A TIME-COURSE STUDY ON THE IN-VITRO EFFECTS OF T-3 AND TESTOSTERONE ON ANDROGEN AND ESTROGEN-RECEPTORS IN PERIPUBERAL PRIMARY RAT SERTOLI CELLS

The effect of Tri-iodothyronine (T-3) administration leading to the pr ecocius differentiation of Sertoli cell in prepuberal rats has been pr eviously shown. The functional maturation of Sertoli cells is associat ed with changes in androgen metabolism. We have recently demonstrated that T-3 influences androgen metabolism in Sertoli cells by inhibiting aromatase activity and reduces drastically the ER contents in peripub ertal hypothyroid rats. To better understand the role of Tg in modulat ing steroid action on Sertoli cells, we performed a time course study evaluating the in vitro effects of T-3 and testosterone (T) on androge n (ARs) and estrogen (ERs) receptor content in Sertoli cells isolated from two weeks old Wistar rats. ARs and ERs basal levels did not chang e during the time course study indicating that the exposure to culture medium per se did not affect either receptor type. After 24 hrs of in cubation with either T-3 or T, a decrease of ERs in both nucleus and c ytosol was observed. Such a decrease was augmented by the simultaneous administration of both hormones. ARs displayed a different temporal p attern in the two cellular compartments and exhibited an earlier rise in the cytosol induced by either T-3 or T. At 36 hrs, ARs were signifi cantly enhanced in both compartments in response to either T or T-3 ex posure while combined hormonal treatment caused an additive increase c ompared with the single treatment group. As a consequence of the oppos ite behaviour pattern displayed by ARs and ERs, the ratio between tota l ARs and ERs contents was increased after 24 hrs of exposure to hormo nal treatment. To evaluate if treatments performed induced a functiona l maturation of Sertoli cells, transferrin levels in culture medium we re measured. The increase of this protein paralleled that of ARs conte nt as well as that of ARs/ERs ratio. This study demonstrates that thyr oid hormone induces a progressive increase of (AR)/(ER) ratio in the d ifferentiating Sertoli cells bringing them to a prevalent androgen dep endency along their functional maturation.