EFFECTS OF DANAZOL AND PROGESTERONE ON SEX HORMONE-BINDING GLOBULIN MESSENGER-RNA EXPRESSION IN HUMAN ENDOMETRIAL CANCER CELL-LINE ISHIKAWA

To ascertain one of the biological effects of danazol and progesterone on the uterine endometrial cancer cell line, Ishikawa, we investigate d 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-17 beta (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 i ts expression. The time course study showed the time-dependent decreas e of SHBG mRNA level by danazol and progesterone (10(-6) M) with or wi thout E2 (10(-8) M), except for a temporal increase by progesterone. T hese findings suggest that danazol and progesterone in a superphysiolo gical milieu down-regulate the intracellular SHBG-related steroidal ac tions, and that progesterone in a physiological milieu with estrogen u p-regulates it in a hormone-dependent cell Line. A decrease of intrace llular SHBG caused by high-dose danazol or progesterone might partly c ontribute to the abolition of the intracellular estrogen-dominant mili eu, and be related to the inhibition of estrogen-dependent growth of s ome endometrial cancer cells. (C) 1997 Elsevier Science Ltd.