Differential regulation of corticotropin-releasing hormone and vasopressintranscription by glucocorticoids

CRH and vasopressin (VP), the main regulators of pituitary ACTH secretion, co-exist in parvocellular cells of the PVN, but their levels of expression are regulated differentially during manipulations of the hypothalamic pitui tary adrenal (HPA) axis. The effects of glucocorticoids on this system was studied using in situ hybridization with intronic and exonic probes to meas ure changes in CRH and VP messenger RNA (mRNA) and heteronuclear (hn) RNA i n 48-h adrenalectomized (ADX) rats receiving injections of corticosterone ( 2.8 mg/ 100 g, ip) or vehicle. We also determined the time course of change s in VP expression following the first 12 h of ADX Levels of VP heteronucle ar Om) RNA and the number of parvocellular cells containing VP hnRNA remain ed very low in sham operated rats, whereas biphasic changes were observed a fter ADX. Grain density levels increased 11.5-fold over sham-operated contr ols by 6 h, declined to 2-fold by 18 h, to increase again to 10- and 20-fol d by 48 and 72 h, respectively. In 48-h ADX rats, vehicle injection increas ed CRH hnRNA levels transiently (11-fold the basal by 15 and 30 min), retur ning to basal at 60 min, whereas VP hnRNA levels increased progressively up to 28-fold the basal by 2 h. Corticosterone injection had no significant e ffect on vehicle-induced increases in CRH hnRNA, in spite of marked elevati ons in circulating corticosterone. In contrast to CRH; VP hnRNA levels incr eased only transiently by 15 min, and then decreased below basal (near sham -ADX levels) by 2 h. The data show that in normal conditions the responsive ness of parvocellular neurons to stress is under marked inhibition by the l ow resting levels of glucocorticoids, and that the sensitivity of CRH and V P transcription to glucocorticoid feedback is markedly different.