Molecular action of norgestimate: new developments.

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Paris F, Balaguer P, Rimbault F, Gaspari L, Sultan C

Molecular action of norgestimate: new developments.

Gynecol Endocrinol. 2015 Jun;31(6):487-90. doi: 10.3109/09513590.2015.1016904. Epub 2015 May 13.

PubMed ID

25970022 [ View in PubMed

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Abstract

BACKGROUND: Acne occurs because the sebaceous glands are overstimulated by high levels of androgens or are hypersensitive to normal levels of testosterone. In women with mild or moderate acne, the association of norgestimate (NG), and ethinyl estradiol (EE) is an effective treatment. This is related to the effect of oral contraceptives on androgen production and transport and the antiandrogenic properties of NG itself. DESIGN: The present work was undertaken to find out whether NG and its derivative, 17-deacetylnorgestimate(dNG), present steroid activities other than antiandrogen activities, using human progesterone receptor(PR), estrogen receptor alpha(ERalpha) and beta(ERbeta), glucocorticoid receptor(GR) and mineralocorticoid receptor(MR)-responsive cell lines. RESULTS: We confirmed that NG and its metabolite were progestogen partial agonists (EC50 of 13 and 11.1 nM) and ERalpha selective agonists (EC50 of 30.4 and 43.4 nM), as well as full antagonists of low affinity for GR (IC50 of 325 and 255 nM) and moderate affinity for MR (IC50 of 81.2 and 83.7). CONCLUSION: We demonstrated that NG and dNG have full progestogen and weak estrogenic (through ERalpha) properties, which could explain in part the efficacy of NG in association with EE for the treatment of moderate acne in women. Moreover, their antagonist MR activity might have a favorable impact on cardiovascular risk, atherosclerosis and lipid profiles.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Norgestimate	Estrogen receptor alpha	Protein	Humans	Yes	Agonist	Details