REGULATION OF CORTICOTROPIN-RELEASING HORMONE-RECEPTOR MESSENGER-RIBONUCLEIC-ACID IN THE RAT-BRAIN AND PITUITARY BY GLUCOCORTICOIDS AND STRESS

Glucocorticoids and stress are known to influence the synthesis of cor ticotropin-releasing hormone (CRH) at a variety of sites in brain, inc luding the hypothalamus and amygdala. The recent cloning of the CRH re ceptor (CRH-R) enabled us to determine whether glucocorticoids or stre ss influenced CRH action via regulation of CRH-R. We, therefore, used in situ. hybridization to measure CRH-R messenger RNA (mRNA) levels in the hypothalamic paraventricular nucleus (PVN), anterior pituitary (A P), amygdala, and bed nucleus of the stria terminalis (BNST) under sev eral conditions. Systemic corticosterone (CORT) treatment, both daily injection (5 mg/rat . day) up to 14 days and pellet implant (200 mg) f or 14 days, decreased CRH-R mRNA in the PVN and lateral and basolatera l nucleus of the amygdala (BLA). Corticosterone injection (10 mg/rat . day, for 7 days) decreased CRH-R mRNA in the AP. Adrenalectomy also d ecreased CRH-R mRNA in the PVN and AP, but did not alter it in the BLA . In both sham and adrenalectomized rats with CORT pellet replacement (39 mg; ADX + CORT rats), acute (2-h) and repeated (2 h daily for 14 d ays) immobilization stress (which produced a large increase in plasma CORT in sham rats) increased CRH-R mRNA in the PVN and decreased it in the AP, but did not affect CRH-R mRNA in the BLA. However, ADX + CORT rats consistently had higher levels of CRH-R mRNA in both the PVN and AP than sham rats after stress. Brain stem hemisection, which damaged all ascending catecholaminergic fibers with the exception of the locu s ceruleus, attenuated immobilization stress-induced up-regulation of CRH-R mRNA ipsilaterally in the PVN. None of the treatments affected C RH-R mRNA levels in the central and medial nucleus of the amygdala or the BNST. These results suggest that high concentrations of CORT or CR H synergistically decrease CRH-R mRNA levels in the AP, and that at le ast high CORT has an inhibitory effect on PVN CRH-R mRNA levels. Howev er, stress input can override such inhibitory effects and thus up-regu late CRH-R mRNA in the PVN. The extrahypothalamic regions, such as amy gdala and BNST may have different sensitivities to CORT or CRH for the regulation of CRH-R mRNA.