Ageing of the neuropeptidergic signals in rats.

With advancing age, subtle and progressive disintegration of several components of peptidergic signals that drive luteinizing-hormone-releasing hormone (LHRH) secretion contribute to diminished pituitary-gonadal function in both sexes of the rat. The results show that in female rats, ageing per se and unopposed exposure to oestrogen disrupt different loci in the transmission line to neurones that release LHRH. Ageing per se appears to abolish the restraint on the influence of inhibitory opioids induced by a neural clock--an event necessary for the preovulatory surge of luteinizing hormone to occur in young rats. By contrast, unopposed exposure to oestrogen disrupts the progression and transduction of information at hypothalamic loci downstream from the neural clock-opioid link. In male rats, the age-related diminution in pituitary-gonadal function is probably due to a gradual decrease in release of neuropeptide Y, an excitatory peptidergic signal to LHRH-expressing neurones. Further studies have revealed that this decline is a consequence of age-related acquisition of refractoriness to testosterone by neurones producing neuropeptide Y. Cumulatively, these findings underscore the key roles of hypothalamic peptidergic signals to LHRH-expressing neurones in the ageing process of the reproductive system in rats.