INFLUENCE OF FOOD RESTRICTION ON NEUROPEPTIDE-Y, PROOPIOMELANOCORTIN,AND LUTEINIZING-HORMONE-RELEASING HORMONE GENE-EXPRESSION IN SHEEP HYPOTHALAMI

Chronic food restriction decreases secretion of 1,H as a result of inh ibitory influences on secretion of LHRH. We have previously reported t hat neuropeptide-Y (NPY) may directly or indirectly mediate this inhib itory effect on LHRH secretion. In the study reported here, we tested the hypothesis that long-term food restriction suppresses tonic releas e of LH as a result of 1) an increase in biosynthetic activity of NPY neurons in the arcuate nucleus of the hypothalamus, 2) an increase in activity of neurons that secrete beta-endorphin, and 3) a decrease in biosynthesis of LHRH. To test predictions of the hypothesis, we compar ed levels of mRNA encoding NPY, proopiomelanocortin (POMC; the precurs or peptide of beta-endorphin), and LHRH, as well as tonic secretion of LH in food-restricted and well-nourished ewe lambs. Ten ewe lambs wer e ovariectomized at 18 wk of age and randomly assigned to receive eith er 100% nutritional requirements (FED; n = 5), or 30% requirements (R; n = 5) between 18 and 25 wk of age. At 25 wk of age, blood samples we re taken every 10 min for 6 h and assayed for LH. The tonic release of LH in R lambs was less than that of FED lambs. Hypothalami were colle cted 4 days after blood sampling and sectioned at 12 mum for use in in situ hybridization. Radiolabeled molecular probes specific for mRNAs encoding NPY, POMC, or LHRH were hybridized to hypothalamic tissue sec tions. Levels of NPY mRNA were 88% greater in R vs. FED lambs (p < 0.0 1), whereas levels of POMC mRNA were 52% lower in R vs. FED lambs (p < 0.01). Mean cellular levels of mRNA encoding LHRH did not differ betw een R and FED lambs. Although the inhibitory effects of food restricti on on secretion of LH may be mediated by NPY, it is unlikely that beta -endorphin is a major inhibitory influence on LHRH neurons during unde rnutrition. Our results also provide further evidence that inhibition of LH secretion in food-restricted lambs does not involve decreased bi osynthesis of LHRH.