Acute increase in responsiveness of luteinizing hormone (LH)-releasing hormone nerve terminals to neuropeptide-Y stimulation before the preovulatory LH surge.

Abstract

Neuropeptide-Y (NPY) neurons regulate LH secretion in part through facilitation of LHRH release. We tested the hypothesis that responsiveness of LHRH neurons to NPY's facilitatory actions is physiologically regulated during the estrous cycle, and specifically, that it may be increased as a component of the gonadotropin surge-generating process. A dynamic superfusion paradigm was used to examine the role of cycle stage and time of day on LHRH responsiveness to NPY stimulation, using median eminence tissue from animals killed at 0900, 1400, and 1800 h on metestrus and proestrus. Tissue obtained at 0900 and 1800 h on metestrus did not exhibit significant LHRH responses to 10(-7) M NPY, and only moderate responses were seen at 1400 h on metestrus and 0900 h on proestrus. At 1400 h on proestrus, however, median eminence responsiveness to the same concentration of NPY was significantly increased, with LHRH responses to NPY being 2- to 5-fold greater than those at 0900 (P < 0.01), 1400 (P < 0.05), and 1800 h on metestrus (P < 0.01) and at 0900 h on proestrus (P < 0.05). Neither cycle-related changes in basal LHRH release nor changes in the releasability of LHRH in response to depolarization could account for the accentuated responses in the 1400 h proestrous group. These data clearly demonstrate that the responsiveness of LHRH terminals and/or their afferents to the actions of NPY is acutely enhanced during a brief window of time on proestrus, viz. immediately before generation of gonadotropin surges. Our findings are consistent with the hypothesis that the preovulatory endocrine milieu permits an acute increase in the responsiveness of LHRH nerve terminals to the actions of NPY, perhaps by prompting increases in the number and/or affinity of NPY receptors.