Cigarette smoke-induced cholesterol C-20, 22-desmolase inhibition in pregnancy

In an attempt to demonstrate the physiological importance of cholesterol C-20, 22-desmolase regulation of pregnenolone formation in maternal cigarette smoking during pregnancy, the in vitro effect of cigarette smoke extract on corpus luteal and placental desmolase ability to cleave (26-14C) cholesterol to (14C) isocaproic acid, was studied. Using the reverse-isotope dilution technique, (14C) isocaproic acid was isolated and characterized. With the homogenates of corpora lutea of pregnancy (4 to 9 weeks gestation) the maximal inhibitory effect (98.3%) on desmolase efficiency became evident at equivalent of 4 cigarettes. In response to concentrations of the extract at 1/2, 1, 2 and 4 cigarette equivalents on the preparations of placentae (18 to 20 weeks gestation), a dose-dependent pattern of inhibitory effect was observed (29.1 to greater than 95.1%). These results are consistent with the interpretation that decreased supply of pregnenolone for the biosynthesis of progestational and oestrogenic hormones may be causally related to changes characteristic of cigarette-smoke induced pathologic state. It is suggested that similar studies directed towards alteration in biosynthetic capacity of steroidogenic enzymes may provide the basis for our understanding of molecular events initiated in response to the common insult.