title: Effects of nicotine on human luteal cells in vitro: a possible role on reproductive outcome for smoking women.
abstract: We investigated the effect of nicotine and its methylated metabolite, N-methyl-nicotine (M-nicotine), on human luteal cells by measuring release of progesterone and prostaglandins (PGs) from cultured cells and by testing gene expression of vascular endothelial growth factor (VEGF), an angiogenic factor strictly involved in luteal pathophysiology. Primary cultures of human luteal cells were treated for 24 h with nicotine and M-nicotine (from 10(-6) to 10(-11) M) either alone or combined with hCG (25 ng/ml); progesterone and PGs were assayed in the culture medium. In another group of experiments, luteal cells were treated for 24 h with nicotine and M-nicotine (10(-7) M) to perform reverse transcriptase-polymerase chain reaction on VEGF mRNA. Nicotine and M-nicotine negatively affected basal luteal steroidogenesis at all tested concentrations, but neither was able to affect hCG-induced progesterone release. Both substances were able to significantly increase PGF2alpha release from luteal cells, with a dose-related efficacy for M-nicotine. On the contrary, PGE2 release was significantly inhibited by both nicotine and its metabolite. Finally, nicotine was able to increase VEGF mRNA expression significantly, whereas M-nicotine was not. In conclusion, nicotine and M-nicotine can induce a sort of luteal insufficiency by inhibiting progesterone release, probably through modulation of the PG system.
authors.affiliation: Cattedra Di Fisiopatologia Della Riproduzione Umana, Università Cattolica Del Sacro Cuore, 00168 Roma, Italy.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Miceli
authors.forename: Francesca
authors.initials: F
authors.lastname: Minici
authors.forename: Anna
authors.initials: A
authors.lastname: Tropea
authors.forename: Stefania
authors.initials: S
authors.lastname: Catino
authors.forename: Mariateresa
authors.initials: M
authors.lastname: Orlando
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Lamanna
authors.forename: Francesca
authors.initials: F
authors.lastname: Sagnella
authors.forename: Federica
authors.initials: F
authors.lastname: Tiberi
authors.forename: Adriano
authors.initials: A
authors.lastname: Bompiani
authors.forename: Salvatore
authors.initials: S
authors.lastname: Mancuso
authors.forename: Antonio
authors.initials: A
authors.lastname: Lanzone
authors.forename: Rosanna
authors.initials: R
authors.lastname: Apa
mesh_terms: D000328:Adult; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008184:Luteal Cells / Q000187:drug effects* / Q000378:metabolism; D009538:Nicotine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D018722:Nicotinic Agonists / Q000633:toxicity*; D011374:Progesterone / Q000378:metabolism*; D011453:Prostaglandins / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012098:Reproduction / Q000187:drug effects; D012907:Smoking / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: C503244:N-methyl-nicotine; D018722:Nicotinic Agonists; D011453:Prostaglandins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D011374:Progesterone; D009538:Nicotine