Nonsteroidal signals originating in the gonads.

The discovery of the various peptide factors in the gonads followed different paths. A number of factors were specifically searched for because of physiological experiments that predicted that an activity from the gonads was necessary to explain phenomena. Such was the case for gonadal steroids and for such peptide factors as inhibin, MIS, OMI, FRP, seminal plasma inhibin, relaxin, PA factor and other proteases, and ABP. In the process other factors such as activin and follistatin were serendipitously discovered. A second group of factors was discovered because in vitro experiments of various combinations of gonadal cell types failed to replicate in vivo findings, suggesting missing signals. Such substances are the panoply of growth factors aiding in differentiation and growth promotion and inhibition: LS and LI, P-Mod-S, clusterin, and various components of the ECM. Finally, and most recently, another set of peptides has been identified because immunological or molecular probes have been used to search gonadal tissue for factors originally discovered elsewhere; these include POMC, GnRH-like peptide, oxytocin, AVP, angiotensin, ANF, CRF, neural peptides, and c-mos. Our understanding of the relationship of most of these peptides to the local signals necessary for gonadal function is still very elementary. Clearly some like relaxin and inhibin function as important hormones, and ABP, for example, probably functions importantly in transporting testosterone down the tubule. Most local paracrine or autocrine peptide signals appear to act in relationship to gonadotropin levels probably in local differentiation in the process of gamete maturation, but this is only conjecture at this point. No experimental verification that any of these factors is involved in follicle selection for recruitment or for atresia is yet available. For many of the factors local receptors have not yet been identified. The richness of the variety of peptides in the gonads suggests that microanalysis of cell-cell signaling would be rewarding, but at the time of this writing such investigations are not yet possible.