Hypothalamic-Pituitary Axis (PDF)

Hypothalamus-Pituitary Axis Kamran Ali National Teaching Fellow PhD MMEd BDS (Hons) FDSRCS FCPS FFDRCSI FFDTEd FDSRCPS PFHEA Professor / Consultant in Oral Surgery Aim To gain an understanding of the hormones secreted by the hypothalamus and pituitary gland Objectives By the end of the session you s...

Hypothalamus-Pituitary Axis Kamran Ali National Teaching Fellow PhD MMEd BDS (Hons) FDSRCS FCPS FFDRCSI FFDTEd FDSRCPS PFHEA Professor / Consultant in Oral Surgery Aim To gain an understanding of the hormones secreted by the hypothalamus and pituitary gland Objectives By the end of the session you should be able to discuss the following aspects of hypothalamic and pituitary hormones: Chemistry Synthesis Functions Control Common disorders Introduction Hypothalamic-Pituitary (Hypophyseal) Axis Anterior pituitary cells and hormones Cell type Pituitary population Product Target Somatotrophs 40-50% GH All tissues; Liver Corticotrophs 15-20% ACTH Thyrotrophs 3-5% TSH Adrenal gland Adipocytes Melanocytes Thyroid gland Gonadotrophs 10-15% LH FSH Gonads Lactotrophs 10-15% PRL Breasts, Gonads Hypothalamic-Hypophyseal Portal System Hypothalamic neurohormones act on adenohypophysis to stimulate or inhibit synthesis & release of anterior pituitary hormones Hypothalamic Hormone Effect on Anterior Pituitary Corticotropin releasing hormone (CRH) Stimulates ACTH secretion Thyrotropin releasing hormone (TRH) Stimulates TSH and Prolactin secretion Growth hormone releasing hormone (GHRH) Stimulates GH secretion Somatostatin Inhibits GH Gonadotropin releasing hormone (GnRH) a.k.a LHRH Stimulates LH and FSH secretion Prolactin inhibiting hormone Inhibits PRL secretion Growth Hormone Somatotropin Somatotropic Hormone ⚫ Small protein with 191 amino acids in a single chain GH: Effect on Growth ⚫ Causes growth of almost all tissues of body  size of cells  mitosis thereby  no. of cells ⚫ Exerts most of its effects on growth via Somatomedins (IGF) GH: Effect on Protein Metabolism  Synthesis of proteins  Breakdown of proteins ⚫ ⚫ ⚫ ⚫ Enhances AA transport across cell membrane Enhances DNA transcription Enhances RNA translation Spares proteins by reducing protein catabolism GH: Effect on Fat Metabolism  breakdown of FA from adipose tissue  conversion of FA into acetyl-CoA in all tissues with subsequent utilization for energy May cause  acetoacetic acid (ketosis) & lead to a fatty liver GH: Effect on Carbohydrate Metabolism  utilization of glucose for energy Decreased uptake of glucose by cells including muscles and adipose tissue  Leads to increased blood glucose levels resulting in increased insulin secretion – may burn  cells and produce a diabetogenic effect (pituitary diabetes) GH: Correlation With Glucose & Insulin ⚫ GH fails to cause growth in the absence of glucose or insulin ⚫ Remember insulin promotes transport across cell membrane of several AA required for growth GH: Rate of Secretion ⚫ Continues throughout life, even though rate of secretion decreases with age Child / Adolescent 20-40 Y 40-70Y 6ng/ml 3ng/ml 1.6ng/ml (Aging?) May rise to as high as 50ng/ml in prolonged starvation Characteristically rises in the 1st 2h of deep sleep GH: Regulation ⚫ ⚫ ⚫ ⚫ ⚫ ⚫ Starvation especially with severe protein deficiency Hypoglycemia Low concentration of FA in blood Exercise Excitement Trauma GH Regulation: Hormonal Factors ⚫ Stimulation ⚫ GHRH (Polypeptide) ⚫ Catecholamines ⚫ Dopamine ⚫ Serotonin ⚫ Inhibition ⚫ GHIH - Somatostatin (Polypeptide 14 AA) Also secreted by islet cells, GIT, CNS etc Disorders of GH: Gigantism & Dwarfism At 8’9″, Sultan Kösen, from Turkey, is the tallest man in the world. At 21 and a half inches, Chandra Bahadur Dangi, from Nepal, is the shortest Acromegaly Hyperpituitarism: Features ⚫ Diabetes mellitus (Increased levels of GH) ⚫ Hypertension (Increased levels ACTH) ⚫ Goitre (Increased levels TSH) GH Hyposecretion: Features ⚫ Hypothyroidism ⚫ Risk of adrenal crisis Oxytocin Chemistry: Nonapeptide ⚫ Synthesized in the cell bodies of hypothalamic neurons Oxytocin: Actions ⚫ Powerfully stimulates the gravid uterus toward end of gestation, causing delivery ⚫ Helps expression of milk from breast alveoli into ducts facilitating suckling ⚫ No role in breast development Antidiuretic Hormone ⚫ Synthesized as pre-prohormone & processed into a nonapeptide ⚫ Synthesized in the cell bodies of hypothalamic neurons ⚫ Stored in the neurohypophysis ADH: Actions ▪ Conserves body water & regulates tonicity of body fluids Reabsorption of salt-free water from distal renal tubules and collecting ducts - Antidiuresis ▪ At higher concentration, constricts the arterioles - Vasopressin ADH Secretion & Plasma Volume Secretion of ADH— hemodynamic control ⚫ ADH is stimulated by a decrease in blood volume, cardiac output, or blood pressure ⚫ Hemorrhage is a potent stimulus of ADH release ⚫ Activities, which reduce blood pressure, increase ADH secretion ⚫ Conversely, activities or agents that increase blood pressure, suppresses ADH secretion ADH & B.P. ADH Deficiency: Diabetes Insipidus ⚫ Inability to produce concentrated urine a hallmark of ADH deficiency diabetes insipidus - may result from head injury ⚫ May cause Xerostomia Summary Further Reading 1. Ali K & Prabhakar E (2019) Essential Physiology for Dental Students. Ist Ed. Wiley Blackwell. ISBN: 978-1-11927175-8 2. Marieb, E. & Keller, S. (2017). Essentials of human anatomy and physiology. 12 th ed. Pearson. ISBN: 9781292216119