Steroid receptor response elements

To determine the optimal concentrations of DHT and TBECH isoforms for AR activation, we stimulated HepG2 cells with DHT in a dose-dependent manner for 8 hr and with TBECH for 40 hr. Exposure to 50:50 TBECH-γδ resulted in a half-maximal effective concentration (EC 50 ) of nM ( R 2 = ), whereas exposure to 25:75 TBECH-γδ resulted in an EC 50 of nM ( R 2 = ; Figure 5 ). This suggests that TBECH-γ may be a better inducer of AR than TBECH-δ. Both of these diastereomers induce AR at concentrations that are comparable to those of DHT ( nM; R 2 = ) and indicate that these TBECH diastereomers are highly potent androgen agonists. Determination of AR activation by 50:50 TBECH-αβ demonstrated that these diastereomers are less potent, with an EC 50 of 174 nM ( R 2 = ), one order of magnitude higher than DHT or TBECH-γδ. The weakest inducer of AR was TBECH-β, with an EC 50 of 294 nM ( R 2 = ). We also observed that TBECH-γ and -δ are complete agonists to DHT, whereas TBECH-α and -β are partial agonists because they conferred only partial induction. Determination of relative induction by the different compounds showed a ± -fold induction after exposure to DHT, a ± -fold induction with 50:50 TBECH-γδ, a ± -fold induction with 25:75 TBECH-γδ, an ± -fold induction with TBECH-αβ, and a ± -fold induction with TBECH-β.

Steroid receptor response elements

steroid receptor response elements

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