Regulation of neuropeptide Y and its mRNA by glucocorticoids in 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 strain subcutaneously injected twice a day with dexamethasone (5 mg/day), metyrapone (66 mg/day) or solvent (NaCl 0.9%) for 2.5 days and sacrificed 2 h after the last injection. Dexamethasone induced a significant decrease in both the adrenal weight (30%) and the plasma corticosterone 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 elicited a drop of the plasma corticosterone level (80%), but a rise (near 150%) 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 adrenal. Such treatment increased DA and NE (40%), and decreased E (>30%) content of the adrenals. Metyrapone-induced changes of catecholamine concentrations in the plasma were similar to that observed in the adrenal gland. Data suggest that the increase in adrenal NPY mRNA content induced by dexamethasone is more likely due to humoral effect rather than nervous effect of this synthetic glucocorticoid on the adrenal medulla. 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 there are probably other, nonneural mechanisms by which metyrapone could stimulate adrenal NPY. Present data are consistent with glucocorticoid regulation of NPY gene expression and/or steady-state level of NPY mRNA in the adrenal gland.