To ascertain one of the biological effects of danazol and progesterone on the uterine endometrial cancer cell line, Ishikawa, we investigated the effects of these steroids on sex hormone-binding globulin (SHBG) mRNA expression by competitive reverse transcription-polymerase chain reaction-Southern blot analysis (RT-PCR-SBA). Estradiol-17beta (E2) in any concentration given did not exert any significant effect on the expression of SHBG mRNA. Danazol and progesterone significantly (P < 0.05) suppressed the expression of SHBG mRNA dose-dependently starting at a concentration of 10(-6) and 10(-8) M, respectively. Progesterone, in a low concentration (10[-10] M) with E2 (10[-8] M), significantly (P < 0.05) increased the expression of SHBG mRNA, but danazol did not. In contrast, danazol and progesterone in high concentrations (10[-6] to 10[-5] M) with E2 (10[-8] M) significantly (P < 0.05) suppressed its expression. The time course study showed the time-dependent decrease of SHBG mRNA level by danazol and progesterone (10[-6] M) with or without E2 (10[-8] M), except for a temporal increase by progesterone. These findings suggest that danazol and progesterone in a superphysiological milieu down-regulate the intracellular SHBG-related steroidal actions, and that progesterone in a physiological milieu with estrogen up-regulates it in a hormone-dependent cell line. A decrease of intracellular SHBG caused by high-dose danazol or progesterone might partly contribute to the abolition of the intracellular estrogen-dominant milieu, and be related to the inhibition of estrogen-dependent growth of some endometrial cancer cells.