Evidence suggesting that the potentiating action of neuropeptide Y on luteinizing hormone (LH)-releasing hormone-induced LH release remains unaltered in aged female rats.

Several lines of evidence suggest that one of the mechanisms by which the hypothalamic neuropeptide Y plays an obligatory role in the preovulatory luteinizing hormone (LH) discharge in young rats is to potentiate the action of LH-releasing hormone (LHRH) on LH release at the level of the pituitary. This study examined whether an alteration in the potentiating action of neuropeptide Y on LHRH-induced LH release may contribute to the attenuation or absence of LH surges during female reproductive ageing. Young regularly cycling (2-3-month-old) and old constant oestrous (19-20-month-old) rats ovariectomized for 7 days were primed with oestradiol-17beta-filled Silastic capsules. Two days later, rats received s.c. progesterone at 09.00 h and then were injected i.p. with either saline or pentobarbital at 13.30 hours. Pentobarbital-treated rats received i.v. pulses of neuropeptide Y, LHRH, a combination of neuropeptide Y and LHRH, or saline, every 30 min from 14.00 to 18.00 h via a jugular cannula. Hourly blood samples were collected between 11.00 and 21.00 h. In old rats, the progesterone-induced LH surge was significantly attenuated and delayed as compared to that of young rats. Pentobarbital injection completely blocked the LH surge. Neuropeptide Y pulses alone had no significant effect on LH release. In contrast, LHRH pulses increased LH release in both age groups, although the response was significantly reduced in older rats. While combined pulses of neuropeptide Y and LHRH significantly increased LH release in both young and old rats as compared to that of LHRH alone, the potentiating action of neuropeptide Y on LHRH-induced LH release remained unchanged between the two age groups. These results, together with our recent demonstration of altered hypothalamic neuropeptide Y neuronal activity in middle-aged pro-oestrous rats, suggest that a deficit in neuropeptide Y secretion and action in the hypothalamus, rather than a decrease in pituitary responsiveness to neuropeptide Y, may partially be responsible for the absence of LH surges in old rats.