Endocrine Cells of the Hypothalamohypopyseal Axis the Portal

Endocrine Cells of the Hypothalamohypopyseal Axis & the Portal Circulation Third ventricle Hypothalamus Median eminence Superior hypophyseal artery Stalk Long portal Adenohypophysis vessels Neurohypophysis Hormone secreting cell Hormone Vein Inferior hypophyseal artery Copyright © 2006 by Elsevier, Inc. Short portal vessels Vein

Adenohypophyseal Cells & Hormones Cell Hormone Chemistry Physiologic Actions Adrenocorticotropic hormone (corticotropin; ACTH) Single chain of 39 amino acids Stimulates production of glucocorticoids androgens by the adrenal cortex; maintains size of zona fasciculata and zona reticularis of cortex Thyroid-stimulating hormone (thyrotropin; TSH) Glycoprotein having two subunits, (89 amino acids) and ß (112 amino acids) Stimulates production of thyroid hormones, T 4 and T 3, by thyroid follicular cells; maintains size of follicular cells Gonadotropes Follicle-stimulating hormone (FSH) Glycoprotein having two sub- Stimulates development of ovarian follicles; units, (89 aa) and ß (115 aa) regulates spermatogenesis in the testis Gonadotropes Lutenizing hormone (LH) Corticotropes Thyrotropes Mammotropes, Prolactin (PRL) Lactotropes Somatotropes Growth hormone (somatotropin; GH) Copyright © 2006 by Elsevier, Inc. Glycoprotein having two sub- Causes ovulation and formation of corpus luteum units, (89 aa) and ß (115 aa) in the ovary; stimulates production of estrogen and progesterone by the ovary; stimulates testosterone production by the testis Single chain of 198 amino acids Essential for milk production by lactating mammary gland Single chain of 191 amino acids Stimulates postnatal body growth; stimulates secretion of IGF-1; stimulates triglyceride lipolysis; inhibits actions of insulin on carbohydrate and lipid metabolism

Hypophysiotropic Hormones Hormone Predominant hypothalamic localization Structure Actions on Anterior Pituitary Thyrotropin-releasing hormone (TRH) Paraventricular Peptide consisting of Stimulates secretion of TSH by 3 amino acids thyrotropes; stimulates expression of genes for and ß subunits of TSH thyrotropes; stimulates synthesis of PRL by lactotropes Gonadotropin-releasing hormone (Gn. RH) Arcuate Single chain of 10 amino acids Stimulates secretion of FSH and LH by gonadotropes Corticotropin-releasing hormone (CRH) Paraventricular Single chain of 41 amino acids Stimulates secretion of ACTH by corticotropes; stimulates expression of gene for POMC in corticotropes Growth hormone-releasing hormone (GHRH) Arcuate Single chain of 44 amino acids Stimulates secretion of GH by somatotropes; stimulates expression of gene for GH in somatotropes Single chain of 14 amino acids Inhibits secretion of GH by somatotropes Dopamine Inhibits biosynthesis and secretion of PRL by lactotropes Growth hormone-inhibiting Anterior hormone (somatostatin) periventricular Prolactin-inhibiting hormone (PIH) Copyright © 2006 by Elsevier, Inc. Arcuate

Hypothalamohypophyseal – Target Gland Axis _ Hypothalamus + Releasing hormones Inhibiting Hormones _ + _ Anterior Pituitary Tropic Hormone + Target Gland Hormone Copyright © 2006 by Elsevier, Inc.

Metabolic Effects of Growth Hormone Glycogen Protein Glucose-P Amino acids Glucose Free fatty acids Pyruvate Liver Ketoacids Muscle Plasma Copyright © 2006 by Elsevier, Inc. Stimulate Inhibit Glucose Free fatty acids Ketoacids Amino acids Adipose tissue

IGF-I (Somatomedin C) • • • Circulating IGF-I produced in liver in response to GH Stimulates chondrocytes → ↑ linear growth Structure & receptors ~ to those of insulin Inhibits GH secretion Highly bound to plasma proteins-- T 1/2: IGF-I > GH Copyright © 2006 by Elsevier, Inc.

Hypothalamohypophyseal-GH Axis _ Hypothalamus + GHRH Somatostatin _ + _ Somatotrope Growth hormone + Liver IGF-I Copyright © 2006 by Elsevier, Inc.

Factors Affecting Growth Hormone Secretion Stimulation Glucose decrease Free fatty acid decrease Fasting Prolonged caloric deprivation Amino acid increase (arginine) Stress Exercise Puberty Androgens and estrogens Sleep Copyright © 2006 by Elsevier, Inc. Inhibition Somatostatin Glucose increase Free fatty acid increase Somatomedins Growth hormone Cortisol Senescence

Pathophysiology of Growth Hormone • Gigantism • Acromegaly • Dwarfism Copyright © 2006 by Elsevier, Inc.

Copyright © 2006 by Elsevier, Inc.