Novel corticotropin-releasing hormone receptor (CRHR), designated type-2alpha CRHR (CRHR-2alpha), was recently cloned and functionally characterized. In situ hybridization study revealed that CRHR-2alpha mRNA had a distinct distribution from type-1 CRHR (CRHR-1) mRNA in the rat brain. Interestingly, CRHR-2alpha mRNA showed a relatively high expression in the hypothalamic paraventricular nucleus (PVN) even under unstressful condition. This may reflect the important role of CRHR-2alpha in the autoregulation of CRH secretion in the PVN. To determine the regulation of CRHR-2alpha mRNA expression in the PVN, we examined the alteration of CRHR-2alpha mRNA levels in the PVN in rats with lipopolysaccharide (LPS) injection, corticosterone (CORT) administration or adrenalectomy and compared with that of CRHR-1 mRNA, using in situ hybridization histochemistry. I.p. LPS injection (50 microg) induced a significant increase in PVN CRHR-1 mRNA at 3 and 6 h whereas CORT administration (10 mg/day for 12 days) or adrenalectomy (sacrificed 7 days after surgery) decreased CRHR-1 mRNA levels in the PVN. These alterations in PVN CRHR-1 mRNA are consistent with previous reports. In contrast, CRHR-2alpha mRNA levels in the PVN were not altered by any of these treatments. These results indicate that CRHR-1 and CRHR-2alpha mRNA are differentially regulated in the PVN. Further study will be necessary to elucidate the CRHR-2alpha function in the PVN.