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

A large body of evidence suggests that a defect in the hypothalamic function may be the primary cause of reproductive ageing in female rats. We have previously shown that luteinising hormone (LH)-surge associated changes in hypothalamic neuropeptide Y (NPY) gene expression and median eminence (ME) NPY levels seen in young rats do not occur in middle-aged (MA) rats. The present study examined whether hypothalamic NPY release is altered during the steroid-induced LH surge in ovariectomised (OVX) MA rats, and whether exogenous NPY initiates steroid-induced LH surge in OVX old rats. In the first study, NPY release from the ME-arcuate nucleus, as assessed by the push-pull cannula technique, was significantly increased before and during the progesterone-induced LH surge in oestrogen (E-2)-primed ovariectomised young rats (2-3 months old). This antecedent increase in NPY release seen in young rats was not apparent in MA rats (11-13 months old) in association with a delayed and attenuated LH surge. In the second study, whereas progesterone failed to induce LH surges in E-2-primed ovariectomised old rats (23-25 months old), intracerebroventricular NPY (0.1-0.5 mu g) injections at 1100, 1200 and 13.00 h resulted in LH surge induction in E-2 + progesterone-primed ovariectomised old rats. Because increased hypothalamic NPY synthesis and release is obligatory for the preovulatory LH discharge in young rats, the present findings suggest that alteration in NPY release from the ME-arcuate nucleus contributes to the delayed and reduced LH surges in MA rats and may be involved in the subsequent loss of the LH surges in old rats.