Neuropeptide Y Y2 receptors in hypothalamic neuroendocrine areas are up-regulated by estradiol and decreased by progesterone cotreatment in the ovariectomized rat.

Central neuropeptide Y (NPY) systems are known to stimulate, via the Y1 subtype of NPY receptor, the release of LHRH that leads to surges of LH. Levels of NPY receptors in relation to the above modulation have not been assessed. This study, therefore, examined profiles of NPY receptors in ovariectomized (Ovx) rats and in Ovx rat treated with estradiol (E2) with or without cotreatment with progesterone (P4). [125I]Human PYY containing proline in position 34 [(Pro 34 )hPYY] was used as the Y1 receptor ligand, and [125 I]human peptide YY-(3-36) [hPYY-(3-36)] was used as the Y2 site ligand. Treatment with E2 over 3 days increased Y2 binding in the preoptic hypothalamus and the medial basal hypothalamus, whereas no changes were found in the lateral anterior hypothalamus or the piriform cortex. Administration of P4 (1.5 mg/animal) on the third day of E2 treatment reduced Y2 binding in both the preoptic hypothalamus and the medial basal hypothalamus to or below the density found in Ovx controls. The Y1 receptor levels and the affinity of either Y1 or Y2 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 Y2 receptor numbers by P4, indicating the absence of a major membrane receptor reduction in response to the progestin. The down-regulation of Y2 sites by P4 preceded and accompanied the surge of serum LH induced by the progestin in E2-treated animals. A short term P4 treatment thus appears to reduce the Y2 tone in hypothalamic areas involved in LHRH secretion. This reduction might reinforce Y1 drives known to stimulate the output of LHRH, and thus contribute to LH release.