BS31019 - Lecture 1.2 - The Hypothalamic-pituitary axis PDF

BS31019 – The hypothalamic-pituitary axis Dr Claire Y Hepburn  Learning outcomes Understand the basic structure and anatomy of the hypothalamic-pituitary axis. Contrast the anterior and posterior pituitary with respect to cell types, vascular supply and hypothalamic innervati...

BS31019 – The hypothalamic-pituitary axis Dr Claire Y Hepburn  Learning outcomes Understand the basic structure and anatomy of the hypothalamic-pituitary axis. Contrast the anterior and posterior pituitary with respect to cell types, vascular supply and hypothalamic innervation. Identify the 6 key hormones produced by the anterior pituitary and know their target tissues and functions. Identify two key posterior pituitary hormones and their functions. Understand how specific pituitary tumors alter the physiology and function of the pituitary. Presentation name, Your name, Date  Recommended reading Endocrine and Reproductive Physiology. 4th Edition. Elsevier. Chapter 5 – 99-129 Salhadar, K., et al., (2021). Phosphoproteomic identification of vasopressin/cAMP/protein kinase A-dependent signalling in kidney. Molecular Pharmacology, 99, 358-369. https://doi.org/10.1124/mol.120.119602 Arrowsmith, S., and Wray, S. (2014). Oxytocin: Its mechanism of action and receptor signalling in the myometrium. Journal of Neuroendocrinology, 26, 356-369. https://doi.org/10.1111/jne.12154 BS21002 – Cellular communication – Steroid hormones BS21002 – Cellular communication – Peptide hormones Presentation name, Your name, Date The hypothalamic-pituitary axis The most dominant part of the entire endocrine system. The hypothalamic-pituitary axis (HPA) regulates the function of the thyroid, adrenal and reproductive glands and controls somatic growth, lactation, milk secretion and water metabolism.  Anatomy of the pituitary gland =disease! Adapted from Grey’s Anatomy, 42nd edition, 2021 and AD Instruments, 2022.  Development of the pituitary gland Neurohypophysis = downgrowth of the forebrain Adenohypophysis = oral ectoderm of the roof of stomatodeum Adapted from https://teachmeanatomy.info/the-basics/embryology/head-neck/pituitary-tongue- thyroid/ Cells of the pituitary gland There are different anatomical structures in the adenohypophysis and neurohypophysis that correspond to different function. Adenohypophysis Endocrine tissue with distinct cell types responsible for releasing different hormones Somatotropes Corticotropes Thyrotropes Gonadotropes Lactotropes Neurohypophysis Neural tissue which is responsible for transport and storage of secretory granules of hormones manufactures in the hypothalamus  Vascular supply of the pituitary gland Hypothalam us Hypothalamic Superior hypophyseal neurons artery Hypophyseal portal veins Secondary plexus of the hypophyseal portal system Adenohypophy sis Neurohypophy sis Adapted using Servier Medical Art, provided by Servier, licensed under a Creative Commons Attribution 3.0 unported license  Innervation of the pituitary gland Adapted from Grey’s Anatomy, 42nd edition, 2021.  Neurohypophysis (posterior pituitary) → Supraoptic nuclei = ADH → Paraventricular nuclei = oxytocin Adapted from OpenStax College, CC BY 3.0 , via Wikimedia Commons  Anti-diuretic hormone (ADH) – secretion Secretion is stimulated by Increased plasma osmolality Decrease in blood pressure Stress Pain Adapted from Guyton and Hall Textbook of Medical Physiology, 14 th edition, 2021.  Anti-diuretic hormone (ADH) – physiological effects Increases in ADH secretion increases the permeability of the final 1/3rd of the distal convoluted tubule and the entirety of the collecting duct to water. Increased movement of water from tubular fluid into the interstitial fluid in the kidney leads to increase in plasma volume and blood pressure. This is independent of solute movement. In presence of ADH: Urine flow decreases and urine osmolality increases In absence of ADH: Urine flow increases and urine osmolality decreases Adapted from Guyton and Hall Textbook of Medical Physiology, 14 th edition, 2021.  Anti-diuretic hormone (ADH) – physiological effects cont. Increases in ADH secretion induce vasoconstriction in arterioles Also causes bradycardia and a reduction cardiac output ADH + + PKC PLC Gq/11 + + DA PIP G IP 2 Protein CPI-17 PLC, 3 phospholipase Increased phosphorylation of C; PIP2, + _ + MPMLCMLCK CaM phosphatidyli - nositol Contraction IP3 bisphosphate; Sarcoplasmi receptor DAG, c reticulum diacylglycerol, (SR) PKC, protein Ca2+ Ca2+ kinase C; IP3 – Adapted from Grey’s Anatomy, 42nd edition, 2021. stores inositol trisphosphate;  Anti-diuretic hormone (ADH) – disorders Abnormally high circulating ADH can lead to… High urine osmolality Oedema (due to high plasma volume) Low plasma osmolality Abnormally low circulating ADH can lead to… Diabetes insipidus Adapted from Grey’s Anatomy, 42nd edition, 2021. Oxytocin Stimulates secretion of breast milk from lactating females May also contribution to parturition of a foetus Oxytocin - secretion Secretion of oxytocin is stimulated by… Suckling Vaginal/cervical stimulation during labour Crying  Oxytocin – physiological effects Adapted from Lippincott Illustrated Reviews: Physiology. 2 nd Edition, 2019.  Adenohypophysis (anterior pituitary) Adapted from OpenStax College, CC BY 3.0 , via Wikimedia Commons Adenohypophysis – Hypophysiotropic hormones Hypophysiotropic Primary action at the Acts on Physiological action of Further explanation hormone anterior pituitary anterior pituitary hormones (tropic hormones) Thyrotropin-releasing Stimulates secretion of Thyrotropes Stimulates production of Thyroid hormone and hormone (TRH) thyroid-stimulating hormone thyroid hormones and regulation of resting (TSH) maintains the size of metabolic rate lecture – Dr follicular cells in the thyroid Hormuzdi Gonadotropin-releasing Stimulates secretion of Gonadotropes FSH – Females – stimulates Reproductive endocrinology hormone (GnRH) follicle-stimulating hormone development of ovarian lecture Dr Hormuzdi (FSH) and luteinising follicles. Males – Regulates hormone (LH) spermatogenesis LH – Females - Stimulates ovulation and formation of the corpus luteum. Stimulates production of oestrogen and progesterone in the ovary. Males – Stimulates production of testosterone in the testes. Corticotropin-releasing Stimulates secretion of Corticotropes Stimulates production of The pituitary –adrenal axis hormone (CRH) adrenocorticotropic glucocorticoids and and adrenal glands and hormone (ACTH) androgens in the adrenal adrenal hormones lectures - cortex. Dr Hormuzdi Growth hormone-releasing Stimulates secretion of Somatotropes Stimulates growth of the Hormonal regulation of hormone (GHRH) growth hormone (GH) body. Stimulates secretion growth lecture – Dr Hepburn of insulin-like growth factor. Stimulates lipolysis. Inhibits some actions of insulin. Growth hormone inhibitory Inhibits secretion of growth Somatotropes - Hormonal regulation of  Summary - adenohypophysis hormones Hypophysiotropic hormones via Tropic hypothalamic- hormone hypophysial portal system Parvicellular Adenohypophys is End organ or neuronal cell peripheral bodies in the (anterior endocrine gland hypothalamus pituitary) Adapted from Grey’s Anatomy, 42nd edition, 2021.  Adenohypophysis hormones Thyroid stimulating hormone (TSH) – regulates thyroid function via the TSH receptor on the thyroid epithelial cells. TSH stimulates release of T3 and T4 from the thyroid gland to support tropic effects on growth and metabolism. Adapted from Endocrine and Reproductive Physiology. 4 th Edition, 2013.  Adenohypophysis hormones Follicle stimulating hormone (FSH) and luteinising hormone (LH) - Regulate the function of the gonads in both males and females via the FSH and LH receptors on the gonads. Adapted from Endocrine and Reproductive Physiology. 4 th Edition, 2013.  Adenohypophysis hormones Adrenocorticotropic hormone (ACTH) – Release shows a diurnal pattern and is responsible for stimulating the adrenal cortex to via the MC2R receptor. This induces upregulation of circulating cortisol and adrenal androgen. The released cortisol negatively feeds back to inhibit ACTH secretion in the anterior pituitary Adapted from Endocrine and Reproductive Physiology. 4 th Edition, 2013.  Adenohypophysis hormones Growth hormone (GH) – regulates metabolism via the GH receptor in the liver. The resulting insulin-like growth factor-1 (IGF-1) produced negatively feeds back on production and secretion of GH. This negative feedback is due to the direct effects of IGF- 1 and release of somatostatin from the hypophysiotropic hormone somatostatin. Adapted from Endocrine and Reproductive Physiology. 4 th Edition, 2013. Adenohypophysis hormones Prolactin – stimulates manufacture of breast milk via the reduced release of dopamine from the parvicellular hypothalamic neurons.  A note on these feedback loops in regulation of the HPA A key feature of HPA is the ability of tropic hormones to provide negative feedback upon the system thanks to the hormones they induce release of in their target organs/endocrine glands Feedback can consist of short and long loops… Lon g loop Shor t loop Adapted from Endocrine and Reproductive Physiology. 4 th Edition, 2013.  A note on these feedback loops in regulation of the HPA Gonadotropin-secreting adenomas Rare tumours of the pituitary gland Secrete low quantities of FSH and LH (which can cause clinical symptoms and signs) Generally, symptoms and signs are a function of the sheer size of a tumour Symptoms Headaches Signs Visual field defects Hypopituitarism Adapted from https://geekymedics.com/visual-pathway-and-visual-field-defects/ A note on these feedback loops in regulation of the HPA The most dominant part of the entire endocrine system – plays a pivotal role in influencing hormonal regulation of organs and tissues Pituitary gland differs in embryological origin, and this corresponds to differing anatomical structure and mechanisms for hormone secretion Adenohypophysis is a true endocrine organ Neurohypophysis is neural tissue Adenohypophysis coordinates release of 6 hormones; growth hormone, prolactin, follicle-stimulating hormone, luteinising hormone, thyroid-stimulating hormone and adenocorticotropic hormone Neurohypophysis coordinates the release of antidiuretic hormone and oxytocin Thank you. Questions?