In vitro regulation of rat Sertoli cell inhibin messenger RNA levels by transforming growth factor-beta 1 and tumour necrosis factor alpha.

In the present study, we examined the in vitro regulation of 20-day-old rat Sertoli cell inhibin alpha- and beta B-subunits mRNA levels by transforming growth factor-beta 1 (TGF-beta 1) and tumour necrosis factor alpha (TNF alpha), two factors produced in the testis. Addition of TGF-beta 1 to highly purified cultured Sertoli cells resulted in a time- and dose-dependent enhancement in the alpha-subunit mRNA levels (ED50 = 2.4 pM; maximal increase of 2.6-fold after 48 h of treatment), without affecting the beta B-subunit mRNA levels. Similarly, activin A up-regulated the alpha- but did not modulate the beta B-subunit mRNA levels. By contrast, TNF alpha decreased in a time- and dose-dependent fashion the mRNA levels of the two inhibin subunits alpha and beta B (IC50 = 29 pM for both subunits; maximal decrease of 4.4- and of 4-fold after 72 and 24 h of treatment for respectively the alpha- and beta B-subunits). The effects of TGF-beta 1 and TNF alpha on inhibin mRNA levels occurred within a dose range that might be expected under physiological conditions. In addition, TGF-beta 1-treated Sertoli cells responded to FSH or dibutyryl cyclic AMP ((Bu)2cAMP) by a further and significant additive increase of the alpha-subunit mRNA levels. TNF alpha-treated Sertoli cells responded significantly to FSH and to (Bu)2cAMP, thus attenuating the inhibitory action of TNF alpha on the alpha-inhibin mRNA levels. Together, the present findings emphasize the ability of some local growth factors to modulate the effects of FSH on Sertoli cell function.