Regulation of rat uterine steroid receptors by nomegestrol acetate, a new 19-nor-progesterone derivative.
The regulatory effects of nomegestrol acetate (NOM-Ac: 17 alpha-acetoxy-6 alpha-methyl-19-nor-pregna-4,6-diene-3,20-dione), a new 19-nor-progesterone derivative, active p.o. progestin, were studied on rat uterine estrogen (ER) and progestogen receptor (PgR) levels. The actions of estradiol (E2), progesterone (P) and various progestins were investigated. The effects of E2 were reproduced with 5 micrograms/animal: a 2-fold increase in activated ER level in the nucleus at 30 min, 2-fold stimulation of cytosolic ER replenishment at 48 hr and a 4-fold induction of PgR synthesis at 48 hr. The negative regulatory effects of P were also reproduced at doses ranging from 0.25 to 2 mg/animal: inhibition of basal and E2-stimulated cytosolic ER replenishment and inhibition of E2-induced PgR synthesis. NOM-Ac reproduced these negative regulatory effects. The 50% effective doses in reducing estrogen receptor levels and the corresponding potencies relative to P showed NOM-Ac to be 2.4-fold more active than P and to present, when compared to the other progestins, the highest antiestrogenic capacity. Furthermore, in contrast with norethisterone acetate, a 19-nor-testosterone derivative, it was completely devoid of estrogenic potency.
Botella
J
J
Centre de Recherche, Laboratoires Theramex, Principauté de Monaco.
Duc
I
I
Delansorne
R
R
Paris
J
J
Lahlou
B
B
D000818:Animals; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D008535:Megestrol / Q000031:analogs & derivatives* / Q000494:pharmacology; D045167:Progesterone Congeners / Q000494:pharmacology*; D051381:Rats; D011960:Receptors, Estrogen / Q000032:analysis / Q000187:drug effects*; D011980:Receptors, Progesterone / Q000032:analysis / Q000187:drug effects*; D014599:Uterus / Q000032:analysis / Q000187:drug effects*
D045167:Progesterone Congeners; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C047637:nomegestrol; D004958:Estradiol; D008535:Megestrol