Hypothalamic-Pituitary Relationships PDF

HYPOTHALAMIC- PITUITARY RELATIONSHIPS 407-419 sergeenko PITUITARY GLAND AND ITS RELATION TO THE HYPOTHALAMUS THE ANTERIOR AND POSTERIOR LOBES OF THE PITUITARY GLAND The pituitary gland, also called the hypophysis is connected to the hypothalamus by the pituitary (or hypophysia...

HYPOTHALAMIC- PITUITARY RELATIONSHIPS 407-419 sergeenko PITUITARY GLAND AND ITS RELATION TO THE HYPOTHALAMUS THE ANTERIOR AND POSTERIOR LOBES OF THE PITUITARY GLAND The pituitary gland, also called the hypophysis is connected to the hypothalamus by the pituitary (or hypophysial) stalk.infundibulum. it has two main distinct portions: the anterior pituitary, also known as the adenohypophysis, and the posterior pituitary, also known as the neurohypophysis. Between these portions is a small, relatively avascular zone called the pars intermedia. important peptide hormones are secreted by the two posterior pituitary-oxytocin and vasopressin[ADH], Posterior Pituitary Hormones Are Synthesized by Cell Bodies in the Hypothalamus and then transported in the axoplasm of the neurons’ nerve fibers passing from the hypothalamus to the posterior pituitary gland. anterior lobe is primarily a collection of endocrine cells. The anterior pituitary secretes six peptide hormones: thyroid-stimulating hormone (TSH), FSH, LH, growth hormone, prolactin, and adrenocorticotropic hormone (ACTH. Relationship of the Hypothalamus to the Anterior Pituitary The hypothalamus and anterior pituitary are linked directly by the hypothalamic-hypophysial portal blood vessels, which provide most of the blood supply of the anterior lobe. (1) The hypothalamic hormones can be delivered to the anterior pituitary directly and in hig concentration, and (2) the hypothalamic hormones do not appear in the systemic circulation in high concentrations.  blood supply There are both long and short hypophysial portal vessels, which are distinguished as follows: Arterial blood is delivered to the hypothalamus via the superior hypophysial arteries, which distribute the blood in a capillary network in the median eminence, called the primary capillary plexuses. These primary capillary plexuses converge to form the long hypophysial portal vessels, which travel down the infundibulum to deliver hypothalamic venous blood to the anterior lobe of the pituitary. A parallel capillary plexus forms from the inferior hypophysial arteries in the lower portion of the infundibular stem. These capillaries converge to form the short hypophysial portal vessels, which deliver blood to the anterior lobe of the pituitary.  V.anterior lobe is primarily a collection of endocrine cells. The anterior pituitary secretes six peptide hormones: (TSH), FSH, LH, growth hormone, prolactin, and adrenocorticotropic hormone (ACTH. TSH is secrete by thyrotrophs (5%), FSH and LH by gonadotrophs (15%), ACTH by corticotrophs (15%), growth hormone by somatotrophs (20%), and prolactin by lactotrophs (15%) The hormone is stored in membrane-bound secretory granules for subsequent release. When the anterior pituitary is stimulated by a hypothalamic-releasing hormone or a release-inhibiting hormone.. The hormones of the anterior lobe are organized in “families” according to their structural and functional homology. 1. TSH, FSH, and LH are structurally related and constitute one family,The α subunits of TSH, FSH, and LH are identical and are synthesized from the same mRNA. The β subunits foreach hormone are different,, The placental hormone human chorionic gonadotropin (HCG) is structurally related to the TSH-FSH-LH family. Thus HCG is a glycoprotein with the identical α chain and its own β chain, which confers its biologic specificity 2.ACTH is part of a 2nd family, and 3.growth hormone and prolactin constitute a 3rd family  ACTH Family The ACTH family is derived from a single precursor, pro-opiomelanocortin (POMC). The ACTH family includes ACTH, γ- and β-lipotropin, β-endorphin, and melanocyte- stimulating hormone (MSH. humans. β-Endorphin is an endogenous opiate. The preprohormone for this group, pre-POMC, is transcribed from a single gene. The signal peptide is cleaved in the endoplasmic reticulum, yielding POMC, the precursor to the ACTH family. Endopeptidases then hydrolyze peptide bonds in POMC and intermediates to produce the members of the ACTH family (Fig. 9.10). The anterior pituitary in humans produces mainly ACTH, γ-lipotropin, and β-endorphin. It is noteworthy that MSH activity is found in POMC and in several of its products: The “fragment,” which is left over from hydrolysis of the ACTH intermediate, contains γ- MSH; These MSH-containing fragments can cause skin pigmentation in humans if their blood levels are increased. For example, in Addison disease (primary adrenal insufficiency), POMC and ACTH levels are increased by negative feedback. Because POMC and ACTH contain MSH activity, skin pigmentation is a symptom of this disorder Growth Hormone Chemistry of Growth Hormone Growth hormone is synthesized in the somatotrophs of the anterior lobe of the pituitary and also is called somatotropin or somatotropic hormone. Regulation of Growth Hormone Secretion Growth hormone is secreted in a pulsatile pattern, with bursts of secretion occurring approximately every 2 hours. The largest secretory burst occurs within 1 hour of falling asleep (during sleep stages III and IV. Growth hormone secretory rates are not constant over a lifetime. s During childhood, The rate of secretion remains relatively stable. At puberty, there is an enormous secretory burst, induced in females by estrogen and in males by testosterone. The high pubertal levels of growth hormone are associated with both increased frequency and increased magnitude of the secretory pulses and are responsible for the growth spurt of puberty The major factors that alter growth hormone secretion are summarized in Table 9.4. Hypoglycemiaand starvation are potent stimuli for growth hormone secretion. Other stimuli for secretion are exercise and stress including trauma, fever, and anesthesia. Secretion of growth hormone by the anterior pituitary is controlled by two pathways from the hypothalamus, 1.stimulatory (GHRH) 2.inhibitory (somatostatin, also known as somatotropin release– inhibiting factor [SRIF]).. ♦ GHRH acts directly on somatotrophs of the anterior pituitary to induce transcription of the growth hormone gene. Thus GHRH stimulates growth hormone secretion by utilizing both cAMP and IP3/Ca2+ as second messengers. ♦Somatostatin (somatotropin release–inhibiting hormone [SRIF])inhibits growth hormone secretion by blocking the action of GHRH on the somatotroph. Somatostatin binds to its own membrane receptor, which is coupled to adenylyl cyclase by a Gi protein, inhibiting the generation of cAMP and decreasing growth hormone secretion Growth hormone secretion is regulated by negative feedback (see Fig. 9.11). Three feedback loops including both long and short loops are involved. (1) GHRH inhibits its own secretion from the hypothalamus via an ultrashort-loop feedback. (2) Somatomedins, which are byproducts of the growth hormone action on target tissues, inhibit secretion of growth hormone by the anterior pituitary. (3) Both growth hormone and somatomedins stimulate the secretion of somatostatin by the hypothalamus. The overall effect of this third loop is inhibitory (i.e., negative feedback) because somatostatin inhibits growth hormone secretion by the anterior pituitary Actions of Growth Hormone 1.Some of the actions of growth hormone result from the hormone’s direct effect on target tissues such as skeletal muscle, the liver, or adipose tissue. These direct actions are mediated by tyrosine kinase– associated receptors. 2.Other actions of growth hormone are mediated indirectly through the production of somatomedins (or IGFs) in the liver. The most important of the somatomedins is somatomedin C or IGF-1. Somatomedins act on target tissues through IGF receptors that are similar to the insulin receptor, having intrinsic tyrosine kinase activity and exhibiting autophosphorilation. ♦ Diabetogenic or anti-insulin effect. growth hormone– induced “insulin resistance,” which attenuates insulin’s actions to stimulate uptake and utilization of glucose in skeletal muscle and adipose tissue and to inhibit gluconeogenesis (glucose production) by the liver. For these reasons, growth hormone’s effects are called diabetogenic because it can produce metabolic disturbances similar to those found in patients with type II (non–insulin- dependent) diabetes, who are also resistant to the metabolic effects of insulin. ♦ Increased protein synthesis and organ growth. In virtually all organs, growth hormone increases the uptake of amino acids and stimulates the synthesis of DNA, RNA, and protein ♦ Increased linear growth. The most striking effect of growth hormone is its ability to increase linear growth Pathophysiology of growth hormone (1) Growth hormone deficiency in children causes failure to grow, short stature, mild obesity, and delayed puberty. can be caused by: (a) Lack of anterior pituitary growth hormone (b) Hypothalamic dysfunction (↓ GHRH) (c) Failure to generate IGF in the liver (d) Growth hormone receptor deficiency (2) Growth hormone excess can be treated with somatostatin analogs (e.g., octreotide), which inhibit growth hormone secretion. Hypersecretion of growth hormone causes acromegaly. (a) Before puberty, excess growth hormone causes increased linear growth (gigantism). (b) After puberty, excess growth hormone causes increased periosteal bone growth, increased organ size, and glucose intolerance Prolactin is the major hormone responsible for lactogenesis. participates, with estrogen, in breast development. is structurally homologous to growth hormone. a. Regulation of prolactin secretion (Figure 7-7 and Table 7-3) (1) Hypothalamic control by dopamine- and thyrotropin-releasing hormone (TRH) Prolactin secretion is tonically inhibited by dopamine [prolactin-inhibiting factor (PIF)] secreted by the hypothalamus. Thus, interruption of the hypothalamic – pituitary tract causes increased secretion of prolactin and sustained lactation. TRH increases prolactin secretion. (2) Negative feedback control Prolactin inhibits its own secretion by stimulating the hypothalamic release of dopamine. In persons who are not pregnant or lactating, prolactin secretion is tonically inhibited by dopamine (prolactin-inhibiting factor [PIF]) from the hypothalamus. (1) The major source of dopamine is dopaminergic neurons in the hypothalamus, which synthesize and secrete dopamine into the median eminence. This dopamine goes directly to the anterior pituitary, where it inhibits prolactin secretion. (2) Dopamine also is secreted by dopaminergic neurons of the posterior lobe of the pituitary, reaching the anterior lobe by short connecting portal veins. (3) Finally, nonlactotroph cells of the anterior pituitary secrete a small amount of dopamine that inhibits prolactin secretion by a paracrine mechanism. The factors that alter prolactin secretion are summarized in Table 9.5. Prolactin inhibits its own secretion by increasing the synthesis and secretion of dopamine from the hypothalamus (see Fig. 9.12). This action of prolactin constitutes negative feedback because stimulation of dopamine secretion causes inhibition of prolactin secretion. Pregnancy and breast-feeding (suckling) are the most important stimuli for prolactin secretion. Actions of prolactin (1) Stimulates milk production in the breast (casein, lactalbumin) (2) Stimulates breast development with estrogen (3) Inhibits ovulation by decreasing synthesis and release of (GnRH) (4) Inhibits spermatogenesis (by decreasing GnRH) c. Pathophysiology of prolactin (1) Prolactin deficiency (destruction of the anterior pituitary) results in the failure to lactate. (2) Prolactin excess results from hypothalamic destruction (due to loss of the tonic “inhibitory” control by dopamine), or from prolactin-secreting tumors (prolactinomas). causes galactorrhea and decreased libido. causes failure to ovulate and amenorrhea because it inhibits GnRH secretion. can be treated with bromocriptine, which reduces prolactin secretion by acting as a dopamine agonist. POSTERIOR PITUITARY GLAND AND ITS RELATION TO THE HYPOTHALAMUS The posterior pituitary gland, also called the neurohypophysis, is composed mainly of glial-like cells called pituicytes. The pituicytes do not secrete hormones; they act simply as a supporting structure for large numbers of terminal nerve fibers and terminal nerve endings from nerve tracts that originate in the supraoptic and paraventricular nuclei of the hypothalamus,although both hormones are synthesized in both nuclei two posterior pituitary hormones: ADH is formed primarily in the supraoptic nuclei, oxytocin is formed primarily in the paraventricular nuclei. PHYSIOLOGICAL FUNCTIONS OF ANTIDIURETIC HORMONE ADH can cause decreased excretion of water by the kidneys (antidiuresis] Without ADH, the tubular epithelial cells of the collecting ducts are almost impermeable to water. ADH acts on the cell, it first combines with membrane receptors that activate adenylyl cyclase causes increase cAMP which causes phosporilation of special vesicles and then aquaporin insertion in cell membrane b. Actions of ADH (1) ↑ H2O permeability (aquaporin 2, AQP2) of the principal cells of the late distal tubule and collecting duct (via a V2 receptor and an adenylate cyclase– cAMP mechanism) (2) Constriction of vascular smooth muscle (via a V1 receptor and an IP3/Ca2+ mechanism) REGULATION OF ANTIDIURETIC HORMONE PRODUCTION 1.♦Increased Extracellular Fluid Osmolarity Stimulates ADH Secretion Somewhere in or near the hypothalamus are modified neuron receptors called osmoreceptors. When the extracellular fluid becomes too concentrated, fluid is pulled by osmosis out of the osmoreceptor cell, decreasing its size and initiating appropriate nerve signals in the hypothalamus to cause additional ADH secretion 2.♦ Contraction of vascular smooth muscle. The second action of ADH is to cause contraction of vascular smooth muscle (as implied by its other name, vasopressin). The receptor for ADH on vascular smooth muscle is a V1 receptor, which produces contraction of vascular smooth muscle, constriction of arterioles, and increased total peripheral resistance Central diabetes insipidus Central diabetes insipidus is caused by failure of the posterior pituitary to secrete ADH. In this disorder, circulating levels of ADH are low, the collecting ducts are impermeable to water, and the urine cannot be concentrated. Thus persons with central diabetes insipidus produce large volumes of dilute urine, and their body fluids become concentrated (e.g., increased serum osmolarity, increased serum Na+ concentration). Central diabetes insipidus is treated with an ADH analogue, dDAVP. In nephrogenic diabetes insipidus, the posteriorpituitary is normal but the principal cells of the collecting duct are unresponsive to ADH due to a defect in the V2 receptor, Gs protein, or adenylyl cyclase. As in central diabetes insipidus, water is not reabsorbed in the collecting ducts and the urine cannot be concentrated, resulting in excretion of large volumes of dilute urine. As a result, the body fluids become concentrated and the serum osmolarity increases. In contrast to central diabetes insipidus, however, ADH levels are elevated in nephrogenic diabetes insipidus due to stimulation of secretion by the increased serum osmolarity. Nephrogenic diabetes insipidus is treated with thiazide diuretics. In syndrome of inappropriate ADH (SIADH), excess ADH is secreted from an autonomous site High levels of ADH cause excess water reabsorption by the collecting ducts, which dilutes the body fluids. The urine is inappropriately concentrated (i.e., too concentrated for the serum osmolarity). SIADH is treated with an ADH antagonist such as demeclocycline or water restriction.  PHYSIOLOGICAL FUNCTIONS OF OXYTOCIN oxytocin causes milk to be expressed from the alveoli into the ducts of the breast so that the baby can obtain it by suckling. The suckling stimulus on the nipple of the breast causes signals to be transmitted through sensory nerves to the oxytocin neurons in the paraventricular and supraoptic nuclei in the hypothalamus, which causes release of oxytocin. Actions of oxytocin (1) Contraction of myoepithelial cells in the breast Milk is forced from the mammary alveoli into the ducts and delivered to the infant. (2) Oxytocin Causes Contraction of the Pregnant Uterus Contraction of the uterus During pregnancy, oxytocin receptors in the uterus are up-regulated as parturition approaches, although the role of oxytocin in normal labor is uncertain. Oxytocin can be used to induce labor and reduce postpartum bleeding.