title: Induction of androgen receptor activity by norgestimate and norelgestromin in MDA-MB 231 breast cancer cells.
abstract: The function and clinical significance of the androgen receptor (AR) in human breast cancer are still not clear. The synthetic progestins, norgestimate and norelgestromin, were designed to minimize the adverse effects such as acne, hirsuitism and metabolic changes observed with older oral contraceptives while maintaining contraceptive effectiveness and cycle control. AR-mediated effects of these synthetic progestins were studied in an in vitro transactivation assay, employing DNA co-transfection of an AR expression vector and luciferase reporter gene construct in the MDA-MB 231 human breast cancer cell line. Testosterone acetate and 5alpha-dihydrotestosterone induced the reporter gene transcription, whereas incubation of the transfected cells with the natural progestin 17alpha-hydroxyprogesterone did not markedly induce luciferase activity. The progestins norgestimate and norelgestromin exerted a very low androgenic activity. Our data suggest that norgestimate and its metabolite norelgestromin possess weak androgen-like properties. The use of these compounds for clinical application may be of great advantage in the treatment of breast cancer as well as hyperandrogenism in women.
authors.affiliation: Department of Obstetrics and Gynecology, Women's Hospital, University of Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Prifti
authors.forename: I
authors.initials: I
authors.lastname: Lelle
authors.forename: T
authors.initials: T
authors.lastname: Strowitzki
authors.forename: T
authors.initials: T
authors.lastname: Rabe
mesh_terms: D019326:17-alpha-Hydroxyprogesterone / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism*; D003277:Contraceptives, Oral, Combined / Q000494:pharmacology*; D013196:Dihydrotestosterone / Q000494:pharmacology; D004338:Drug Combinations; D005003:Ethisterone / Q000031:analogs & derivatives; D005822:Genetic Vectors; D006801:Humans; D008156:Luciferases / Q000235:genetics; D009644:Norgestrel / Q000031:analogs & derivatives* / Q000494:pharmacology*; D010091:Oximes; D011944:Receptors, Androgen / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D013739:Testosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; D010091:Oximes; D011944:Receptors, Androgen; D013196:Dihydrotestosterone; D009644:Norgestrel; D013739:Testosterone; C040594:testosterone acetate; D019326:17-alpha-Hydroxyprogesterone; C017576:norgestimate; D008156:Luciferases; D005003:Ethisterone; C449219:norelgestromin