STEROID MODULATION OF NEUROPEPTIDE Y-INDUCED LUTEINIZING-HORMONE-RELEASING HORMONE-RELEASE FROM MEDIAN-EMINENCE FRAGMENTS FROM MALE-RATS

Neuropeptide Y (NPY) has been shown to stimulate hypothalamic release of luteinizing hormone-releasing hormone (LHRH) both in vitro and in v ivo. In Median eminence female rats, NPY facilitation of LHRH release is greatly augmented in Gonadal steroids advance of preovulatory LHRH surges, likely via the actions of ovarian steroids. However, the role of NPY in regulating LHRH release in male rats and the effects of test icular hormones on LHRH responses to NPY in males are not well underst ood. The objective of the present studies was to determine whether NPY stimulates LHRH release in vitro from hypothalamic tissue of male rat s, and whether these effects could be modulated by testosterone (T). M ediobasal hypothalamic (MBH) or median eminence (ME) fragments from ei ther sham-operated or castrated male rats (7 days) were placed in supe rfusion chambers and superfused with M199 for a 30-min baseline, 30-mi n challenge with NPY (10(-7) M), and a final 30-min challenge with 56 mM KCl. One-milliliter fractions were collected every 10 min and avera ge LHRH release values over the 30-min periods were compared among gro ups. NPY (10(-7) M) produced a significant increase in LHRH release fr om the MBH and ME from intact animals. In contrast, the same dose of N PY did not stimulate LHRH release from tissues from castrated animals; only with a higher dose of NPY (10(-6) M) were the effects of NPY on LHRH release significant. Potassium challenge (56 mM KCl) significantl y stimulated LHRH release from the ME of both intact and castrate male rats suggesting that all tissues were able to respond to a stimulus, and that castration did not alter the responsiveness of the LHRH neuro n to a nonspecific secretagogue. To determine the extent to which T re gulates the sensitivity of LHRH responses to NPY, male rats were castr ated and implanted with T capsules that maintained either low (1.24 +/ - 0.06 ng/ml) or high (2.17 +/- 0.31 ng/ml) physiological plasma level s of T. Treatment with the higher dose of T restored the ability of NP Y to stimulate LHRH release from the ME tissues. These results demonst rate that NPY stimulates LHRH release from the hypothalamus in vitro, and that gonadal steroids, in this case T and/or its metabolites, modu late the responsiveness of the LHRH neuron to NPY. Based on these data from intact and castrate-derived tissues, it appears that steroids ar e necessary to maintain LHRH responsiveness to NPY receptor stimulatio n.