The Effect of Vasoactive Intestinal Peptide on the Rat Ovary

Abstract

In recent years, the localization and physiological significance of vasoactive intestinal peptide (VIP) in various organs have been studied. Investigations of the significance of VIP in the ovary have been done, but the detailed mechanism of action is still unknown. We made in vitro studies of VIP using rat ovaries. Ovarian granulosa cells were collected after treatment with estrogen in immature hypophysectomized rats. Luteal cells were collected from immature rats treated with pregnant mare serum (PMS) and human chorionic gonadotropin (hCG). These cells were cultured in a serum free medium for 48 hr in the absence or presence of various amounts of VIP. We determined the amount of steroids produced in the culture medium by specific RIA. Activities of 3 beta-HSD in the granulosa cells were determined by the amount of progesterone formed from labelled pregnenolone. Induction of LH-receptor in the granulosa cells by VIP and VIP-receptor in these cells was investigated. VIP stimulated estrogen and progesterone production dose and time dependently with an approximate ED50 value of 3 x 10(-8) M. The amount of cyclic adenosine monophosphate (c-AMP) was similarly increased. VIP enhanced 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) activity when incubated with the granulosa cells for 24 hours. VIP stimulated the granulosa cells in a way similar to follicle stimulating hormone (FSH), but the stimulating effect was slightly less than that of FSH. Unlike FSH, VIP did not induce LH-receptor. The binding of 125I-VIP with the granulosa cells was blocked, dose dependently, by unlabelled VIP, suggesting the presence of VIP-receptor in the granulosa cells. Another peptide, PHM-27, stimulated the granulosa cells although its potency was less than that of VIP. In contrast, gastrin, CCK and secretion did not stimulate the granulosa cells at all. According to the present study. VIP did not exert any effect on the luteal cells, and progesterone production in vitro was not stimulated by this peptide. The VIP effects seem to be at least partly c-AMP dependent and may be mediated through the VIP-receptor in the granulosa cells. The observed direct effects of VIP suggest that it may act as a local hormone to regulate the ovarian function.