Endocrine System III Lecture Notes PDF

ENDOCRINE SYSTEM III Hypothalamus – Pituitary axis (Integration of Hormone Action) ANSC 3080 G. Bedecarrats  Learning Objectives  Illustrate the position of the hypothalamus and pituitary gland  Outline the integration of hormonal systems with the hypothalamus  Describe...

ENDOCRINE SYSTEM III Hypothalamus – Pituitary axis (Integration of Hormone Action) ANSC 3080 G. Bedecarrats  Learning Objectives  Illustrate the position of the hypothalamus and pituitary gland  Outline the integration of hormonal systems with the hypothalamus  Describe the integration of hypothalamic and pituitary function (nervous/pituitary- hypothalamic portal system)  Describe the nature of the hypothalamic releasing and inhibiting hormones  Describe the hormones produced by the anterior and posterior pituitary gland  Brain, Hypothalamus, Pituitary Back Top Front cerebrum Hypothalamus Cerebellum Stalk Posterior pituitary Anterior Sphenoid bone pituitary Bottom  Hypothalamo-Pituitary Axis  Hypothalamus is the major integration center  It is part of the brain  Regulates the autonomic nervous system  Regulates most of the endocrine system  Processes most sensory information  The pituitary is a small gland attached to the hypothalamus  Three parts: posterior, intermediate and anterior  Posterior lobe = neurons from hypothalamus  Anterior lobe = major endocrine part (glandular tissue)  Intermediate = major function in amphibians and fish (MSH).  Anterior lobe and intermediate often considered as anterior pituitary Hypothalamo-Pituitary Axis Hypothalamus composed of neuroendocrine cells  Some project axons down the posterior pituitary lobe  Some release factors into the pituitary stalk portal venous system to feed the anterior pituitary Endocrine cells from the anterior and intermediate pituitary release their hormones in a second capillary network  enter systemic circulation  Intermediate Pituitary Role in mammals? Source of -endorphins? Produces:  MSH = melanocyte stimulating hormone   skin pigment  -LPH (-lipotropin): degraded to -endorphin = analgesia during stress  All derived from the common gene POMC (pro- opiomelanocortin)  Posterior (nervous) Pituitary  Releases antidiuretic hormone (ADH or vasopressin) and oxytocin produced in the cell body of hypothalamic neurons  Transported to the pituitary along axons in vesicles  Stored in nerve endings, released when AP is fired  After secretion, hormones diffuse into blood vessels  Plasma half-life: 3-5 min Tyr Cys Tyr Cys Ile S Phe S Gln S Gln S Asn Cys Pro Leu Gly NH2 Asn Cys Pro Arg Gly NH2 Oxytocin Vasopressin Anti Diuretic Hormone  Most important regulator of extracellular fluid  Acts in the kidneys: regulates the density of aquaporins (water channels) in the distal tubule and collecting duct  ADH  reabsorption of water  Primarily regulated by hypothalamic osmoreceptors and stretch receptors in blood vessels  Oxytocin  Primarily acts on Uterus smooth muscle: contraction during parturition Mammary gland: contraction  pressure to drive milk towards excretory ducts and the teats (milk ejection reflex)  Receptor = G-coupled receptor with activation of PLC (Ca pathway)  Secretion of oxytocin regulated by several reflexes Milk Ejection Reflex  Anterior Pituitary (Master Gland)  Endocrine part: contains 5 different cell types producing 6 different hormones  Proteins or glycoproteins with longer half-lives than their releasing hormones TSH (thyroid stimulating hormone)  thyrotrope LH & FSH (gonadotropins)  gonadotrope ACTH (adrenocorticotropin)  corticotrope GH (growth hormone)  somatotrope PRL (prolactin)  mammotrope (lactotrope)  Tropic effects = regulate other endocrine glands  Under direct control (positive and/or negative) from hypothalamus  Function of Anterior Pituitary Hormones:  GH (somatotropin): cytokine receptor type Direct effects: stimulates lipolysis and reduces lipogenesis in adipose tissue (catabolic); promotes synthesis of protein (anabolic) Indirect effects: by stimulating synthesis of IGF1(somatomedin) and its binding proteins in the liver. Stimulates chondrocyte (cartilage cells) proliferation to increase bone growth; stimulates satellite cells in muscle (muscle fibre growth); stimulates amino acid uptake and protein synthesis  TSH (thyrotropic hormone): TSH binds to its G-coupled receptor on membrane of follicular cells in thyroid gland, stimulates cAMP pathway which in turn stimulates the synthesis of thyroid hormones (will be described in more details)  ACTH (adrenocorticotropic hormone) ACTH receptor is a G-coupled receptor stimulating the cAMP pathway Stimulates the mobilisation of cholesterol in adrenal cortex = more substrate for cytochrome P-450  increases release of corticosteroids LH: G-protein coupled receptor (cAMP pathway)  In male: stimulates testosterone production by Leydig cells in the testis  In female: controls sex steroid production by the ovary and is responsible for ovulation (surge) FSH: G-protein coupled receptor (cAMP pathway)  In male: stimulates secretion of inhibin by Sertoli cells  In female: development of follicles and secretion of sex steroids PRL (prolactin): cytokine receptor type  Stimulates the synthesis of milk proteins (casein, lactalbumin)  In poultry, responsible for the initiation and maintenance of incubation behaviour (broodiness)  Hypothalamic Control of Anterior Pituitary  Neurohormones released in small amount (bypass general circulation)  Hypothalamic neurons receive information from: Higher brain center, emotions Exterior, environmental and social stimuli Internal rhythms Metabolic state (temperature, energy level, osmolarity) Endogenous hormones by feedback  Hypothalamus GnRH GnIH ACTH-RH TRH GH-RH GH-IH Dopamine Birds VIP - - + + + + + + - -  Some hormones are under tonic inhibition (GH, MSH, PRL). These hormones are needed early in life. As the hypothalamus matures and animal ages, secretion   Species differences: in mammals PRL is mainly under dopaminergic tonic inhibition, in birds it is mainly under VIP stimulation  Each anterior pituitary hormone has a corresponding hypothalamic releasing hormone and/or a corresponding hypothalamic inhibitory factor  Hypothalamic factors are all relatively small peptides generally fragments from proprotein of larger size  Different releasing hormones synthesized by specific neurons  Releasing hormone precursors are made in cell bodies and transported down the axons to the nerve endings for storage  Electrical stimulus = released by hypothalamus delivered to pituitary by portal system release of hormone by pituitary release of ultimate hormone in target gland. Amplification of signal at each step. Environmental or CNS internal signal Electrical/chemical signal Limbic system Electrical/chemical signal Hypothalamus Releasing factorsng) ( Anterior pituitary Anterior pituitary hormone (µg) Target “gland” Ultimate hormone (mg) Systemic effects Hormonal cascade of signals from CNS to ultimate hormone Pulsatility  Many hormones from the hypothalamus and pituitary are pulsatile or episodic  Regulated by the biological clock of hypothalamic suprachiasmatic nucleus  May prevent the down regulation of receptors from continuous level of hormone secretion  Can trigger specific action depending on pulse frequency  Feedback Control  Circulating hormones from the endocrine glands provide negative feedback both to the hypothalamus and pituitary  Feedback serves to regulate the secretion of hormones  Two major feedback loops: Short loop: pituitary hormones feed back to hypothalamus Long loop: hormones from target glands feed back to the pituitary and hypothalamus