ALTERED EXPRESSION OF TYPE-2 CRH RECEPTOR MESSENGER-RNA IN THE VMH BYGLUCOCORTICOIDS AND STARVATION

In the rat, high-dose corticosterone (Cort) administration, the hyperc ortisolism of starvation, and adrenalectomy are all associated with de creased food intake and weight loss. We report here a study of the eff ects of high-dose Cort administration, starvation, and adrenalectomy o n two peripheral hormones known to influence food intake and energy us e, insulin and leptin. We also studied the impact of these interventio ns on the levels of type 2 corticotropin-releasing hormone receptor (C RHR-2) mRNA in the hypothalamic paraventricular nucleus (PVN) and vent romedial hypothalamus (VMH). The VMH is classically referred to as the satiety center because electrical stimulation of the VMH leads to inh ibition of food intake, whereas CRHR-8 are thought to transduce the pr ofound anorexogenic effects of CRH or its related peptide urocortin. S tarvation and adrenalectomy each lowered plasma insulin and leptin lev els and were associated with decrements in CRHR-8 mRNA levels in the V MH. Cort administration increased plasma leptin levels profoundly, as well as plasma insulin levels and the levels of VMH CRHR-8 mRNA. Under all experimental conditions, a positive correlation was seen between plasma leptin levels and VMH CRHR-2 mRNA. These data suggest that decr eased food intake and weight loss after high-dose Cort administration at least partially depend on the profound impact of Cort on plasma lep tin secretion in the rat; they suggest, moreover, an additional mechan ism for the satiety-inducing effects of leptin, namely increasing CRHR -8 in the VMH. The concordance of a fall in plasma insulin and leptin levels with the fall in VMH CRHR-8 mRNA levels further supports the id ea that compensatory responses during starvation and adrenalectomy inc lude not only the disinhibiting effects of reduced insulin and leptin levels on appetite through already-described mechanisms but also via a n effect of leptin on VMH CRHR-2. Neither Cort administration, starvat ion, nor adrenalectomy influenced the levels of CRHR-2 mRNA in the PVN , suggesting that these receptors are differentially regulated in diff erent hypothalamic regions.