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 acti ve progestin are compounds of oral hormonal contraceptives and hormone repl acement therapy. To examinate the regulation of ER-alpha and -beta activities after treatmen t with synthetic progestins and synthetic and natural estrogens, COS 7 cell s were transfected with the vector expressing ER-alpha and -beta in combina tion with a luciferase reporter vector. ER-alpha activity was upregulated i n the presence of synthetic progestins in a dose-dependent manner. Norethis terone, norethynodrel and desogestrel proved to be the most potent stimulat ory agents of ER-alpha expression. On the other hand, nor all progestins ex hibited a stimulatory action an ER-beta activity. Only norgestrel, levonorg estrel, norethynodrel and norethisterone induced ER-beta-activating functio ns in a dose-dependent manner. Luciferase activity dire to estrogen stimula tion served as a positive control. Our results indicate that progestins have different effects on the activiti es of ER-alpha and -beta.