Hypothalamus & Pituitary Felix E. Grissom, Ph.D. Department of Physiology & Biophysics 2219 Adams Building Tel (202) 806-4512

Figure 11-3: Autonomic control centers in the brain

Hypothalamus Integrates functions that maintain chemical and temperature homeostasis Functions with the limbic system Controls the release of hormones from the anterior and posterior pituitary

Hypothalamus Synthesizes releasing hormones in cell bodies of neurons Hormones are transported down the axon and stored in the nerve endings Hormones are released in pulses

Hypothalamic Releasing Hormones Seven releasing hormones are made in the hypothalamus Thyrotropin-releasing hormone (TRH) Corticotropin-releasing hormone (CRH) Gonadotropin-releasing hormone (GnRH) Growth hormone-releasing hormone (GHRH) Growth hormone-release inhibiting hormone (GHIH) Prolactin-releasing factor (PRF) Prolactin-inhibiting hormone (PIH)

Hypothalamus Releasing Hormones: Secretion Is influenced by emotions Can be influenced by the metabolic state of the individual Delivered to the anterior pituitary via the hypothalamic-hypophyseal portal system Usually initiates a three-hormone sequence

Anterior Pituitary Is also called the Adenohypophysis Secretes tropic hormones in a pulsatile fashion Synthesizes various hormones in various specific cell populations

Anterior Pituitary Hormones Each of anterior pituitary hormone is synthesized by a cell population. Corticotropes - ACTH Lactotropes - Prolactin Somatotropes - GH Thyrotropes - Thyrotropin Gonadotropes - FSH, LH

Anterior Pituitary Hormones Growth Hormone (GH, Somatotropin): primary hormone responsible for regulating body growth, and is important in metabolism Thyroid-stimulating Hormone (TSH): stimulates secretion of thyroid hormone & growth of thyroid gland Adrenocorticotropic Hormone (ACTH): stimulates cortisol secretion by the adrenal cortex & promotes growth of adrenal cortex

Anterior Pituitary Hormones Follicle-stimulating Hormone (FSH): Females: stimulates growth & development of ovarian follicles, promotes secretion of estrogen by ovaries. Males: required for sperm production Luteinizing Hormone (LH): Females: responsible for ovulation, formation of corpus luteum in the ovary, and regulation of ovarian secretion of female sex hormones. Males: stimulates cell in the testes to secrete testosterone Prolactin: Females: stimulates breast development and milk production. Males: involved in testicular function

HYPOTHALAMIC HORMONE EFFECTS ON THE ANTERIOR PITUITARY Thyrotropin-releasing hormone (TRH) Stimulates release of TSH (thyrotropin) and Prolactin Corticotropin-releasing hormone (CRH) Stimulates release of ACTH (corticotropin) Gonadrotropin-releasing hormone (GnRH) Stimulates release of FSH and LH (gonadotropins) Growth hormone-releasing hormone (GHRH) Stimulates release of growth hormone Growth hormone-inhibiting hormone (GHIH) Inhibits release of growth hormone {Prolactin-inhibiting hormone (PIH) Stimulates release of prolactin Prolactin-inhibiting hormone (PIH) Inhibits release of prolactin

Growth Hormone Activity Increases plasma free fatty acids (FFA) - source of energy for muscle tissue Increases hepatic glucose output Decreases insulin sensitivity in muscle Is protein anabolic hormone

Growth Hormone Activity Exerts its growth-promoting through interactions [mainly induction of Insulin-like Growth Factor I (IGF-I)]. IGF-I synthesis is stimulated by GH Major source of IGF-I is the liver; IGF-I is also locally produced in other tissues

Endocrine Control: Three Levels of Integration Hypothalamic stimulation–from CNS Pituitary stimulation–from hypothalamic trophic Hs Endocrine gland stimulation–from pituitary trophic Hs

Endocrine Control: Three Levels of Integration Figure 7-13: Hormones of the hypothalamic-anterior pituitary pathway

Multiple Stimuli for Hormone Release: Nervous & Endocrine Stretch Glucose Insulin levels Reflex Lower blood glucose Reduces stimulus Reduces insulin release

Multiple Hormones Can Target a Cell/Tissue Growth Hormone Somatomedins Thyroxin All have receptors on many tissues Stimulate pathways for growth Figure 7-17: A complex endocrine pathway

More Impacts on Target Cells Synergism: multiple stimuli more than additive Cortisol +5 Glucagon +10 Epinephrine +20 (added = +35) Synergistic effect + 140 Antagonism: glucagons opposes insulin Permissiveness: need 2nd hormone to get full expression

More Impacts on Target Cells Figure 7-18: Synergism

Posterior Pituitary Comprised of the endings of axons from cell bodies in the hypothalamus (supraoptic and paraventricular) Axons pass from the hypothalamus to the posterior pituitary via the hypothalamohypophysial tract Posterior pituitary hormones are synthesized in the cell bodies of neurons in the supraoptic and paraventricular nuclei

Posterior Pituitary Hormones synthesized in the hypothalamus are transported down the axons to the endings in the posterior pituitary Hormones are stored in vesicles in the posterior pituitary until release into the circulation Principal Hormones: Vasopressin & Oxytocin

Secretion of Posterior Pituitary Hormones Figure 7-12: Synthesis, storage, and release of posterior pituitary hormones

Oxytocin Is synthesized as the precursor hormone: prepro-oxyphysin Acts primarily on the mammary gland and uterus Increases contraction of smooth muscle of the vas deferens

Oxytocin Secretion is increased during labor May also act to facilitate sperm transport in uterus (non-pregnancy state)

Posterior Pituitary: Regulation of Osmolality Plasma osmolality is monitored by osmoreceptors in the hypothalamus Increases in plasma osmolality stimulates secretion of vasopressin Small changes above the normal plasma osmotic pressure (285 mosm/kg) stimulate release of vasopressin

Vasopressin (ADH) Is also known as antiduretic hormone (ADH) Participates in body water regulation (Water is lost from lungs, sweat, feces and urine on a daily basis)

Loss or gain of water without solutes (free water Osmolality Refers to the amount of solutes in a solution Loss or gain of water without solutes (free water gain or loss) changes the osmolality of ECF Must be regulated to maintain normal cell activity

Vasopressin (ADH) Secretion Secretion is Stimulated by: 1. Large decreases in blood volume 2. Decreases in blood pressure 3. Pain, fear, trauma, and stress

Vasopressin Activity Decreases water excretion by kidneys (V2 receptors) Constricts blood vessels (V1 receptors)- arteriolar smooth muscle Increases adrenocorticortropin hormone (V1B receptors) secretion from the anterior pituitary

Negative Feedback Controls: Long & Short Loop Reflexes Figure 7-14: Negative feedback loops in the hypothalamic-anterior pituitary pathway

Negative Feedback Controls: Long & Short Loop Reflexes Figure 7-15: Control pathway for cortisol secretion

Pathologies: Over or Under Production "no bad hormones – just too much or too little" Exogenous medication Replaces & exceeds normal Cause atrophy of gland Hypersecretion: too much Tumors or cancer Grave's disease- thyroxin Hyposecretion: too little Goiter – thyroxin Diabetes – insulin

Pathologies: Over or Under Production Figure 7-19: Negative feedback by exogenous cortisol

Pathologies: Due to Receptors Downregulation – hyperinsulinemia Transduction abnormalities Testicular feminization syndrome Pseudohypothyroidism Abnormalities of control mechanisms

Pathologies: Due to Receptors Figure 7-20: Primary and secondary hypersecretion of cortisol