Glucocorticosteroids up-regulate the expression of cholecystokinin mRNA inthe rat paraventricular nucleus

Adrenalectomy abolishes corticosteroid feedback onto the hypothalamic-pitui tary-adrenal axis. This results in an increased biosynthetic and secretory activity of corticotropin-releasing hormone (CRH) neurons of the hypothalam ic paraventricular nucleus (PVN), sustained in the absence of hormone repla cement. In the PVN, cholecystokinin (CCK) is present both in parvicellular CRH-containing and in magnocellular oxytocin (OXY)-containing neurons. We p resently studied the glucocorticoid feedback regulation of thr expression o f cholecystokinin (CCK) mRNA in rats after: (i) adrenalectomy (ii) sham sur gery or (iii) adrenalectomy with corticosterone replacement. Using S-35-lab eled CRH and p-CCK cRNA probes and in situ hybridization, CRH and CCK mRNAs were radiolabeled. The total amount of hybridization labeling (integrated density), was quantified in adjacent series of cryosections regularly space d throughout the PVN. The OXY mRNA detection served to identify PVN magnoce llular areas. Adrenalectomy was shown to induce: (i) a 75% increase in CRH mRNA labeling in the PVN, (ii) a concomitant 43% decrease in CCK mRNA label ing but only in the anterior part of the PVN and occurring both in CCK/CRH area (two thirds of it) and CCK/OXY area tone third of it) and (iii) that t hey were fully reversed by corticosterone replacement. Thus, glucocorticoid s that are well known to negatively feedback on CRH expression in parvicell ular PVN neurons are also capable of positively regulating CCK expression i n anterior PVN neurons, both in parvicellular and magnocellular areas. (C) 2000 Elsevier Science B.V. All rights reserved.