title: Molecular action of norgestimate: new developments.
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.
  
  
  METHODS
  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 α(ERα) and β(ERβ), 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 ERα 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).
  
  
  CONCLUSIONS
  We demonstrated that NG and dNG have full progestogen and weak estrogenic (through ERα) 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.
authors.affiliation: INSERM U896, Institut de Recherche en Cancérologie de Montpellier (IRCM) Parc Euromédecine - ICM F-34298 , Montpellier , France .
authors.forename: Françoise
authors.initials: F
authors.lastname: Paris
authors.forename: Patrick
authors.initials: P
authors.lastname: Balaguer
authors.forename: Frédéric
authors.initials: F
authors.lastname: Rimbault
authors.forename: Laura
authors.initials: L
authors.lastname: Gaspari
authors.forename: Charles
authors.initials: C
authors.lastname: Sultan
mesh_terms: D002460:Cell Line; D003280:Contraceptives, Oral, Synthetic / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000819:agonists*; D006801:Humans; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology*; D009644:Norgestrel / Q000031:analogs & derivatives* / Q000494:pharmacology; D011372:Progestins / Q000819:agonists*; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors*
chemical_list: D003280:Contraceptives, Oral, Synthetic; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D000451:Mineralocorticoid Receptor Antagonists; D011372:Progestins; D011965:Receptors, Glucocorticoid; D009644:Norgestrel; C017576:norgestimate
keywords: Androgen receptor; estrogen receptor; hormonal contraception