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

• Hypothalamic stimulation–from CNS • Pituitary stimulation–from hypothalamic trophic Hs• Endocrine gland stimulation–from pituitary trophic Hs

Endocrine Control: Three Levels of Integration

Endocrine Control: Three Levels of Integration

Figure 7-13: Hormones of the hypothalamic-anterior pituitary pathway

• Stimuli– Stretch– Glucose– Insulin levels

• Reflex– Lower blood glucose– Reduces stimulus– Reduces insulin release

Multiple Stimuli for Hormone Release:

Nervous & Endocrine

• Growth Hormone

• Somatomedins

• Thyroxin– All have receptors

on many tissues– Stimulate pathways

for growth

Multiple Hormones Can Target a Cell/Tissue

Figure 7-17: A complex endocrine pathway

• 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

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)

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

• "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

Pathologies: Over or Under Production

Figure 7-19: Negative feedback by exogenous cortisol

• Downregulation – hyperinsulinemia

• Transduction abnormalities– Testicular feminization syndrome– Pseudohypothyroidism

• Abnormalities of control mechanisms

Pathologies: Due to Receptors

Pathologies: Due to Receptors

Figure 7-20: Primary and secondary hypersecretion of cortisol