Evidence Suggesting that the Potentiating Action of Neuropeptide Y on Luteinizing Hormone (LH)‐Releasing Hormone‐Induced LH Release Remains Unaltered in Aged Female Rats

Abstract

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.

Alteration in Hypothalamic Neuropeptide Y (NPY) Secretion May Underlie Female Reproductive Ageing: Induction of Steroid‐Induced Luteinising Hormone Surge by NPY in Ovariectomised Aged Rats

“…It is therefore possible that the absence of increased NPY secretion in the afternoon of the LH surge may be responsible for the reported alteration in LHRH neuronal activity in MA regularly cycling rats (10–12, 48). Although the potentiating action of NPY on LHRH at the level of the pituitary is obligatory for the normal preovulatory LH surge in young rats (18, 49), this action of NPY on LHRH‐induced LH release remains unaltered in old constantly oestrous rats (42). These findings taken together suggest that a defect in the hypothalamic NPY neurosecretory mechanism, rather than an alteration in NPY action at the pituitary level, contributes to the reproductive senescence in female rats.…”

“…Young and MA rats showing regular 4‐day oestrous cycles were implanted stereotaxically with PPC (Plastics One, Roanoke, VA, USA) aimed at the ME‐ARC (Coordinates: anterior‐ posterior: 5.0 mm, lateral: 0.5 mm, vertical: 9.7 mm below the dura) and simultaneously OVX under pentobarbital anaesthesia (40 mg/kg, i.p.). Seven days later, rats were implanted s.c. with oestradiol‐17β (E 2 )‐filled (300 µg/ml sesame oil) Silastic capsules (10 mm/100 g body weight) as described previously (42). Forty‐eight hours later, rats received progesterone (2 mg/0.1 ml oil/300 g body weight) s.c. at 10.00 h and then connected to the PPC system at 11.00–11.30 h. Artificial cerebrospinal fluid (aCSF, 40) was perfused between 12.00 and 18.00 h at a flow rate of 20 µl/min.…”