Effects of corticosterone on CRH mRNA and content in the bed nucleus of the stria terminalis; comparison with the effects in the central nucleus of the amygdala and the paraventricular nucleus of the hypothalamus

Abstract

We previously reported that corticosterone (CORT) increased corticotropin-releasing hormone (CRH) mRNA in the central nucleus of the amygdala (CEA), while reducing it in the paraventricular nucleus (PVN) of the hypothalamus by using in situ hybridization histochemistry. The bed nucleus of the stria terminalis (BNST) is closely related to the amygdala, and it is also a source of extrahypothalamic CRH; therefore, we examined CRH mRNA changes in the BNST following systemic treatment with CORT in adrenally-intact rats. Effects of adrenalectomy on CRH mRNA in the BNST, PVN and CEA were also examined. In addition, CRH content in these nuclei and in the median eminence (ME) were determined by micropunch dissection technique combined with CRH radioimmunoassay in CORT pellet implanted rats. Subcutaneous injections of high CORT (5 mg/day, over 14 days) increased CRH mRNA in the dorsal part of the lateral BNST (BSTLD) at 2, 4 and 8 days, although the low dose of CORT (1 mg/kg/day) had no significant effects. By contrast, in the ventral part of the BNST (BSTV) neither the high nor low dose of CORT altered CRH mRNA levels. In a second experiment, a slowly-releasing CORT pellet (200 mg, 60-day release) produced an elevation of CRH mRNA at both 1 and 2 weeks or at 1 week in the BSTLD or in the BSTV, respectively. These results show that glucocorticoids can facilitate CRH mRNA expression in the BSTLD in the same manner as seen in the CEA, and that CRH mRNA in the BSTLD can respond to CORT more than in the BSTV. In a third experiment, bilateral adrenalectomy, however, did not affect CRH mRNA in the BNST although there was a modest decrease in the CEA and a robust increase in the PVN. Finally, in CORT pellet (200 mg, for 2 weeks) implanted rats, CRH content in the ME significantly decreased and modestly increased in the CEA compared with control rats, whereas it did not change in the PVN and BNST. Taken together, these results suggest that (1) CRH in the BNST and the CEA may share some common functions in neuroendocrine and behavioral changes, but that (2) mechanisms of CRH synthesis or its releasing sites may be different in the BNST and CEA.