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

Abstract

To reveal the well known effect of smoking on the incidence of early abortion, the possible effects of cigarette alkaloids on progesterone and estradiol synthesis were investigated. A suspected cause for early spontaneous abortion is corpus luteum insufficiency. The present experiments evaluate the effects of cigarette smoke alkaloids on progesterone and estradiol biosynthesis. Human granulosa cells were obtained from patients undergoing in vitro fertilization and embryo transfer treatment because of infertility. Incubation of the granulosa cells with cotinine, anabasine, with the combination of nicotine, cotinine and anabasine, or with an aqueous extract of cigarette 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 anabasine 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, these data would suggest that cigarette alkaloids inhibit cellular progesterone synthesis both by inhibiting progesterone synthesis and by causing less specific toxic effects to the cell. In contrast, cigarette smoke alkaloids slightly stimulated or had no effect on estradiol production. These concomitant actions of cigarette alkaloids partly explain the higher incidence of early abortion in pregnant women who smoke.

In vitro assessment of reproductive toxicity of tobacco smoke and its constituents

“…Exposure of cultured human granulosa cells to smoke or nicotine has given mixed results with respect to estradiol synthesis. In some studies (Barbieri et al, 1986b;Vidal et al, 2006), inhibition of estradiol synthesis was reported following treatment with mainstream smoke, environmental tobacco smoke, or nicotine, but similar inhibition was not found by others (Bodis et al, 1997;Gocze et al, 1999;Weiss and Eckert, 1989). In a recent study, human luteinized granulosa cells were exposed to medium conditioned by environmental tobacco smoke and showed a decrease in both estrogen and progesterone production (Vidal et al, 2006).…”

Association of meningioma with reproductive factors

“…30 The hypothesis that smoking may inhibit progesterone synthesis has been evaluated in animal and human cells out- side the brain with inconsistent results. 31,32 However, given these observations, interactive effects could be explored and may explain some of the inconsistencies in human studies. 11,29,[33][34][35][36][37][38][39][40][41] It should be noted that smoking was crudely recorded in this study; data on number of cigarettes smoked, type of cigarette and duration of use was not included on the questionnaire.…”

Neurosteroids in nicotine and morphine dependence

“…Indeed, morphine inhibits the hydroxylation of progesterone in vivo (Rane and Ask 1992) and stimulates the activity of 3α-hydroxysteroid dehydrogenase in the brain in vitro (Jaworska-Feil et al 2000). Moreover, cigarette alkaloids inhibit both progesterone synthesis in cultured human granulosa cells (Gocze et al 1999) and specific P450 enzymes in rat adrenal and testicular cells (Kasson and Hsueh 1985;Barbieri et al 1987). Repetitive exposure to nicotine or morphine induces adaptive changes in the central nervous system that lead to the development of tolerance and physical dependence.…”