Abstract

Food restricted lactating rats show a prolonged period of lactational infertility. Previous studies suggest that at least part of this effect is due to prolonged suppression of pulsatile release of luteinizing hormone (LH) that results from the combined effects of high circulating levels of progesterone and some, as yet unidentified, neurohormone. There is converging evidence to suggest that Neuropeptide Y (NPY) acting through its Y5 receptor subtype inhibits the reproductive axis. The hypothesis that Y5 receptor activation prolongs lactational infertility was tested in Experiment 1. In Experiment 2, the combined effects of Y5 receptor inactivation and administration of the progesterone receptor blocker RU486 were investigated. In both experiments production of the Y5 receptor was blocked by administration of antisense oligodeoxynucleotides (ODNs) targeted to the Y5 receptor from days 13-20 postpartum to food restricted (FR) dams. Vehicle-, scrambled ODN- treated FR and ad libitum (AL) fed dams served as controls. In Experiment 2, Y5 antisense and scrambled ODNs were co-administered with RU486 (5mg/kg). Length of lactational diestrous was significantly shorter in FR dams treated with Y5 antisense ODNs than any other FR groups. Maternal weight gain and pup growth was also reduced in Y5 antisense ODN treated dams. All females treated with RU486 displayed a length of lactational infertility similar to that seen in AL dams. Together these results suggest that both progesterone and Y5 receptor inactivation is effective in reducing the length of lactational anovulation, although whether they have direct effects on LH secretion remains to be determined.