Regulation of type-2 corticotropin-releasing hormone receptor mRNA in rat heart by glucocorticoids and urocortin

A novel subtype of corticotropin-releasing hormone (CRH) receptor, designated type-2 CRH receptor (CRHR-2), has been cloned by a number of laboratories, and its mRNA has been found to be distributed not only in the brain but in peripheral tissues such as heart and skeletal muscle. To date, however, the regulation of CRHR-2 mRNA is poorly understood. Therefore, we examined the effect of glucocorticoid treatment, adrenalectomy, and systemic administration of urocortin, a possible endogenous ligand for CRHR-2, on heart CRHR-2 mRNA levels in male Wistar rats, using in situ hybridization histochemistry. CRHR-2 mRNA in the heart was significantly decreased 9 h after systemic administration of urocortin (5 mu g/kg b.w.). Systemic administration of corticosterone (CORT; 10 mg/rat/day for 12 days) or CORT pellet (200 mg) implant for 7 and 14 days also decreased CRHR-2 mRNA in the heart, whereas it was unchanged 7 days after adrenalectomy. Thus, similar regulation of CRHR-2 mRNA in the rat heart by its ligand and glucocorticoids was observed. The precise mechanism of the regulation of CRHR-2 mRNA in the heart and the physiologic significance of cardiac CRHR-2 remains to be elucidated.