Revisiting the reproductive functions of neuropeptide Y

Neurons that produce neuropeptide Y have been implicated in the control of a variety of physiologic processes. This review specifically updates and reconsiders the large body of evidence supporting the idea that neuropeptide Y is also a key regulator of the reproductive hormone axis. Conventional pharmacologic approaches have been used in past studies to provide evidence that neuropeptide Y plays an important role in reproduction. In more recent investigations, however, gene-targeting approaches have also been used to re-examine these putative functions of neuropeptide Y. Pharmacologic studies of the reproductive effects of neuropeptide Y predicted that loss of the neuropeptide Y gene would cause an earlier initiation of puberty because of lack of inhibition of the hypothalamic-pituitary-gonadal axis, an increase in basal luteinizing hormone levels due to the loss of the inhibitory actions in a low steroid environment, a decrease in luteinizing hormone surge levels because of the absence of the facilitating effects of neuropeptide Y on proestrus, and consequent impairment of fertility. Surprisingly, only the anticipated diminution of the luteinizing hormone surge has been observed. The article discusses these findings and the limitations that apply to pharmacologic experiments, and interpretations of phenotypic changes that arise in genetically engineered mice.