In the present study, we examined the in vitro regulation of 20-day-old rat Sertoli cell inhibin α- and βB-subunits mRNA levels by transforming growth factor-β1 (TGF-β1) and tumour necrosis factor α (TNFα), two factors produced in the testis. Addition of TGF-β1 to highly purified cultured Sertoli cells resulted in a time- and dose-dependent enhancement in the α-subunit mRNA levels (ED50=2·4 pm; maximal increase of 2·6-fold after 48 h of treatment), without affecting the βB-subunit mRNA levels. Similarly, activin A up-regulated the α-but did not modulate the βB-subunit mRNA levels. By contrast, TNFα decreased in a time- and dose-dependent fashion the mRNA levels of the two inhibin subunits α and βB (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 α- and βB-subunits). The effects of TGF-β1 and TNFα on inhibin mRNA levels occurred within a dose range that might be expected under physiological conditions. In addition, TGF-β1-treated Sertoli cells responded to FSH or dibutyryl cyclic AMP ((Bu)2cAMP) by a further and significant additive increase of the α-subunit mRNA levels. TNFα-treated Sertoli cells responded significantly to FSH and to (Bu)2cAMP, thus attenuating the inhibitory action of TNFα on the α-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.
Journal of Endocrinology (1995) 146, 501–508