INHIBITION OF AROMATASE-ACTIVITY IN RAT SERTOLI CELLS BY THYROID-HORMONE

Basal and FSH-induced aromatase activity in prepubertal rat Sertoli cells was inhibited by L-tri-iodothyronine (T-3) in a time- and dose-dependent manner. The effect was evident only after 6 h of preincubation with T-3 (10(-7) M) and the half-maximal dose was 0.5 +/- 0.2 nM, which correlated with the K-d of the nuclear T-3 receptor of rat Sertoli cells (K-d=1-2 nM). The effect was specific as judged by the lack of effect of the T-3 analogue 3-iodo-L-thyrosine. The inhibitory effect of T-3 was present over the entire range of FSH concentrations used (0.001-100 ng/ml). In T-3-treated Sertoli cells, aromatase activity induced by 8-bromo-cyclic AMP was inhibited by the same order of magnitude as that of FSH, thus suggesting that the inhibitory effect of T-3 was downstream from cyclic AMP formation. Furthermore, pretreatment of Sertoli cells cultures with T-3 (24h, 10(-7) M) did not affect basal or FSH-induced extracellular cyclic AMP accumulation. This effect of T-3 on rat Sertoli cell aromatase activity may be regarded as a part of the integrated mechanism by which thyroid hormone modulates the functions of the seminiferous epithelium.