CORTICOSTERONE INHIBITS UNCOUPLING PROTEIN GENE-EXPRESSION IN BROWN ADIPOSE-TISSUE

Uncoupling protein (UCP) mRNA levels were studied in the interscapular brown adipose tissue (BAT) of rats undergoing different manipulations of the adrenal function and BAT adrenergic stimulation. Adrenalectomy did not affect UCP mRNA levels for up to 8 days postsurgery. However, adrenalectomized rats underwent a greater increase in UCP mRNA levels (26%) than intact rats after 4 h of cold exposure. Administration of corticosterone (500 mug. 100 g body wt-1.day-1 sc) to intact or adrenalectomized rats, kept at 28-degrees-C, produced a marked decrease of UCP mitochondrial content and cellular mRNA levels in a time-dependent manner (30% by 12 h and 50% by 24 h). Pretreatment of intact rats with corticosterone virtually abolished the UCP mRNA response to cold and norepinephrine (NE). In contrast, when rats had been preexposed to cold for 96 h, the injection of corticosterone did not affect UCP mRNA. These results show that corticosterone is a powerful inhibitor of UCP gene expression in vivo. Corticosterone inhibits both basal gene expression at thermoneutrality and the response to adrenergic stimulation either by cold or exogenous NE, suggesting a direct action on BAT. The data further suggest that corticosterone inhibits the initial accumulation of UCP mRNA mediated by UCP gene transcription, rather than accelerating the degradation of UCP mRNA.