REGULATION OF HYPOTHALAMIC AND PITUITARY CORTICOTROPIN-RELEASING HORMONE-RECEPTOR MESSENGER-RIBONUCLEIC-ACID BY ADRENALECTOMY AND GLUCOCORTICOIDS

The effects of adrenalectomy and glucocorticoids on the regulation of corticotropin-releasing hormone (CRH) receptor expression in the hypot halamic paraventricular nucleus (PVN) and pituitary were studied by in situ hybridization in the rat using a complementary RNA probe directe d toward the coding region of the type 1 CRH receptor. Eighteen hours after adrenalectomy, CRH receptor messenger RNA (mRNA) expression in t he PVN was significantly increased, whereas longer term adrenalectomy (4 and 6 days) had no effect. This transient effect of adrenalectomy w as prevented by glucocorticoid replacement. In intact rats, 4 h after immobilization for 1 h or a single ip hypertonic saline injection, CRH receptor mRNA in the PVN markedly increased (P < 0.01), an effect tha t was unchanged by adrenalectomy (4 or 6 days) or dexamethasone inject ion (100 mu g at -14 and 50 mu g at -1 h) before stress. In the pituit ary, CRH receptor mRNA levels decreased transiently after adrenalectom y (-62% after 18 h), returning to basal levels 4 or 6 days after adren alectomy. The early decrease was prevented by glucocorticoid replaceme nt. In intact rats, dexamethasone (100 mu g, sc) caused a significant decrease in pituitary CRH receptor mRNA levels 2-10 h after injection, returning to basal levels after 15 h. On the other hand, dexamethason e (5-300 mu g, sc) had no effect on pituitary CRH receptor mRNA levels 18 h after injection. The data show that although stress stimulation of CRH mRNA in the PVN is glucocorticoid independent, basal levels are likely to be under dual, transcriptional and posttranscriptional, con trol by glucocorticoids. In the pituitary, changes in hypothalamic CRF s probably play a major role in the control of CRH receptor mRNA level s during manipulations of circulating glucocorticoids levels. In addit ion, the inability of long term adrenalectomy and glucocorticoid admin istration to modify pituitary CRH receptor mRNA levels suggests that C RH receptor down-regulation observed under these experimental conditio ns depends mainly on translational and posttranslational events rather than receptor mRNA levels.