either… (1) ADH hormone levels, or the (2) Response to ADH ….leads to problems in the regulation of water balance Diabetes Insipidus (DI) …‘water’ diabetes 1.Pituitary Diabetes Insipidus caused by a deficiency in ADH Also referred to as Central or Neurogenic DI Other types of Diabetes Insipidus 2. Gestational DI (Reduced ADH during pregnancy) 3. Nephorgenic DI (Kidneys do not respond to ADH) 4. Primary Polydipsia (Excess fluid intake reduces ADH) Major clinical features: Excessive thirst (drinking) Excretion of large volumes of dilute urine (not increased by fluid intake) Major distinction with Diabetes Mellitus (‘sugar’ diabetes) Absence of.. 1. Hyperglycemia (elevated blood glucose) 2. Glycosuria (excess glucose in the urine) Possible (diagnostic) analysis for DI Blood Analysis Glucose Levels Electrolyte levels Hypernatremia: High sodium, as dehydration develops Urine Analysis Dilute urine with low specific gravity Osmolatity and electrolyte levels are generally low Fluid Deprivation Test helps to determine if the DI is caused by Excessive intake of fluid (polydipsia) Q: What happens to A defect in ADH production/secretion urine output ? A defect in kidney response to ADH Possible (diagnostic) analysis for DI Fluid Deprivation Test Excessive intake of fluid (polydipsia) *Remove fluids ----- Expected response? A defect in ADH production/secretion *Remove fluids ----- Expected response? A defect in kidney response to ADH *Remove fluids ----- Expected response? Q: How to distinguish between (i) deficiency of ADH & (ii) lack/poor response to ADH? Causes of Diabetes Insipidus ….. (1) Pituitary/Central DI Deficiency or lack of ADH production/secretion Pituitary Tumor, Head injury, Infection Treatment: controlled by administering ADH/vasopressin (2) Nephrogenic DI Inability of the kidneys to respond to ADH Genetic defect, Certain drugs (lithium), Kidney Disease (ex. polycystic kidneys), Hypercalcemia Treatment: controlled by fluid intake & drugs to lower urine output (3) Dipsogenic DI (Primary Polydipsia) Excessive intake of fluid Defect in thirst regulation (in the hypothalamus) Risks of Pituitary/Central DI Dehydration Electrolyte imbalance Nephrogenic (Congenital) Diabetes Insipidus ADH production and secretion is normal, but the kidneys fail to respond to ADH Associated with mutations in the V2 Receptors for ADH >200 mutations (loss of function mutations) in the AVPR2 gene have been identified in people with nephrogenic DI … ADH receptor mutations also identified in dogs “A low affinity vasopressin V2-receptor in inherited nephrogenic diabetes insipidus“ Luzius et al, 1992. Journal of Receptor Research 12 (3) 251-68 “Successful long-term treatment of congenital nephrogenic diabetes insipidus in a dog“ Takemura N., 1998 Journal of Small Animal Practice 39(12) 592-4 NSIAD: Nephrogenic Syndrome of Inappropriate Anti-Diuresis Two mutations in in the AVPR2 gene lead to constitutive V2 receptor activation (…even in the absence of ADH) Leads to the constant re-absorption of large amounts of water, regardless of fluid intake (1) Hypo-natremia: low electrolyte (salt) levels (2) Hypo-osmolality: abnormally dilute blood serum Learning objectives  Know which tissues give rise to the pituitary gland  Understand the key differences between the posterior and anterior pituitary  Explain how the hypothalamus regulates pituitary gland hormone synthesis and secretion  Explain feedback control of hormone secretion  Know the hormones secreted by the posterior pituitary gland and their function  Describe how disruptions in pituitary gland function lead to specific endocrine disorders.. Diabetes Insipidus