Induction of estrogen receptor-alpha and -beta activities by synthetic progestins.
The cellular action of steroid hormones is mediated by specific receptors. Recently, two different estrogen receptors (ER), alpha and beta, have been cloned with a specific tissue distribution. Active estrogen as well as active progestin are compounds of oral hormonal contraceptives and hormone replacement therapy. To examine the regulation of ER-alpha and -beta activities after treatment with synthetic progestins and synthetic and natural estrogens, COS 7 cells were transfected with the vector expressing ER-alpha and -beta in combination with a luciferase reporter vector. ER-alpha activity was upregulated in the presence of synthetic progestins in a dose-dependent manner. Norethisterone, norethynodrel and desogestrel proved to be the most potent stimulatory agents of ER-alpha expression. On the other hand, not all progestins exhibited a stimulatory action on ER-beta activity. Only norgestrel, levonorgestrel, norethynodrel and norethisterone induced ER-beta-activating functions in a dose-dependent manner. Luciferase activity due to estrogen stimulation served as a positive control. Our results indicate that progestins have different effects on the activities of ER-alpha and -beta.
Rabe
T
T
Department of Obstetrics and Gynecology, Ruprechts-Karls-Universitaet, Heidelberg, Germany.
Bohlmann
M K
MK
Rehberger-Schneider
S
S
Prifti
S
S
D000818:Animals; D019556:COS Cells; D017135:Desogestrel / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004997:Ethinyl Estradiol / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D009640:Norethindrone / Q000494:pharmacology; D009641:Norethynodrel / Q000494:pharmacology; D045167:Progesterone Congeners / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000235:genetics; D014162:Transfection
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D045167:Progesterone Congeners; D011960:Receptors, Estrogen; D004997:Ethinyl Estradiol; D004958:Estradiol; D017135:Desogestrel; D009641:Norethynodrel; D008156:Luciferases; D009640:Norethindrone