The present study investigated the role of hypothalamic VIP in the regulation of the LH and PRL surge using immunoneutralization of endogenous VIP in mature ovariectomized (OVX), estradiol benzoate (EB)-treated female Wistar rats. We compared the effect of intracerebroventricular (i.c.v.) injections of a VIP antiserum (VIP-Ab) with that of saline (Ctr) on LH and PRL profiles in two separate groups of rats following two subcutaneous EB injections on days 8 and 9 after OVX. VIP-Ab or Ctr injections were given during the second half of the dark period, i.e. at 22:00 h (day 9), and, in addition, the following morning, i.e. at 08:00 h (day 10), just before the expected onset of the LH surge. Hourly blood samples were collected between 09:00 and 18:00 h on day 10. In addition, we studied the reproducibility of EB-induced LH and PRL surges and compared the effect of Ctr and VIP-Ab treatment on sequential surges in individual OVX females, i.e. 10 and 23 days after OVX, using each animal as its own control. Although we observeda large variation in the height and timing of LH and PRL peak levels between EB-treated females, the characteristics of successive surges of individual rats were highly reproducible. This reproducibility suggests that differences in functioning of the suprachiasmatic nucleus as well as in the response of the hypothalamus to steroid feedback largely explain the normal variation in hormone responses between rats. The VIP-Ab treatment resulted in a significant delay in the time course and a strong reduction of the magnitude of the afternoon LH and PRL surge. When analyzed within individual females, the effect of VIP-Ab treatment was even more pronounced due to a reduction in variability when each animal was used as its own control. These results suggest that hypothalamic VIP is an important regulator of both the timing and the magnitude of the EB-induced LH and PRL surge in the OVX rat, and suggest that its role may be stimulatory in this respect.
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