hypothalamus & pituitary felix e. grissom, ph.d. department of physiology & biophysics 2219...
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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