Hypothalamus & pituitary gland Huiping Wang ( 王会平 ), PhD Department of Physiology Rm C541, Block C, Research Building, School of Medicine Tel: 88208292
Outline Hypothalamus Relationship between the hypothalamus and the pituitary Hypothalamic regulatory peptide Pituitary gland Anterior pituitary hormones: 6 Posterior Pituitary Hormones: 2
Relationship between the hypothalamus and the pituitary Hypothalamic pituitary portal system (or hypophyseal portal system) Hypothalamus anterior pituitary Hypothalamohypophyseal p y tract Hypothalamus posterior pituitary
Hypothalamus Hypophysiotrophic area Peptidergic neurons Hypothalamic regulatory peptides» Releasing H» Release-inhibiting H
Hypothalamus Hypothalamic regulatory peptide:9 Thyrotropin-releasing hormone (TRH) Gonadotropin-releasing hormone (GnRH) Corticotropin-releasing hormone (CRH) Growth hormone releasing hormone (GHRH) Prolactin releasing factor (PRF) Growth hormone release-inhibiting hormone (GHRIH; somatostatin, SS) Prolactin release-inhibiting hormone (PIH, DA) Melanophore-stimulating hormone releasing factor (MRF) Melanophore-stimulating hormone release-inhibiting factor (MIF)
Pituitary Gland (Hypophysis) Anterior pituitary(adenohypophysis) Small gland -1 cm diameter, 0.5-1 g originates from epithelium true endocrine tissue secretes 6 classic hormones Posterior pituitary(neurohypophysis) originates i from neural tissue neural tissue (nerve fibers and neuroglial cells) secretes 2 neurohormones Lies in sella turcica and is connected to hypothalamus by hypophyseal stalk Two distinct parts Anterior & Posterior lobes
T t d j f ti f th 6 l i l Targets and major functions of the 6 classical anterior pituitary hormones
For most of the anterior pituitary hormones, the releasing hormones For most of the anterior pituitary hormones, the releasing hormones are important, but for prolactin, PIH (DA) exerts most control
Regulation of hypothalamic and pituitary hormones Typical sequence of events leading from the hypophysiotropic hormone (hormone 1) controls the secretion of hormone 2, which in turn affects the secretion of a hormone by a third endocrine gland (hormone 3). Short loop influence of hypothalamus by an anterior pituitary hormone Long loop inhibition of anterior pituitary and/or hypothalamus by hormone secreted by third endocrine gland
Growth Hormone (GH) Protein (191 aa) Is also named somatotropin, circulating in two forms (22-kDa & 20-kDa) with similar biologic activity Promotes growth of body tissues by increasing the size & numbers of cells Homologous with prolactin and human placenta lactogen (hpl)
Diurnal rhythm GH secretion occurs in episodic bursts and exhibits diurnal rhythm During most of the day, little or no GH is secreted, although bursts can be elicited by certain stimuli such as stress, hypoglycaemia, and exercise In 1 to 2 hours after a person falls asleep, one or larger, prolonged bursts of secretion may occur
Net effect is: GH secretion is highest during adolescence, next highest in children and lower in adults The decreased GH secretion associated with aging is responsible, in part, for the decrease in lean body and bone mass, the expansion of adipose tissue, and the thinning of the skin that occur as people age
Physiologic i functions of GH The most striking and specific effect: growth Most important for postnatal growth Stimulates cartilage and bone growth e.g. promote bone lengthening by stimulating maturation ti and cell division of the chondrocytes in the epiphyseal plate Increase total bone mass and mineral content Stimulates growth of visceral organs Epiphyseal- a part of a long bone where bone growth occurs from
Physiologic functions of GH Studies by Salmon and Daughaday in 1957 demonstrated that GH needs a mediator for its growth-promoting action
Growth Rate in Boys and Girls During pubertal development, GH (either directly or indirectly through IGF-I) collaborates with thyroid hormones, insulin, gonadal hormones and cortisol (permissive effect) to maximize growth potential
Physiologic functions of GH Metabolic Effects of GH Anabolic increase amino acid uptake, protein, RNA/DNA synthesis decrease amino acid/protein degradation Ketogenic increase lipolysis increase fatty acid oxidation ketones Diabetogenic increase plasma glucose ( uptake & gluconeogenesis) Increase insulin secretion
Physiological Functions of Growth Hormone
Information GH supplement for children or adults with normal growth may result in the development of Diabetes Abnormal growth of bones and internal organs (heart, kidneys, and liver) Atherosclerosis Hypertension The American Association of Clinical Endocrinologists has warned that the clinical use of growth hormone as an anti-aging i treatment t t or for patients t with ordinary obesity is not recommended.
Regulation of GH secretion Hypothalamus GHRH and somatostatin t ti (SS) Negative feedback control GH and IGF-I
Factors that Control GH Secretion In addition to the hypothalamus, a number of hormones (sex hormones, insulin and TH) influence the secretion of GH
Abnormalities of GH Secretion Dwarfism Deficiency of GH during childhood A hereditary inability to form IGF-1 Gigantism( pituitary giant ) Over-production of GH by the pituitary gland in a child Excessive long bone growth Usually caused by tumors in the ant. Pituitary gland
Abnormalities of GH Secretion Acromegaly caused by tumors in the ant. Pituitary gland after puberty linear growth is no longer possible excess GH results in thickening of many bones in the body, most noticeably in the hands, feet and head and metabolic derangement
Abnormalities of GH Secretion Acromegaly The jaw enlarges to give the characteristic facial appearance (prognathism)
Abnormalities of GH Secretion Treatment of gigantism and acromegaly usually requires surgical removal of the pituitary tumor Alternatively, treatment with long-acting analogs of somatostatin (inhibits GH secretion) is necessary
Prolactin Protein 207 AA Function
Prolactin Control of secretion Its secretion is tonically inhibited by dopamin (PIH) TRH increases prolactin secretion (hypothyroidism causes galatorrhea)
Posterior Pituitary Hormones Synthesized by cell bodies in hypothalamus (magnocellular neurons) Transported to posterior pituitary in axoplasm of the neuron s fibers Hormones: ADH or vasopressin (supraoptic nuclei) Oxytocin (paraventricular nuclei)
Posterior Pituitary Hormones The similarity of the molecule explains their partial functional similarities.
Actions of Antidiuretic Hormone (ADH) Water retention ti Target organ: ADH-sensitive cells in distal tubules & collecting ducts of renal medulla ADH binds to V 2 receptors Enhances permeability of cell membrane to water Increase vascular tone Target organ: arteriolar smooth muscle cells ADH binds to V 1 receptors Vasoconstriction Therefore ADH is also named Arginine Vasopressin (AVP)
Regulation of ADH secretion osmolality ADH secretion blood volume ADH secretion
Oxytocin (OXT) Secretion Parturition, lactation and coition OXT Action of OXT Contraction of the uterus induces labor contraction ti reduces postpartum bleeding Contraction of myoepithelial cells in the breast stimulates milk let-down
Summary Relationship between the hypothalamus and the pituitary hypophyseal portal system Hypothalamohypophyseal h h l tractt Hypothalamic regulatory peptide:9 Pituitary gland Anterior pituitary hormones:6 GH Physiologic functions of GH» Growth-promoting effect» Metabolic effects Regulation of GH secretion» Hypothalamus:GHRH and SS» Negative feedback control of GH and IGF-I
Summary Pituitary gland anterior pituitary hormones:6 GH Abnormalities of GH Secretion» Dwarfism» Gigantism» Acromegaly Prolactin MSH Posterior Pituitary Hormones:2 ADH OXT