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Hypothalamus and Pituitary Gland
The document discusses the hypothalamus and pituitary gland. It begins by reviewing the anatomy of the hypothalamus and its relation to the pituitary gland. It then describes the development of the pituitary gland from different embryonic tissues, with the posterior lobe deriving from neural tissue and the anterior lobe from epithelial tissue. The document goes on to explain the neurohypophysis and adenohypophysis in more detail, including the hormones produced and released in negative feedback loops.
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Hypothalamus and Pituitary Gland
- 1. Concept of Balance Homeostasisis necessary, in the long- term to maintain life.
- 2. Endocrine Physiology: The Hypothalamusand Pituitary Gland Demuel Dee L. Berto,MD
- 4. After the sessionthe first year medical student will be able to: • Review the important anatomic concepts about the hypothalamus and the pituitary gland • Describe the influence of hypothamic hormones to anterior pituitary gland hormonal regulation • Differentiate the anterior and posterior pituitary gland in terms of histology, hormonal production and release • Explain the Negative-feedback loops regulating hormone secretion in a typical hypothalamus- pituitary- peripheral gland axis. 4
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- 8. RELATION TO THEPITUITARY GLAND 8
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- 11. Development of thePituitary gland • The two lobes of the pituitary develop from different embryological Anterior Posterior tissues. lobe lobe •The POSTERIOR pituitary is neural tissue derived from primitive ectoderm. It develops as a downgrowth from the 3rd ventricle. •The ANTERIOR pituitary consists of epithelial tissue and develops upwards as an outgrowth from the Rathke pouch, an evagination from the roof of the pharynx.
- 12. Development of thePituitary Gland 1. Outgrowths of tissue begin to appear 3. The immature anterior pituitary from the hypothalamus and the roof of lobe separates from the roof of the the mouth mouth Infundibulum growing down Immature from floor of the 3rd anterior pituitary ventricle gland Outgrowth of epithelial roof of mouth cells growing up from the roof of the mouth 4. The anterior and posterior pituitary lobes mature and the bony sella turcica forms 2. The two outgrowths of tissue anterior posterior start to fuse together lobe lobe sella turcica
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- 24. Supraoptic Paraventricular Hypothalamus nucleus nucleus The anterior lobe is larger than the posterior Preoptic nucleus lobe and has three Neurosecretory parts: neurones Infundibulum • Pars tuberalis, • Pars distalis Anterior pituitary • Pars intermedia Posterior pituitary
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- 52. References • Physiology byBerne and Levy 6th edition • Medical Physiology by Guyton and Hall 11th edition • Review of Medical Physiology by Ganong 23rd edition 52
- 53. Thank you! 53
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Editor's Notes
- #3 textbook byGail Jenkins, Christopher Kemnitz, Gerard Tortora
- #7 The hypothalamus (Figure 18–1) is the portion of the anterior end of the diencephalon that lies below thehypothalamic sulcus and in front of the interpeduncular nuclei. It is divided into a variety of nuclei and nuclear areas.
- #8 The hypothalamus is the “integration centre” for many physiological processes in the body. The principal afferent and efferent neural pathways to and from the hypothalamus are mostly unmyelinated. Many connect the hypothalamus to the limbic system. Important connections also exist between the hypothalamus and nuclei in the midbrain tegmentum, pons, and hindbrain.
- #10 Gross structure of the pituitary gland. The pituitary gland is below the hypothalamus and is connected to it by the pituitary stalk. The gland sits within the sellaturcica, a fossa within the sphenoid bone, and is covered by a dural reflection, the diaphragmasellae. The pars distalis makes up most of the anterior pituitary. (Modified from Stevens A. In Lowe JS [ed]: Human Histology, 3rd ed. Philadelphia, Elsevier, 2005.)Microscopic examination of the pituitary reveals two distinct types of tissue: epithelial and neural (Fig. 40-2). The epithelial portion of the human pituitary gland is called the adenohypophysis. The adenohypophysismakes up the anterior portion of the pituitary and is often referred to as the anterior lobe of the pituitary, and its hormones are referred to as anterior pituitary hormones. The adenohypophysis is composed of three parts: (1) the pars distalis, which makes up about 90% of the adenohypophysis; (2) the pars tuberalis, which wraps around the stalk; and (3) the pars intermedia, which regresses and is absent in adult humans.The neural portion of the pituitary is called the neurohypophysis and it represents a down-growth of thehypothalamus. The lowest portion of the neurohypophysis is called the pars nervosa, which is also called theposterior lobe of the pituitary (or simply, the "posterior pituitary"). At the superior end of theneurohypophysis, a funnel-shaped swelling called the median eminence develops. The rest of theneurohypophysis, which extends from the median eminence down to the pars nervosa, is called theinfundibulum. The infundibulum and the pars tuberalis make up the pituitary stalk-a physical connectionbetween the hypothalamus and the pituitary gland (Fig. 40-2).
- #11 There are neural connections between the hypothalamus and the posterior lobe of the pituitary gland and vascular connections between the hypothalamus and the anterior lobe. Embryologically, the posterior pituitary arises as an evagination of the floor of the third ventricle. It is made up in large part of the endings of axons that arise from cell bodies in the supraoptic and paraventricular nuclei and pass to the posterior pituitary (Figure 18–2) via the hypothalamohypophysial tract.
- #15 Median eminence: the floor of the diencephalon.Infundibulum: the stalk connecting the median eminence to the posterior pituitary. Pars nervosa: the major portion of the posterior pituitary.Magnocellular neurons of the hypothalamus (paraventricular and supraoptic nuclei) project their axons down the infundibular process and terminate in the pars nervosa (posterior lobe), where they release their hormones (either ADH or oxytocin) into a capillary bed. (Modified from Larsen PR et al [eds]: Williams Textbook of Endocrinology, 10th ed. Philadelphia, Saunders, 2003.)THE NEUROHYPOPHYSISThe pars nervosa is a neurovascular structure that is the site of release of neurohormones adjacent to a richbed of fenestrated capillaries. The peptide hormones that are released are antidiuretic hormone (ADH, orarginine vasopressin) and oxytocin. The cell bodies of the neurons that project to the pars nervosa arelocated in the supraoptic nuclei (SON) and paraventricular nuclei (PVN) of the hypothalamus (in thiscontext, a "nucleus" refers to a collection of neuronal cell bodies residing within the central nervous system[CNS]-a "ganglion" is a collection of neuronal cell bodies residing outside the CNS). The cell bodies of theseneurons are described as magnocellular (i.e., large cell bodies), and they project axons down theinfundibular stalk as the hypothalamohypophysial tracts. These axons terminate in the pars nervosa (Fig.40-3). In addition to axonal processes and termini from the SON and PVN, there are glial-like supportive cellscalled pituicytes. The posterior pituitary is extensively vascularized and the capillaries are fenestrated, thereby facilitating diffusion of hormones into the vasculature.
- #16 Like other peptide hormones, the posterior lobe hormones are synthesized as part of larger precursor molecules. The precursor for arginine vasopressin, prepropressophysin, contains a 19-amino-acidresidue leader sequence followed by arginine vasopressin, neurophysin II, and a glycopeptide (Figure 18–7). Preprooxyphysin,the precursor for oxytocin, is a similar but smaller molecule that lacks the glycopeptide.Vasopressin and oxytocin each have a characteristic neurophysin associated with them in the granules in the neurons that secrete them—neurophysin I in the case of oxytocin and neurophysin II in the case of vasopressin. The neurophysins were originally thought to be binding polypeptides, but it now appears that they are simply parts of the precursor molecules.
- #17 The precursor molecules are synthesized in the ribosomes of the cell bodies of the neurons. They have their leader sequences removed in the endoplasmic reticulum, are packaged into secretory granules in the Golgi apparatus, and are transported down the axons by axoplasmic flow to the endings in the posterior pituitary. The secretory granules, called Herring bodies, are easy to stain in tissue sections, and they have been extensively studied. Cleavage of the precursor molecules occurs as they are being transported, and the storage granules in the endings contain freevasopressin or oxytocin and the corresponding neurophysin. In the case of vasopressin, the glycopeptide is alsopresent. All these products are secreted, but the functions of the components other than the established posteriorpituitary hormones are unknown.Figure 40-5 Synthesis, processing, and transport of preprovasopressin. Human ADH (also called argininevasopressin or AVP) is synthesized in the hypothalamic magnocellular cell bodies and packaged intoneurosecretory granules. During intraaxonal transport of the granules down the infundibular process to thepars nervosa, provasopressin is proteolytically cleaved into the active hormone (AVP = ADH), neurophysin(NP), and a C-terminal glycoprotein (GP). NP arranges into tetramers that bind five AVP molecules. All threefragments are secreted from axonal termini in the pars nervosa (posterior pituitary) and enter the systemicblood. Only AVP (ADH) is biologically active. (Modified from Larsen PR et al [eds]: Williams Textbook ofEndocrinology, 10th ed. Philadelphia, Saunders, 2003.)ADH and oxytocin are released from the pars nervosa in response to stimuli that are primarily detected at thecell body and its dendrites in the SON and PVN of the hypothalamus. The stimuli are mainly in the form ofneurotransmitters released from hypothalamic interneurons. With sufficient stimulus, the neurons willdepolarize and propagate an action potential down the axon. At the axonal termini, the action potentialincreases intracellular [Ca++] and results in a stimulus-secretion response, with the exocytosis of ADH oroxytocin, along with neurophysins, into the extracellular fluid of the pars nervosa (Fig. 40-5). Hormones andneurophysins enter the peripheral circulation, and both can be measured in blood.
- #18 The oxytocin-secreting and vasopressin-secreting neurons also generate and conduct action potentials, and actionpotentials reaching their endings trigger release of hormone from them by Ca2+-dependent exocytosis. At least inanesthetized rats, these neurons are silent at rest or discharge at low, irregular rates (0.1–3 spikes/s). However,their response to stimulation varies (Figure 18–8). Stimulation of the nipples causes a synchronous, high-frequencydischarge of the oxytocin neurons after an appreciable latency. This discharge causes release of a pulse of oxytocinand consequent milk ejection in postpartum females.
- #19 Figure 43-39 Neuroendocrine reflex caused by suckling at the nipple and leading to secretion ofoxytocin and prolactin. In turn, these hormones induce continued milk production (galactopoiesis) andmilk let-down. Prolactin also induces lactational amenorrhea. (Modified from Porterfield SP, White BA:Endocrine Physiology, 3rd ed. Philadelphia, Mosby, 2007.)Suckling at the nipple also stimulates the release of oxytocin from the pars nervosa (see Chapter 40)through a neuroendocrine reflex (Fig. 43-39). Contraction of myoepithelial cells induces milk letdown,or expulsion of milk from the alveolar and ductal lumens. Thus, the nursing infant does not gainmilk by applying negative pressure to the breast from suckling. Rather, milk is actively ejected througha neuroendocrine reflex. Oxytocin release and milk let-down can be induced by psychogenic stimuli,such as the mother hearing a baby crying on television or thinking about her baby. Such psychogenicstimuli do not affect PRL release.
- #20 In humans, oxytocin acts primarily on the breasts and uterus, though it appears to be involved in luteolysis as well(see Chapter 25). A G protein-coupled serpentine oxytocin receptor has been identified in human myometrium, and asimilar or identical receptor is found in mammary tissue and the ovary. It triggers increases in intracellular Ca2+levels.Oxytocin causes contraction of the smooth muscle of the uterus. The sensitivity of the uterine musculature to oxytocinis enhanced by estrogen and inhibited by progesterone. The inhibitory effect of progesterone is due to a direct actionof the steroid on uterine oxytocin receptors. In late pregnancy, the uterus becomes very sensitive to oxytocincoincident with a marked increase in the number of oxytocin receptors and oxytocin receptor mRNA (see Chapter 25).Oxytocin secretion is increased during labor. After dilation of the cervix, descent of the fetus down the birth canalinitiates impulses in the afferent nerves that are relayed to the supraoptic and paraventricular nuclei, causingsecretion of sufficient oxytocin to enhance labor (Figure 25-32). The amount of oxytocin in plasma is normal at theonset of labor. It is possible that the marked increase in oxytocin receptors at this time causes normal oxytocin levelsto initiate contractions, setting up a positive feedback. However, the amount of oxytocin in the uterus is alsoincreased, and locally produced oxytocin may also play a role.
- #21 On the other hand, stimulation of the vasopressin-secreting neurons by a stimulus such as hemorrhage causes an initial steady increase in firing rate followed by a prolonged pattern of phasic discharge in which periods of high-frequency discharge alternate with periods of electrical quiescence (phasic bursting). These phasic bursts are generally not synchronous in different vasopressin-secreting neurons.They are well suited to maintain a prolonged increase in the output of vasopressin, as opposed to the synchronous,relatively short, high-frequency discharge of oxytocin-secreting neurons in response to stimulation of the nipples.
- #22 The total body osmolality is directly proportional to the total body sodium plus the total body potassium divided bythe total body water, so that changes in the osmolality of the body fluids occur when a disproportion exists betweenthe amount of these electrolytes and the amount of water ingested or lost from the body. When the effective osmoticpressure of the plasma rises, vasopressin secretion is increased and the thirst mechanism is stimulated; water isretained in the body, diluting the hypertonic plasma; and water intake is increased (Figure 39–1). Conversely, whenthe plasma becomes hypotonic, vasopressin secretion is decreased and "solute-free water" (water in excess ofsolute) is excreted. In this way, the tonicity of the body fluids is maintained within a narrow normal range.
- #23 The actions of ADH on permeability of the collecting duct to water have been studied extensively. ADH binds to a receptor on the basolateral membrane of the cell. This receptor is termed the V2 receptor(i.e., vasopressin 2 receptor).* Binding to this receptor, which is coupled to adenylylcyclase via astimulatory G protein (Gs), increases intracellular levels of cAMP. The rise in intracellular cAMPactivates protein kinase A (PKA), which ultimately results in the insertion of vesicles containingaquaporin-2 (AQP2) water channels into the apical membrane of the cell, as well as the synthesis ofmore AQP2 (Fig. 34-3). With the removal of ADH, these water channels are reinternalized into the cell,and the apical membrane is once again impermeable to water. This shuttling of water channels intoand out of the apical membrane provides a rapid mechanism for controlling permeability of themembrane to water. Because the basolateral membrane is freely permeable to water as a result of thepresence of AQP3 and AQP4 water channels, any water that enters the cell through apical membranewater channels exits across the basolateral membrane, thereby resulting in net absorption of waterfrom the tubule lumen. In addition to the acute effects of ADH just described, ADH regulates the expression of AQP2 (andAQP3). When large volumes of water are ingested over an extended period (e.g., psychogenicpolydipsia), expression of AQP2 and AQP3 in the collecting duct is reduced. As a consequence, whenwater ingestion is restricted, these individuals cannot maximally concentrate their urine. Conversely, instates of restricted water ingestion, expression of AQP2 and AQP3 in the collecting duct increases andthus facilitates the excretion of maximally concentrated urine.It increases the permeability of the collecting ducts of the kidney, so that waterenters the hypertonic interstitium of the renal pyramids. The urine becomes concentrated, and its volume decreases.The overall effect is therefore retention of water in excess of solute; consequently, the effective osmotic pressure ofthe body fluids is decreased. In the absence of vasopressin, the urine is hypotonic to plasma, urine volume isincreased, and there is a net water loss. Consequently, the osmolality of the body fluid rises.The mechanism by which vasopressin exerts its antidiuretic effect is activated by V2 receptors and involves theinsertion of proteins called water channels into the apical (luminal) membranes of the principal cells of the collectingducts. Movement of water across membranes by simple diffusion is now known to be augmented by movementthrough water channels called aquaporins, and to date 13 (AQP0–AQP12) have been identified and water channelsare now known to be expressed in almost all tissues in the body. The vasopressin-responsive water channel in thecollecting ducts is aquaporin-2. These channels are stored in endosomes inside the cells, and vasopressin causes theirrapid translocation to the luminal membranes.It is also clear that expression of AQP2 (and in some instances also AQP3) varies in pathologicalconditions associated with disturbances in urine concentration and dilution. As discussed elsewhere,AQP2 expression is reduced in a number of conditions associated with impaired urine-concentratingability. By contrast, in conditions associated with water retention, such as congestive heart failure,hepatic cirrhosis, and pregnancy, AQP2 expression is increased.ADH also increases the permeability of the terminal portion of the inner medullary collecting duct tourea. This results in an increase in reabsorption of urea and an increase in the osmolality of themedullary interstitial fluid. The apical membrane of medullary collecting duct cells contains two differenturea transporters (UT-A1 and UT-A3).* ADH, acting through the cAMP/PKA cascade, increasespermeability of the apical membrane to urea. This increase in permeability is associated withphosphorylation of UT-A1 and perhaps also UT-A3. Increasing the osmolality of the interstitial fluid ofthe renal medulla also increases the permeability of the collecting duct to urea. This effect is mediatedby the phospholipase C pathway and involves phosphorylation of protein kinase C. Thus, this effect isseparate and additive to that of ADH.In addition to its acute effect on permeability of the collecting duct to urea, ADH also increases theabundance of UT-A1 in states of chronic water restriction. In contrast, with water loading (i.e.,suppressed ADH levels), UT-A1 abundance in the collecting duct is reduced.ADH also stimulates reabsorption of NaCl by the thick ascending limb of Henle's loop and by the distaltubule and cortical segment of the collecting duct. This increase in Na+ reabsorption is associated withincreased abundance of key Na+ transporters: 1Na+-1K+-2Cl- symporter (thick ascending limb ofHenle's loop), Na+-Cl- symporter (distal tubule), and the epithelial Na+ channel (ENaC, in the distaltubule and collecting duct). It is thought that stimulation of NaCl transport by the thick ascending limbmay help maintain the hyperosmoticmedullaryinterstitium that is necessary for the absorption of waterfrom the medullary portion of the collecting duct (see later).
- #25 Pars distalis or pars anterior: the major portion of the anterior pituitary.Pars intermedia: a part continuous with the anterior pituitary and containing colloid filled epithelial cysts derived from the remnants of Rathke’s pouch.Pars tuberalis: a sheath of anterior pituitary wrapped around the infundibulum of the posterior pituitary.
- #26 Alpha Cell - somatotropesEpsilon acidophil cell – lactotropesBeta cell - Delta basophil cell - gonadotropesGamma cell
- #28 Each endocrine axis is composed of three levels of endocrine cells:(1) hypothalamic neurons, (2) anterior pituitary cells, and (3) peripheral endocrine glands. Hypothalamicneurons release specific hypothalamic releasing hormones (XRHs) that stimulate the secretion of specificpituitary tropic hormones (XTHs). In some cases, production of a pituitary tropic hormone is secondarilyregulated by a release-inhibiting hormone (XIH). Pituitary tropic hormones then act on specific peripheraltarget endocrine glands and stimulate them to release peripheral hormones (X). The peripheral hormone X hastwo general functions: it regulates several aspects of human physiology, and it negatively feeds back on thepituitary gland and hypothalamus to inhibit the production and secretion of tropic hormones and releasinghormones, respectively (Fig. 40-6).
- #29 The hypothalamic level of regulation is neurohormonal. Collections of neuronal cell bodies (called nuclei) reside in several regions of the hypothalamus and are collectively referred to as the hypophysiotropic (i.e., "stimulatory to the hypophysis" [= pituitary]) region of the hypothalamus. These nuclei are distinguished from the magnocellular neurons of the PVN and SON that project to the pars nervosa in that they have small, or parvicellular, neuronal cell bodies that project axons to the median eminence.
- #30 Location of cell bodies of hypophysiotropic hormone-secreting neurons projected on a ventral view of thehypothalamus and pituitary of the rat. AL, anterior lobe; ARC, arcuate nucleus; BA, basilar artery; DA, dopamine; IC,internal carotid artery; IL, intermediate lobe; MC, middle cerebral artery; ME, median eminence; PC, posterior cerebralartery; Peri, periventricular nucleus; PL, posterior lobe; PV, paraventricular nucleus; SO, supraoptic nucleus. The namesof the hormones are enclosed in boxes.The area from which the hypothalamic releasing and inhibiting hormones are secreted is the median eminence of thehypothalamus. This region contains few nerve cell bodies, but many nerve endings are in close proximity to thecapillary loops from which the portal vessels originate.The locations of the cell bodies of the neurons that project to the external layer of the median eminence and secretethe hypophysiotropic hormones are shown in Figure 18–12, which also shows the location of the neurons secretingoxytocin and vasopressin. The GnRH-secreting neurons are primarily in the medial preoptic area, the somatostatin secretingneurons are in the periventricular nuclei, the TRH-secreting and CRH-secreting neurons are in the medialparts of the paraventricular nuclei, and the GRH-secreting and dopamine-secreting neurons are in the arcuate nuclei.Receptors for most of the hypophysiotropic hormones are serpentine and coupled to G proteins. There are two humanCRH receptors: hCRH-RI, and hCRHRII. The latter differs from the former in having a 29-amino-acid insert in its firstcytoplasmic loop. The physiologic role of hCRH-RII is unsettled, though it is found in many parts of the brain. Inaddition, a CRH-binding protein in the peripheral circulation inactivates CRH. It is also found in the cytoplasm ofcorticotropes in the anterior pituitary, and in this location it might play a role in receptor internalization. However, the
- #31 There are six established hypothalamic releasing and inhibiting hormones (Figure 18–10): corticotropin-releasinghormone (CRH); thyrotropin-releasing hormone (TRH); growth hormone-releasing hormone (GRH);growth hormone-inhibiting hormone (GIH), now generally called somatostatin; luteinizing hormonereleasinghormone (LHRH), now generally known as gonadotropin-releasing hormone (GnRH); andprolactin-inhibiting hormone (PIH). In addition, hypothalamic extracts contain prolactin-releasing activity, and aprolactin-releasing hormone (PRH) has been postulated to exist. TRH, VIP, and several other polypeptides foundin the hypothalamus stimulate prolactin secretion, but it is uncertain whether one or more of these peptides is thephysiologic PRH. Recently, an orphan receptor was isolated from the anterior pituitary, and the search for its ligandled to the isolation of a 31-amino-acid polypeptide from the human hypothalamus. This polypeptide stimulatedprolactin secretion by an action on the anterior pituitary receptor, but additional research is needed to determine if itis the physiologic PRH. GnRH stimulates the secretion of FSH as well as that of LH, and it seems unlikely that aseparate follicle-stimulating hormone-releasing hormone exists.
- #33 The somatotrope produces growth hormone (GH, also called somatotropin) and is part of thehypothalamus-pituitary-liver axis (Fig. 40-17). A major target of GH is the liver, where it stimulates theproduction of insulin-like growth factor type I (IGF-I). GH is a 191-amino acid protein that is similar toprolactin (PRL) and human placental lactogen (hPL); accordingly, there is some overlap in activity amongthese hormones. Multiple forms of GH are present in serum and constitute a "family of hormones," with the191-amino acid (22-kDa) form representing approximately 75% of the circulating GH. The GH receptor is amember of the cytokine/GH/PRL/erythropoietin receptor family and, as such, is linked to the JAK/STATsignaling pathway (see Chapter 3). Human GH can also act as an agonist for the PRL receptor. About 50% ofthe 22-kDa form of GH in serum is bound to the N-terminal portion (the extracellular domain) of the GHreceptor and is called GH-binding protein (GHBP).The JAK-STAT signaling pathway transmits information from chemical signals outside the cell, through the cell membrane, and into gene promoters on the DNA in the cell nucleus, which causes DNA transcription and activity in the cell. The JAK-STAT system is a major signaling alternative to the second messenger system.The JAK-STAT system consists of three main components: (1) a receptor (2) Janus kinase (JAK) and (3) Signal Transducer and Activator of Transcription (STAT).[1]Many JAK-STAT pathways are expressed in white blood cells, and are therefore involved in regulation of the immune system.The receptor is activated by a signal from interferon, interleukin, growth factors, or other chemical messengers. This activates the kinase function of JAK, which autophosphorylates itself (phosphate groups act as "on" and "off" switches on proteins). The STAT protein then binds to the phosphorylated receptor, where STAT is phosphorylated itself. The phosphorylated STAT protein binds to another phosphorylated STAT protein (dimerizes) and translocates into the cell nucleus. In the nucleus, it binds to DNA and promotes transcription of genes responsive to STAT.In mammals, there are seven STAT genes, and each one binds to a different DNA sequence. STAT binds to a DNA sequence called a promoter, which controls the expression of other DNA sequences. This affects basic cell functions, like cell growth, differentiation and death.[1]The JAK-STAT pathway is evolutionarily conserved, from slime molds and worms to mammals (but not fungi or plants). Disrupted or dysregulated JAK-STAT functionality (which is usually by inherited or acquired genetic defects) can result in immune deficiency syndromes and cancers.[1]
- #38 Laron dwarfs, who lack normal GH receptors but have normal GH secretion, do not have detectable GHBP in their serum. GHBP reduces renal clearance and thus increases the biological half-life of GH, which is about 20 minutes. The liver and kidney are major sites of GH degradation.
- #42 The lactotrope produces the hormone prolactin, which is a 199-amino acid, single-chain protein. PRL isstructurally related to GH and hPL (see Chapter 43). Like GH, the PRL receptor is a member of the cytokinefamily coupled to the JAK/STAT signaling pathways. Because the primary action of PRL in humans is relatedto breast development and function during pregnancy and lactation, the regulation and actions of prolactin willbe discussed in detail in Chapter 43.In the context of the pituitary gland, it should be appreciated that the lactotrope differs from the other endocrinecell types of the adenohypophysis in two major ways:1. The lactotrope is not part of an endocrine axis. This means that PRL acts directly on nonendocrine cells(primarily of the breast) to induce physiological changes.2. Production and secretion of PRL are predominantly under inhibitory control by the hypothalamus. Thus,disruption of the pituitary stalk and the hypothalamohypophysial portal vessels (e.g., secondary tosurgery or physical trauma) results in an increase in PRL levels but a decrease in ACTH, TSH, FSH, LH,and GH.
- #44 CorticotropesCorticotropes stimulate (i.e., are "tropic to") the adrenal cortex as part of the hypothalamic-pituitary-adrenal(HPA) axis. Corticotropes produce the hormone adrenocorticotropic hormone (ACTH; also calledcorticotropin), which stimulates two zones of the adrenal cortex (see Chapter 42). ACTH is a 39-amino acidpeptide that is synthesized as part of a larger prohormone, proopiomelanocortin (POMC). Thus,corticotropes are also referred to as POMC cells. POMC harbors the peptide sequence for ACTH, forms ofmelanocyte-stimulating hormone (MSH), endorphins (endogenous opioids), and enkephalins (Fig. 40-8). Thehuman corticotrope expresses only the prohormoneconvertase, which produces ACTH as the sole activehormone secreted from these cells. The other fragments that are cleaved from POMC are the N-terminalfragment and β-lipotropic hormone (β-LPH). Neither of these fragments play a physiological role in humans.ACTH circulates as an unbound hormone and has a short half-life of about 10 minutes. It binds to themelanocortin 2 receptor (MC2R) on cells in the adrenal cortex (Fig. 40-9). ACTH acutely increases cortisoland adrenal androgen production, increases the expression of steroidogenic enzyme genes, and in the longterm, promotes the growth and survival of two zones in the adrenal cortex (see Chapter 42).At supraphysiological levels, ACTH causes darkening of light-colored skin (e.g.,Cushing's disease). Normally, keratinocytes express the POMC gene but process it to α-MSH instead of ACTH. Keratinocytes secrete α-MSH in response to ultraviolet light,and α-MSH acts as a paracrine factor on neighboringmelanocytes to darken the skin. α-MSH binds to the MC1R on melanocytes. However, at high levels, ACTH can alsocross-react with the MC1R receptor on skin melanocytes (Fig. 40-9). Thus, darkeningof skin is one indicator of excessive ACTH levels.