REGULATION OF NEUROPEPTIDE-Y AND ITS MESSENGER-RNA BY GLUCOCORTICOIDSIN THE RAT ADRENAL-GLAND

The effects of glucocorticoids on adrenal neuropeptide Y (NPY) and NPY mRNA levels have been investigated on adult male rats of the Wistar s train subcutaneously injected twice a day with dexamethasone (5 mg/day ), metyrapone (66 mg/day) or solvent (NaCl 0.9%) for 2.5 days and sacr ificed 2 h after the last injection. Dexamethasone induced a significa nt decrease in both the adrenal weight (30%) and the plasma corticoste rone concentration (85%) but a significant increase of the adrenal NPY content (about 25%) as well as of its mRNA (0.8 kb) (>100%), revealed by Northern blot analysis and by in situ hybridization. Dexamethasone was unable to affect significantly dopamine (DA), norepinephrine (NE) and epinephrine (E) content of the adrenals; in contrast, it induced a significant decrease (30%) of the plasma NE level. Metyrapone elicit ed a drop of the plasma corticosterone level (80%), but a rise (near 1 50%) of the plasma ACTH concentration associated with an increase (19% ) of the adrenal weight, a significant increase (30%) in the amount of adrenal NPY as well as a rise (>200%) of NPY mRNA content of the adre nal. Such treatment increased DA and NE (40%), and decreased E (>30%) content of the adrenals. Metyrapone-induced changes of catecholamine c oncentrations in the plasma were similar to that observed in the adren al gland. Data suggest that the increase in adrenal NPY mRNA content i nduced by dexamethasone is more likely due to humoral effect rather th an nervous effect of this synthetic glucocorticoid on the adrenal medu lla. A neural mechanism as splanchnic nerve activation in response to severe corticosterone deficiency is a reasonable hypothesis to explain the increase in adrenal NPY mRNA induced by metyrapone, although ther e are probably other, nonneural mechanisms by which metyrapone could s timulate adrenal NPY. Present data are consistent with glucocorticoid regulation of NPY gene expression and/or steady-state level of NPY mRN A in the adrenal gland.