740 SECTION8Berne & Levy Physiology •Fig. 41.7 Neurovascularlinkbetweenthehypothalamusandtheanteriorlobe(parsdistalis)ofthepitu-itary.Parvicellular“hypophysiotropic”neurosecretoryneuronswithinvarioushypothalamicnucleiprojectaxonstothemedianeminence,wheretheysecretereleasinghormones(RHs).RHsflowdownthepituitarystalkinthehypothalamohypophysealportalvesselstotheanteriorpituitary.RHs(andrelease-inhibitinghormones[seetext])regulatesecretionoftropichormonesfromthefivecelltypesoftheanteriorpituitary.(FromLarsenPRetal[eds].Williams Textbook of Endocrinology. 10thed.Philadelphia:Saunders;2003.)Hormone-secreting cells Anterior lobe of pituitary Capillary beds Hypothalamohypophyseal portal vessels Hypothalamus Median eminence Parvocellular neurosecretory cells Hypophysiotropic hormones released Hormone transport in axons Hormone transport in blood Hormone transport in blood Stimulation or inhibition of anterior pituitary hormone release Action on endocrine glands
ACTH circulates as an unbound hormone and has a short half-life of about 10 minutes. It binds to the melanocortin-2 receptor (MC2R) on cells in the adrenal cortex (
Fig. 41.9 ). ACTH acutely increases cortisol and adrenal androgen production by increasing expression of steroidogenic enzyme genes. In the long term, ACTH promotes growth and survival of two zones within the adrenal cortex (see
ACTH is under stimulatory control by the hypothalamus. A subset of parvocellular hypothalamic neurons expresses the peptide procorticotropin-releasing hormone (pro-CRH) (see
Table 41.1).
Pro-CRH is processed to CRH, an amidated 41–amino acid peptide. CRH acutely stimulates ACTH secretion and increases transcription of the POMC gene. The parvocellular neurons that express CRH also express ADH, which potentiates the action of CRH on corticotropes. ACTH secretion has a pronounced diurnal pattern, with a peak in early morning and a nadir
Atsupraphysiologicallevels,ACTH causesdarkeningoftheskin(e.g.,inCushing’sdisease).KeratinocytesinthebasallayeroftheepidermisalsoexpressthePOMCgenebutprocessittoα-MSH insteadofACTH.Keratinocytessecreteα-MSHinresponsetoultravioletlight,andα-MSHactsasaparacrinefactoronneighboringmelanocytestodarkentheskin.α-MSHbindstotheMC1R onmelanocytes.Atveryhighlevels,ACTHcancross-reactwiththeMC1Rreceptoronskinmelanocytes(see
Fig.41.9 ).ThusincreasedskinpigmentationisoneindicatorofexcesscirculatingACTH.
Fig. 41.10).
In addition, secretion of CRH—and hence secretion of ACTH—is pulsatile.
There are multiple regulators of the HPA axis, and many of them are mediated through the CNS (
Fig. 41.11). Many types of stress, both neurogenic (e.g., fear) and systemic
TABLE 41.1