EFFECT OF ALKALOIDS IN CIGARETTE-SMOKE ON HUMAN GRANULOSA-CELL PROGESTERONE SYNTHESIS AND CELL VIABILITY

Inhibition of corpus lutea progesterone synthesis by alkaloids in ciga rette smoke might, in part, explain the generally poorer outcome of pr egnancy in women who smoke. The present experiments evaluated the effe cts of alkaloids in cigarette smoke on progesterone biosynthesis and c ell viability. Studies were initiated using primary cultures of human granulosa cells. Incubation of the granulosa cells with nicotine, coti nine, anabasine, the combination of nicotine, cotinine and anabasine, or an aqueous extract of cigarette smoke resulted in inhibition of pro gesterone synthesis. The alkaloids and smoke extract decreased the DNA content of the culture dish. These findings suggested a cytotoxic eff ect of the alkaloids. Growth curves conducted using the gonadotropin-r esponsive, progesterone-synthesizing MA-10 cell line confirmed growth inhibition by the alkaloids and smoke extract. Together, these data su ggest that cigarette alkaloids inhibit cellular progesterone synthesis both by inhibiting progesterone synthesis and by causing less-specifi c toxic effects to the cell.