title: Effects of danazol and progesterone on sex hormone-binding globulin mRNA expression in human endometrial cancer cell line Ishikawa.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Gifu University School of Medicine, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Misao
authors.forename: Y
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: J
authors.initials: J
authors.lastname: Fujimoto
authors.forename: T
authors.initials: T
authors.lastname: Tamaya
mesh_terms: 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
chemical_list: D004965:Estrogen Antagonists; D012333:RNA, Messenger; D012738:Sex Hormone-Binding Globulin; D011374:Progesterone; D003613:Danazol