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In other cases, hormones may affect(upward or downward) the number of receptors for a differenthormone. This process is known as heterologous regulation.POSTERIOR PITUITARY HORMONESADH and oxytocin are both nonapeptides (nine amino acidpeptides) derived from preprohormones synthesized by hypothalamic nuclei.
Cleavage of the preprohormones producesneurophysins along with ADH and oxytocin. The neurophysins function as carrier proteins as ADH and oxytocin aretransported in vesicles down the axons of the neurons inwhich they are synthesized and into the posterior pituitary.The hormone-containing vesicles are stored in nerve endingswithin the posterior lobe of the pituitary. When the hypothalamic neuron is depolarized, the action potential is propagated along the axon to the nerve terminal, where Ca2+ influxoccurs and results in exocytosis of vesicular contents.Antidiuretic Hormone (ADH)As implied by its name, ADH is secreted during conditions inwhich water retention (“antidiuresis”) is required for homeostasis. The synthesis, release, and physiological actions ofADH are illustrated in Figure 26.6 and described further inChapters 12 and 18.
In addition to its antidiuretic effect, it isalso a vasopressor, causing contraction of vascular smoothmuscle (thus, the name “vasopressin”). Therefore, ADH isreleased mainly in response to one of two stimuli:■■Hyperosmolarity of plasma, detected by osmoreceptorswithin the hypothalamus.Hypovolemia and hypotension, detected by arterial andatrial baroreceptors.Hyperosmolarity (caused, for example, by fluid deprivationor dehydration) is normally much more important thanhypovolemia or hypotension in terms of stimulation of ADHsecretion. Although normal variation of blood pressure is notGeneral Principles of Endocrinology and Pituitary and Hypothalamic HormonesNegative FeedbackPositive FeedbackHypothalamusHypothalamus⫹⫺⫹Anteriorpituitary⫹⫹Anteriorpituitary⫺⫹⫹OvaryTestes⫹⫹EstradiolTestosterone⫹Target tissue(e.g., muscle)⫹Target tissue(e.g., breast,uterineendometrium)Figure 26.5 Negative and Positive Feedback Regulation In most cases, a hypothalamicpituitary-target gland axis is regulated by negative feedback, whereby the trophic hormone of the anteriorpituitary gland has negative feedback effects on the hypothalamus, and the target gland hormone has negative feedback effects on both the hypothalamus and the anterior pituitary.
Through these mechanisms,illustrated for the hypothalamus-pituitary-testes axis, levels of the target gland hormone are maintainedwithin the normal physiological range. In a few specific cases, positive feedback can also occur. Forexample, during the late follicular and ovulatory phases of the menstrual cycle, high levels of estradiol actually cause greater secretion of the hypothalamic releasing hormone and trophic hormones in that system,resulting in the surge in pituitary hormone release that is responsible for ovulation at midcycle.313314Endocrine PhysiologyStimulates ADH SecretionIncreased body fluid osmolalityDecreased blood volumeDecreased blood pressureAngiotensin IIPainStressNausea and vomiting+Inhibits ADH SecretionDecreased body fluid osmolalityIncreased blood volumeIncreased blood pressureAtrial natriuretic peptideEthanol–Water and electrolyteexchange between bloodand tissues: normal orpathological (edema)Cells in the paraventricularand supraoptic nuclei receiveinput from osmoreceptors(monitor changes in bodyfluid osmolality), peripheralbaroreceptors (monitor changesin blood pressure and volume),and higher neural centersFluid intake(oral or parenteral)Water and electrolyteloss via gut (vomiting,diarrhea), via cavities(ascites, effusion),or externally(sweat, hemorrhage)Antidiuretic hormonedescends nerve fibersand is picked up bycapillaries ofneurohypophysis90% of filteredwater reabsorbedin proximal tubuleand Henle’s loopdue to reabsorptionof salts, leaving 15to 20 L a dayAntidiuretichormone (ADHor vasopressin)H2ONa+Na+HOH2OH2O2Na+Na+Na+Na+Na+Na+OH2H2OH2OAntidiuretic hormone makes collectingtubule permeable to water, permittingits reabsorption due to high osmolalityof renal medullaNa+2ONa+HAntidiuretic hormone makesdistal convoluted tubule permeableto water and thus permits it to bereabsorbed along with activelyreabsorbed saltApproximately180 L offluid filteredfrom bloodplasma byglomeruli in24 hours14 to 16 L reabsorbed daily under influenceof antidiuretic hormone, resulting in 1 to 2 Lof urine in 24 hoursH2ONa+Na+Na+Na+Na+Na+Na+Na+Na+Ascending limb of Henle's loopimpermeable to water; activelyreabsorbs salt, creating highosmolality of renal medullaFigure 26.6 Posterior Pituitary Function (ADH) Antidiuretic hormone (ADH; also known as vasopressin) is synthesized mainly in the supraoptic nuclei (and also the paraventricular nuclei) of the hypothalamus and is stored and released at the posterior pituitary.
Its main function is in water balance; it is releasedin response to increased osmolarity of extracellular fluid and decreased blood pressure and has the majoreffect of promoting water reabsorption by the kidney. When ADH levels in plasma are high, a low volumeof concentrated urine is produced.a significant stimulus for ADH release, significant loss ofblood volume (for example, during hemorrhage) causes secretion of the hormone, which participates in blood pressurehomeostasis and fluid replenishment under those conditionsby stimulating water retention in the kidney and contractionof vascular smooth muscle.Physiological actions of the hormone are covered in greaterdetail in Chapter 18. To summarize (see Fig. 26.6), the actionsof ADH include effects on renal handling of water, specifically, increased permeability of the distal convoluted tubuleand collecting tubule to water, and thus increased waterreabsorption, by the kidney.OxytocinOxytocin, the other hormone released by the posterior pituitary, has a role in breastfeeding and in childbirth (Fig.
26.7).Thus, it is released in response to:■■breastfeedingcervical and vaginal stimulationGeneral Principles of Endocrinology and Pituitary and Hypothalamic Hormones315Psychogenic stimuliOxytocinmigratesalongnervefibersParaventricular nucleusof hypothalamus (site ofoxytocin production)Oxytocin pickedup by capillaries ofposterior lobeProlactin stimulatesmilk production inendocrinologicallyprepared breastAfferent impulsesfrom nippleOxytocin causesmilk expulsionOxytocin causesuterine contractionAfferent impulses fromcervical dilation orvaginal stimulationFigure 26.7 Posterior Pituitary Function (Oxytocin) Oxytocin is synthesized mainly in the paraventricular nuclei (and also the supraoptic nuclei) of the hypothalamus and is stored and released at theposterior pituitary.
Its main functions are to stimulate milk let-down and uterine contraction.During breastfeeding, oxytocin released by the neurohypophysis causes “let-down” or expulsion of milk from the mammaryglands of the breasts. The actual production of milk is stimulated specifically by a different hormone, prolactin. Distensionof the cervix and vagina also stimulates the release of oxytocin,and the hormone stimulates uterine contractions. However,its actual physiological role in induction or progression oflabor is not well established. Oxytocin is also released duringorgasm in both sexes and might have a role in sperm transportduring ejaculation of the male, as well as transport of spermwithin the female reproductive tract. Furthermore, oxytocinCLINICAL CORRELATEInduction of Labor by Synthetic OxytocinAlthough a physiological role for oxytocin in humans in induction or progression of labor is not well established, it stimulatesstrong uterine contractions when used at high doses as a drug.Thus, synthetic oxytocin is often used in clinical situations inwhich artificial induction or stimulation of the progression oflabor is medically required.
As is generally the case for peptidedrugs, it is not effective orally due to cleavage in the gastrointestinal tract, and it is administered by intravenous infusion.316Endocrine Physiologyappears to stimulate pair-bonding in mammals, includinghumans, through its central nervous system effects.■■ANTERIOR PITUITARY HORMONESThe six anterior pituitary hormones are peptides, proteins, orglycoproteins and are synthesized and secreted by distinct celltypes within the adenohypophysis:■■■■■Gonadotrophs produce the two gonadotropins (LH andFSH).Thyrotrophs synthesize thyroid-stimulating hormone(TSH).Corticotrophs synthesize adrenocorticotropic hormone(ACTH).Lactotrophs produce prolactin.Somatotrophs produce growth hormone (GH).Synthesis and secretion of these hormones is regulated byhypothalamic hormones that reach the anterior pituitary viathe hypophyseal portal circulation, as well as by various feedback loops.
In some cases, the hormones are mainly controlledby either a hypothalamic releasing hormone or an inhibitoryhormone; in others, there is dual control by a hypothalamicreleasing hormone and a hypothalamic inhibitory hormone.The anterior pituitary hormones are discussed in subsequentchapters in the context of their target gland hormones, withthe exception of growth hormone and prolactin.Growth hormone–releasing hormone (GHRH), whichstimulates growth hormone release, andSomatostatin, which inhibits growth hormone release.Most of the effects of growth hormone are not direct but aremediated by the synthesis and release of somatomedins by theliver and by stimulation of somatomedin production in specific target tissues.
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