CHRONIC ADMINISTRATION OF GLUCOCORTICOIDS DIRECTLY UP-REGULATES PREPRO-NEUROPEPTIDE-Y AND Y-1-RECEPTOR MESSENGER-RNA LEVELS IN THE ARCUATE NUCLEUS OF THE RAT

The complete sequence of the cDNA encoding the neuropeptide Y (NPY) Y- 1-receptor has recently been deduced from a rat brain library, and the presence of messenger ribonucleic acid (mRNA) encoding Y-1-receptor p rotein has been demonstrated within the brain. Using quantitative in s itu hybridization histochemistry, the content and distribution of Y-1- receptor and preproNPY mRNAs have been investigated in the hypothalami c arcuate nucleus of adrenalectomized rats receiving glucocorticoid re placement therapy for 12 days by means of either high doses of dexamet hasone in their drinking water or by subcutaneous corticosterone pelle ts. Basal metabolic parameters such as weight gain or loss, blood gluc ose and plasma insulin were monitored: Dexamethasone treatment induced weight loss and a state of hyperinsulinemia with normoglycemia, while corticosterone treated animals displayed metabolic parameters identic al to sham ADX animals. Within the arcuate nucleus of glucocorticoid t reated animals, levels of Y-1-receptor and preproNPY mRNAs were increa sed. In contrast, adrenalectomy itself had no effect upon Y-1-receptor mRNA levels or preproNPY mRNA levels in the arcuate nucleus. These st udies demonstrate that glucocorticoids exert a stimulatory action on l evels of Y-1-receptor mRNA and preproNPY mRNA levels in the hypothalam ic arcuate nucleus. This is the first evidence to suggest that the exp ression of a neuropeptide-receptor gene in the central nervous system may be directly sensitive to peripheral hormonal signals.