Biogenesis of estrogens by the human ovary. III. Conversion of cholesterol-4-C14 to estrone.

Although cholesterol has been accepted as a precursor of the neutral steroid hormones, its role in estrogen formation has been subject to much doubt. It was postulated, on the basis of experiments in z&o in the pregnant mare, that cholesterol was not an estrogen precursor (1). The test animal had readily converted radioactive acetate to labeled estrogens, but had failed to convert administered radioactive cholesterol. Furthermore, in the acetate experiment, the serum cholesterol was not significantly labeled. At that time, it was felt that the conversion of neutral steroids to estrogens was not an important pathway, thereby excluding a major precursor role for cholesterol as well (1). A discussion of the validity of these arguments has been published (2). The conversion of neutral steroids to estrogens has now been shown to be, in fact, a quantitatively significant reaction (3, 4), and the conversion in &JO of cholesterol to estrone in a pregnant patient has been demonstrated, although in extremely low yield (5). This is the third of a series of reports on the biogenesis of estrogens by the human ovary (cf. (4, 6)). It had been demonstrated in an earlier study, that acetate-l-Cl4 was converted to cholesterol as well as to estrogens in amounts consistent with a possible precursor role for cholesterol (6), and that progesterone, itself a cholesterol metabolite (7)) could be converted to estrogens in 10% yield (4). In this report, the conversion in vitro of cholesterol-4-Cl4 to estrone by the human ovary is described.