Regulation of the differentiated functions of Leydig tumor cells by epidermal growth factor

Abstract

The three effects of mEGF on MA-10 Leydig tumor cells that have been discussed here are summarized in TABLE 7. The earliest effect of mEGF on MA-10 cells can be detected within 5 min of addition of mEGF and it lasts for about 60 min. During this time mEGF transiently attenuates hCG-stimulated adenylate cyclase activity. Although the magnitude of this effect is small, it can be correlated with a transient attenuation of the hCG-provoked increase in steroid synthesis. At longer times (i.e., 1-8 h) mEGF activates steroid synthesis by a "cAMP-independent pathway" and it potentiates (in a synergistic fashion) the activation of steroidogenesis by hCG, other compounds that activate adenylate cyclase activity, and cAMP analogues. At even longer times (i.e., 8-48 h) mEGF down-regulates the LH/CG receptors and by doing so, limits the steroidogenic response of the cells to hCG. From a biochemical point of view, our data provide an excellent example of those actions of growth factors that are unrelated to the control of cell multiplication, and of the complexity involved even when dealing with a single cell type and a single growth factor. Admittedly we know very little about the molecular basis of the phenomena described herein. Current work in our laboratory, however, is aimed at filling this gap. Among all the questions that we can address, we believe that it is particularly important to characterize the intracellular signaling system(s) activated by mEGF and to determine if a single signaling system is responsible for the diverse biological actions of mEGF in MA-10 cells. From a physiological point of view, our data may also prove important to the understanding of the regulation of testicular functions. There is increasing evidence for the production of EGF (or related peptides such as transforming growth factor alpha) in several tissues, including the testes and ovaries. These findings, together with the results summarized here suggest that EGF (or related peptides) act within the testes in a paracrine, or autocrine fashion and that they may have important modulatory effects on the activation of Leydig cell steroidogenesis by gonadotropins.