PARACRINE REGULATION OF LEYDIG-CELLS

In addition to the endocrine control of Leydig cell functions by LH, p aracrine control of Leydig cell functions has been suspected from the indirect stimulatory effect of FSH on Leydig cells. Coculture experime nts of Leydig and Sertoli cells and the effect of Sertoli cell conditi oned media on Leydig cells confirmed the production by Sertoli cells o f acute steroideogenic factor(s) and factors involved in the positive or negative control of Leydig cell differenciated functions. Character ization and purification of these paracrine factors has been until rec ently unsuccessful. Another approach has been to investigate whether c ompounds of known biological activities in other systems, were produce d within the testis and act on leydig cells. IGF-I is produced by Sert oli and Leydig cells under the control of their respective gonadotropi n, LH and FSH. IGF-I enhanced hCG responsiveness of leydig cells by in creasing both LH receptor and steroidogenic enzymes. On the contrary T GF-beta which is also produced by Sertoli and Leydig cells is a potent inhibitor of Leydig cell functions. its production by Sertoli cells i s inhibited by FSH. Inhibin enhanced Leydig cell differentiated cell f unctions. Activin has, conversely to what has been published in the ra t, a stimulatory effect on Leydig cell functions in the immature porci ne Leydig cell model, The effects of these growth factors or related m olecules mainly consist in positive (IGF-I, Inhibin, Activin) or negat ive (TGF-beta, TGF-alpha/EGF bFGF) trophic effects regulating LH/hCG r eceptor number and mRNAs and steroidogenic enzyme mRNAs and activites, allowing regulation of the responsiveness of Leydig cells to LH. Thus both gonadotropins contribute, directly Sol LH and indirectly through paracrine mecanisms, for FSH, to testosterone production.