NEUROPEPTIDE-Y Y-2 RECEPTORS HYPOTHALAMIC IN NEUROENDOCRINE AREAS AREUP-REGULATED BY ESTRADIOL AND DECREASED BY PROGESTERONE COTREATMENT IN THE OVARIECTOMIZED RAT

Central neuropeptide Y (NPY) systems are known to stimulate, via the Y -1 subtype of NPY receptor, the release of LHRH that leads to surges o f LH. Levels of NPY receptors in relation to the above modulation have not been assessed. This study, therefore, examined profiles of NPY re ceptors in ovariectomized (Ovx) rats and in Ovx rat treated with estra diol (E(2)) with or without cotreatment with progesterone (P-4). [I-12 5]Human PYY containing proline in position 34 [(Pro(34))hPYY] was used as the Y-1 receptor ligand, and [I-125]human peptide YY-(3-36) [hPYY- (3-36)] was used as the Y-2 site ligand. Treatment with E(2) over 3 da ys increased Y-2 binding in the preoptic hypothalamus and the medial b asal hypothalamus, whereas no changes were found in the lateral anteri or hypothalamus or the piriform cortex. Administration of P-4 (1.5 mg/ animal) on the third day of E(2) treatment reduced Y-2 binding in both the preoptic hypothalamus and the medial basal hypothalamus to or bel ow the density found in Ovx controls. The Y-1 receptor levels and the affinity of either Y-1 or Y-2 binding did not change appreciably with any of the treatments. No significant changes in the binding of wheat germ agglutinin were found at the time of the largest reduction in Y-2 receptor numbers by P-4, indicating the absence of a major membrane r eceptor reduction in response to the progestin. The down-regulation of Y-2 sites by P-4 preceded and accompanied the surge of serum LH induc ed by the progestin in E(2)-treated animals. A short term P-4 treatmen t thus appeals to reduce the Y-2 tone in hypothalamic areas involved i n LHRH secretion. This reduction might reinforce Y-1 drives known to s timulate the output of LHRH, and thus contribute to LH release.