The neuropeptide luteinizing hormone-releasing hormone (LHRH) is the prime regulator of gonadal function in vertebrates. Studies on the distribution of neurons containing pro-LHRH peptides have provided very useful information about the anatomical and functional arrangement of the LHRH network. Additional studies evaluating the expression, distribution and secretion of pro-LHRH peptides indicated that gonadal steroids can profoundly affect these parameters and thereby influence the overall activity of LHRH neurons. We also presented direct evidence that the LHRH neuronal system can """"""""auto-regulate"""""""" its own activity, providing a functional correlate to the anatomical studies describing recurrent axon collaterals in LHRH neurons. This auto-regulatory mechanism may play a key role in determining a coordinated pulsatile or rhythmic LHRH neuronal activity. Using an in vitro system developed in our laboratory, we have performed an extensive characterization of the major neurotransmitters (norepinephrine, dopamine opioid peptides, GABA, etc.) regulating LHRH secretion, and of important internal (gonadal steroids and peptides, lactation, etc.) and environmental (stress, neurotoxins) factors affecting the interaction between neurotransmitters and the LHRH neurons. In many cases, these in vitro studies were conducted in parallel with in vivo paradigms, to obtain a direct estimation of changes in LHRH secretion and function in vivo. Steroids play a major role in maintaining the secretory capacity of the LHRH neuron, an effect which appears to be mediated by interneurons rather than by direct actions at the LHRH neuron. The in vitro model allowed us to characterize the role of CA2+, arachidonate metabolites (PGE2 and different lipoxygenase metabolites) and protein kinase C activation on the regulation of pro-LHRH peptide(s) secretion from nerve terminals. These studies should advance our understanding of the complex interactions between central neurotransmitter systems and internal or external environmental factors influencing reproductive functions.
