Faisal I. Mohammed, MD, PhD Endocrine System L3 Faisal I. Mohammed, MD, PhD University of Jordan

Hypothalamus and Pituitary Gland

Anterior pituitary Release of hormones stimulated by releasing and inhibiting hormones from the hypothalamus Also regulated by negative feedback Hypothalamic hormones made by neurosecretory cells transported by hypophyseal portal system Anterior pituitary hormones that act on other endocrine systems called tropic hormones University of Jordan

Hormones of the Anterior Pituitary Human growth hormone (hGH) or somatotropin Stimulates secretion of insulin-like growth factors (IGFs) that promote growth, protein synthesis Thyroid-stimulating hormone (TSH) or thyrotropin Stimulates synthesis and secretion of thyroid hormones by thyroid Follicle-stimulating hormone (FSH) Ovaries initiates development of oocytes, testes stimulates testosterone production Luteinizing hormone (LH) Ovaries stimulates ovulation, testes stimulates testosterone production University of Jordan

Hormones of the Anterior Pituitary Prolactin (PRL) Promotes milk secretion by mammary glands Adrenocorticotropic hormone (ACTH) or corticotropin Stimulates glucocorticoid secretion by adrenal cortex Melanocyte-stimulating Hormone (MSH) Unknown role in humans University of Jordan

Negative Feedback Regulation University of Jordan

Hypothalamic Control of the Anterior Pituitary Hormonal control rather than neural. Hypothalamus neurons synthesize releasing and inhibiting hormones. Hormones are transported to axon endings of median eminence. Hormones secreted into the hypothalamo-hypophyseal portal system regulate the secretions of the anterior pituitary University of Jordan

Feedback Control of the Anterior Pituitary Anterior pituitary and hypothalamic secretions are controlled by the target organs they regulate. Secretions are controlled by negative feedback inhibition by target gland hormones. Negative feedback at 2 levels: The target gland hormone can act on the hypothalamus and inhibit secretion of releasing hormones. The target gland hormone can act on the anterior pituitary and inhibit response to the releasing hormone. University of Jordan

Feedback Control of the Anterior Pituitary (continued) Short feedback loop: Retrograde transport of blood from anterior pituitary to the hypothalamus. Hormone released by anterior pituitary inhibits secretion of releasing hormone. Positive feedback effect: During the menstrual cycle, estrogen stimulates “LH surge.” University of Jordan

Higher Brain Function and Pituitary Secretion Axis: Relationship between anterior pituitary and a particular target gland. Pituitary-gonad axis. Hypothalamus receives input from higher brain centers. Psychological stress affects: Circadian rhythms. Menstrual cycle. University of Jordan

Effects of hGH and IGFs High levels of GH before puberty causes Gigantism, after puberty causes Acromegaly. Low levels of GH before puberty causes Dwarfism, after puberty leads to some Metabolic effects University of Jordan

Pituitary Hormones Anterior Pituitary: Trophic effects: High blood [hormone] causes target organ to hypertrophy. Low blood [hormone] causes target organ to atrophy. University of Jordan

Posterior pituitary Does not synthesize hormones Stores and releases hormones made by the hypothalamus Transported along hypothalamohypophyseal tract Oxytocin (OT) Antidiuretic hormone (ADH) or vasopressin University of Jordan

Posterior Pituitary Hormones Stores and releases 2 hormones that are produced in the hypothalamus: Antidiuretic hormone (ADH/vasopressin): Promotes the retention of H20 by the kidneys. Less H20 is excreted in the urine. Oxytocin: Stimulates contractions of the uterus during parturition. Stimulates contractions of the mammary gland alveoli. Milk-ejection reflex. University of Jordan

Hypothalamohypophyseal tract University of Jordan

Hypothalamic Control of Posterior Pituitary Hypothalamus neuron cell bodies produce: ADH: supraoptic nuclei. Oxytocin: paraventricular nuclei. Transported along the hypothalamo-hypophyseal tract. Stored in posterior pituitary. Release controlled by neuroendocrine reflexes. University of Jordan

Oxytocin (OT) During and after delivery of baby affects uterus and breasts Enhances smooth muscle contraction in wall of uterus Stimulates milk ejection from mammary glands University of Jordan

Antidiuretic Hormone (ADH) Decreases urine production by causing the kindeys to return more water to the blood Also decreases water lost through sweating and constriction of arterioles which increases blood pressure (vasopressin) University of Jordan

Osmoreceptors High blood osmotic pressure stimulates hypothalamic osmoreceptors Low blood osmotic pressure inhibits Nerve impulses liberate ADH from axon terminals in the posterior pituitary into the bloodstream activate the neurosecretory cells that synthesize and release ADH Hypothalamus Sudoriferous (sweat) glands decrease water loss by perspiration from the skin Arterioles constrict, which increases blood pressure Kidneys retain more water, which decreases urine output ADH Target tissues 1 2 3 4 5 Osmoreceptors High blood osmotic pressure stimulates hypothalamic osmoreceptors Low blood osmotic pressure inhibits Nerve impulses liberate ADH from axon terminals in the posterior pituitary into the bloodstream activate the neurosecretory cells that synthesize and release ADH Hypothalamus Inhibition of osmo- receptors reduces or stops ADH secretion Sudoriferous (sweat) glands decrease water loss by perspiration from the skin Arterioles constrict, which increases blood pressure Kidneys retain more water, which decreases urine output ADH Target tissues 1 2 3 4 5 6 Osmoreceptors High blood osmotic pressure stimulates hypothalamic osmoreceptors Nerve impulses liberate ADH from axon terminals in the posterior pituitary into the bloodstream activate the neurosecretory cells that synthesize and release ADH Hypothalamus Sudoriferous (sweat) glands decrease water loss by perspiration from the skin Arterioles constrict, which increases blood pressure Kidneys retain more water, which decreases urine output ADH Target tissues 1 2 3 4 Osmoreceptors High blood osmotic pressure stimulates hypothalamic osmoreceptors Nerve impulses liberate ADH from axon terminals in the posterior pituitary into the bloodstream activate the neurosecretory cells that synthesize and release ADH Hypothalamus ADH 1 2 3 Osmoreceptors High blood osmotic pressure stimulates hypothalamic osmoreceptors 1 Osmoreceptors High blood osmotic pressure stimulates hypothalamic osmoreceptors activate the neurosecretory cells that synthesize and release ADH Hypothalamus 1 2 University of Jordan

Thyroid Gland Located inferior to larynx 2 lobes connected by isthmus Thyroid follicles produce thyroid hormones Thyroxine or tetraiodothyronine (T4) Triiodothyronine (T3) Both increase BMR, stimulate protein synthesis, increase use of glucose and fatty acids for ATP production Parafollicular cells or C cells produce calcitonin Lowers blood Ca2+ by inhibiting bone resorption University of Jordan

Thyroid Gland University of Jordan

Thyroid Hormones Thyroid gland is located just below the larynx. Thyroid is the largest of the pure endocrine glands. Follicular cells secrete thyroxine. Parafollicular cells secrete calcitonin. University of Jordan

Production of Thyroid Hormones Iodide (I-) actively transported into the follicle and secreted into the colloid. Oxidized to iodine (Io). Iodine attached to tyrosine within thyroglobulin chain. Attachment of 1 iodine produces monoiodotyrosine (MIT). Attachment of 2 iodines produces diiodotyrosine (DIT). MIT and DIT or 2 DIT molecules coupled together. University of Jordan

Production of Thyroid Hormones (continued) T3 and T4 produced. TSH stimulates pinocytosis into the follicular cell. Enzymes hydrolyze T3 and T4 from thyroglobulin. Attached to TBG and released into blood. University of Jordan

Production of Thyroid Hormones (continued) University of Jordan

Actions of T3 Stimulates protein synthesis. Promotes maturation of nervous system. Stimulates rate of cellular respiration by: Production of uncoupling proteins. Increase active transport by Na+/K+ pumps. Lower cellular [ATP]. Increases metabolic heat. Increases metabolic rate. Stimulates increased consumption of glucose, fatty acids and other molecules. University of Jordan

Diseases of the Thyroid Iodine-deficiency (endemic) goiter: Abnormal growth of the thyroid gland. In the absence of sufficient iodine, cannot produce adequate amounts of T4 and T3. Lack of negative feedback inhibition. Stimulates TSH, which causes abnormal growth. University of Jordan

Control of thyroid hormone secretion Thyrotropin-releasing hormone (TRH) from hypothalamus Thyroid-stimulating hormone (TSH) from anterior pituitary Situations that increase ATP demand also increase secretion of thyroid hormones University of Jordan

Mechanism of Thyroid Hormone Action T4 passes into cytoplasm and is converted to T3. Receptor proteins located in nucleus. T3 binds to ligand-binding domain. Other half-site is vitamin A derivative (9-cis-retinoic) acid. DNA-binding domain can then bind to the half-site of the HRE. Two partners can bind to the DNA to activate HRE. Stimulate transcription of genes. University of Jordan

Synthesis of thyroid hormones University of Jordan

1 2 3 4 1 2 3 5 4 1 2 3 1 2 1 T3 and T4 released into blood by follicular cells TRH, carried by hypophyseal portal veins to anterior pituitary, stimulates release of TSH by thyrotrophs TSH released into blood stimulates thyroid follicular cells Thyroid follicle Low blood levels of T3 and T3 or low metabolic rate stimulate release of Hypothalamus Anterior pituitary TSH TRH Actions of Thyroid Hormones: Increase basal metabolic rate Stimulate synthesis of Na+/K+ ATPase Increase body temperature (calorigenic effect) Stimulate protein synthesis Increase the use of glucose and fatty acids for ATP production Stimulate lipolysis Enhance some actions of catecholamines Regulate development and growth of nervous tissue and bones 1 2 3 4 T3 and T4 released into blood by follicular cells Elevated T3inhibits release of TRH and TSH (negative feedback) TRH, carried by hypophyseal portal veins to anterior pituitary, stimulates release of TSH by thyrotrophs TSH released into blood stimulates thyroid follicular cells Thyroid follicle Low blood levels of T3 and T3 or low metabolic rate stimulate release of Hypothalamus Anterior pituitary TRH Actions of Thyroid Hormones: Increase basal metabolic rate Stimulate synthesis of Na+/K+ ATPase Increase body temperature (calorigenic effect) Stimulate protein synthesis Increase the use of glucose and fatty acids for ATP production Stimulate lipolysis Enhance some actions of catecholamines Regulate development and growth of nervous tissue and bones 1 2 3 5 4 TRH, carried by hypophyseal portal veins to anterior pituitary, stimulates release of TSH by thyrotrophs TSH released into blood stimulates thyroid follicular cells Thyroid follicle Low blood levels of T3 and T3 or low metabolic rate stimulate release of Hypothalamus Anterior pituitary TSH TRH Actions of Thyroid Hormones: Increase basal metabolic rate Stimulate synthesis of Na+/K+ ATPase Increase body temperature (calorigenic effect) Stimulate protein synthesis Increase the use of glucose and fatty acids for ATP production Stimulate lipolysis Enhance some actions of catecholamines Regulate development and growth of nervous tissue and bones 1 2 3 TRH, carried by hypophyseal portal veins to anterior pituitary, stimulates release of TSH by thyrotrophs Low blood levels of T3 and T3 or low metabolic rate stimulate release of Hypothalamus TSH TRH Actions of Thyroid Hormones: Increase basal metabolic rate Stimulate synthesis of Na+/K+ ATPase Increase body temperature (calorigenic effect) Stimulate protein synthesis Increase the use of glucose and fatty acids for ATP production Stimulate lipolysis Enhance some actions of catecholamines Regulate development and growth of nervous tissue and bones 1 2 Anterior pituitary Low blood levels of T3 and T3 or low metabolic rate stimulate release of Hypothalamus TRH Actions of Thyroid Hormones: Increase basal metabolic rate Stimulate synthesis of Na+/K+ ATPase Increase body temperature (calorigenic effect) Stimulate protein synthesis Increase the use of glucose and fatty acids for ATP production Stimulate lipolysis Enhance some actions of catecholamines Regulate development and growth of nervous tissue and bones 1 Anterior pituitary University of Jordan

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