EVIDENCE THAT HEPARIN-BINDING AUTOCRINE FACTORS MODULATE TESTOSTERONEPRODUCTION BY THE ADULT-RAT LEYDIG-CELL

Androgen production by adult rat Leydig cells is stimulated by pituita ry LH but can also be modulated in vitro by paracrine stimulatory and inhibitory factors, many of which belong to growth factor families, Th eir actions are mediated tl?rough cell surface or extracellular matrix proteoglycans and the aim of this study was to determine the role of cell surface heparan sulfate proteoglycans in the regulation of testos terone secretion by adult rat Leydig cells. The presence of sodium chl orate (25 mM) and protamine sulfate (10 mu g/ml) inhibited testosteron e production by LII stimulated cells by over 50%, but had no effect on unstimulated cells. The LH responsiveness and testosterone production returned to normal after these agents were removed from the culture m edia. No significant difference in LH receptor numbers al the end of t he culture period was seen between sodium chlorate treated and untreat ed cells. Testosterone production by dibutryl-cAMP stimulated Leydig c ells was also inhibited by sodium chlorate. The addition of heparin in hibited testosterone production by LH stimulated cells in a dose-depen dent manner, however, in unstimulated Leydig cells heparin stimulated testosterone production to up to 50% of that seen in LH stimulated cel ls. These data suggest that cell surface heparan sulfate proteoglycans modulate testosterone production by adult Leydig cells in vitro, and that this may involve the autocrine actions of heparin binding growth factors on the Leydig cells.