An active and selective molecular mechanism mediating the uptake of sex steroids by prostate cancer cells

Steroid hormones play important roles in normal physiological functions and diseases. Sex steroids hormones are important in the biology and treatment of sex hormone-related cancer such as prostate cancer and breast cancer. Cells may take up steroids using multiple mechanisms. The conventionally accepted hypothesis that steroids cross cell membrane through passive diffusion has not been tested rigorously. Experimental data suggested that cells may take up sex steroid using an active uptake mechanism. 3H-testosterone uptake by prostate cancer cells showed typical transporter-mediated uptake kinetic. Cells retained testosterone taken up from the medium. The uptake of testosterone was selective for certain steroid hormones but not others. Data also indicated that the active and selective uptake mechanism resided in cholesterol-rich membrane domains, and may involve ATP and membrane transporters. In summary, the present study provided strong evidence to support the existence of an active and selective molecular mechanism for sex steroid uptake. •Testosterone (T) uptake was mediated by a selective and active mechanism.•The uptake mechanism could be blocked by progesterone (P4) and estradiol (E2).•The uptake of P4 and E2 was mediated by mechanisms different from T uptake.•The uptake mechanisms were located in cholesterol-rich cell membrane domains.