Peptide-steroid interactions in brain regulation of pulsatile gonadotropin secretion

Reproductive function is regulated by an intricate system of peptide, steroid and amine factors interacting within the brain, pituitary and gonads. At no point is the complexity of the reproductive system better exemplified than in the exquisite interplay of factors required to produce and modulate pulsatile gonadotropin secretion. By extension, analysis of the pulsatile secretory pattern of the gonadotropins, as a means of assessing the contribution of these various factors, can reveal interactions too subtle to be detected by the conventional examination of mean gonadotropin concentration. Analysis of the pulsatile secretory patterns of both LH and FSH reveals striking differences between the two gonadotropins in their response to inhibitory, gonadal peptide and steroid factors, suggesting divergent paths of brain-pituitary regulation. Further studies to clarify this disparity in regulation have demonstrated that neutralization of endogenous LHRH completely abolishes pulsatile LH secretion without affecting pulsatile FSH secretion, suggesting the existence of another, as of yet unknown, brain factor which regulates FSH secretion. The feedback signals provided by gonadal steroids can induce both inhibition and facilitation of LHRH and LH secretion. Neurons of the central opiatergic system exert a tonic inhibitory influence on the catecholaminergic neurons regulating LHRH secretion, and are believed to mediate the inhibitory actions of the gonadal steroids on the LHRH system. Withdrawal of the gonadal steroids has been reported to cause a rapid loss of the tonic inhibitory control of the opiate system on LHRH secretion as revealed by a lack of response to naloxone. Reassessment of this system by analyzing the pulsatile pattern of LH secretion, however, reveals that the loss of naloxone effect after gonadectomy occurs very gradually and that an effect can still be obtained up to 2 weeks after the removal of gonadal steroids. These studies provide excellent examples of the complex interplay observed just between selected factors regulating pulsatile gonadotropin secretion. The use of pulsatile gonadotropin analysis is a powerful model, not only for providing greater clarity of known regulatory interactions, but also for revealing new and more subtle levels of control in the brain-pituitary-axis.