INCREASES IN NEUROPEPTIDE-Y CONTENT AND GENE-EXPRESSION IN THE HYPOTHALAMUS OF RATS TREATED WITH DEXAMETHASONE ARE PREVENTED BY INSULIN

The neurotransmitter neuropeptide Y (NPY) is abundant in the hypothala mus where its actions include the potent stimulation of food intake. T he peripheral metabolic and hormonal signals involved in its regulatio n are not clear. The aim of this study was to investigate possible act ions of corticosteroids and insulin on hypothalamic NPY synthesis and content in vivo. We measured NPY content in individual hypothalamic nu clei, and hypothalamic NPY mRNA by Northern blotting in whole hypothal amus in rats treated with dexamethasone (0.4 mg/kg/day) and dexamethas one plus insulin (60 U/kg/day), compared to controls. The effect of st opping dexamethasone treatment was also studied. Dexamethasone treatme nt produced significant increases in NPY in the paraventricular (11.0 +/- 1.3 vs. 7.1 +/- 0.4 fmol/mug protein, p < 0.05) and arcuate (6.2 /- 0.3 vs. 3.8 +/- 0.2 fmol/mug protein, p < 0.001) nuclei of the hypo thalamus, paralleled by a 38% increase in total hypothalamic NPY mRNA (p < 0.05). These changes were not seen in the group treated with dexa methasone plus insulin. In the group in whom dexamethasone was stopped , NPY mRNA was unchanged compared to controls, but peptide content rem ained increased in the arcuate but not the paraventricular nucleus (ar cuate 7.7 +/- 0.7 vs. 5.5 +/- 0.7, PVN 4.9 +/- 1.0 vs. 4.7 +/- 0.9 fmo l/mug protein). Thus hypothalamic NPY and its mRNA were increased by c orticosteroid administration, and this effect was prevented by systemi c insulin treatment. This dual regulatory system for hypothalamic NPY may be important in the control of food intake by corticosteroids and insulin.