Influence of nicotine, cotinine, anabasine and cigarette smoke extract on human granulosa cell progesterone and estradiol synthesis

To reveal the well known effect of smoking on the incidence of early aborti on, the possible effects of cigarette alkaloids on progesterone and estradi ol synthesis were investigated. A suspected cause for early spontaneous abo rtion is corpus luteum insufficiency. The present experiments evaluate the effects of cigarette smoke alkaloids on progesterone and estradiol biosynth esis. Human granulosa cells were obtained from patients undergoing in vitro fertilization and embryo transfer treatment because of infertility. Incuba tion of the granulosa cells with cotinine, anabasine, with the combination of nicotine, cotinine and anabasine, or with an aqueous extract of cigarett e smoke resulted in inhibition of progesterone synthesis. The alkaloids and smoke extract decreased the DNA content of the culture dish. These latter findings suggested a cytotoxic effect of the alkaloids. Both cotinine and a nabasine slightly stimulated the synthesis of normalized estradiol. However , nicotine, combination of all three alkaloids, and cigarette smoke extract had no significant influence on estradiol production. Taken together, thes e data would suggest that cigarette alkaloids inhibit cellular progesterone synthesis both by inhibiting progesterone synthesis and by causing less sp ecific toxic effects to the cell. In contrast, cigarette smoke alkaloids sl ightly stimulated or had no effect on estradiol production. These concomita nt actions of cigarette alkaloids partly explain the higher incidence of ea rly abortion in pregnant women who smoke.