IN-VITRO REGULATION OF RAT SERTOLI-CELL INHIBIN MESSENGER-RNA LEVELS BY TRANSFORMING GROWTH-FACTOR-BETA-1 AND TUMOR-NECROSIS-FACTOR-ALPHA

In the present study, we examined the in vitro regulation of 20-day-ol d rat Sertoli cell inhibin alpha- and beta B-subunits mRNA levels by t ransforming growth factor-beta 1 (TGF-beta 1) and tumour necrosis fact or alpha (TNF alpha), two factors produced in the testis. Addition of TGF-beta 1 to highly purified cultured Sertoli cells resulted in a tim e- and dose-dependent enhancement in the alpha-subunit mRNA levels (ED (50)=2.4 pM; maximal increase of 2.6-fold after 48 h of treatment), wi thout affecting the beta B-subunit mRNA levels. Similarly, activin A u p-regulated the alpha- but did not modulate the beta B-subunit mRNA le vels. By contrast, TNF alpha decreased in a time- and dose-dependent f ashion the mRNA levels of the two inhibin subunits alpha and beta B (I C50=29 pM for both subunits; maximal decrease of 4.4- and of 4-fold af ter 72 and 24 h of treatment for respectively the alpha- and beta B-su bunits). The effects of TGF-beta 1 and TNF alpha on inhibin mRNA level s occurred within a dose range that might be expected under physiologi cal conditions. In addition, TGF-beta 1-treated Sertoli cells responde d to FSH or dibutyryl cyclic AMP ((Bu)(2)cAMP) by a further and signif icant additive increase of the alpha-subunit mRNA levels. TNF alpha-tr eated Sertoli cells responded significantly to FSH and to (Bu)(2)cAMP, thus attenuating the inhibitory action of TNF alpha on the alpha-inhi bin mRNA levels. Together, the present findings emphasize the ability of some local growth factors to modulate the effects of FSH on Sertoli cell function.