Effects of danazol and progesterone on sex hormone-binding globulin mRNA 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 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.
Misao
R
R
Department of Obstetrics and Gynecology, Gifu University School of Medicine, Japan.
Nakanishi
Y
Y
Fujimoto
J
J
Tamaya
T
T
D000230:Adenocarcinoma / Q000235:genetics; D003613:Danazol / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000235:genetics; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D016133:Polymerase Chain Reaction; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D012738:Sex Hormone-Binding Globulin / Q000187:drug effects* / Q000235:genetics; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured / Q000187:drug effects; D015854:Up-Regulation
D004965:Estrogen Antagonists; D012333:RNA, Messenger; D012738:Sex Hormone-Binding Globulin; D011374:Progesterone; D003613:Danazol