Androgens and Progestins in the Human Ovarian Follicle: Differences in the Evolution of Preovulatory, Healthy Nonovulatory, and Atretic Follicles*

Abstract

Morphological and histoenzymological criteria allowed classification of large human ovarian follicles into three categories: preovulatory, healthy nonovulatory, and atretic. Follicular fluid steroids were measured in each type of follicle during various phases of the follicular portion of the menstrual cycle. Androstenedione was the principal follicular fluid androgen in all categories. Testosterone and dihydrotestosterone concentrations were, respectively, 7–9÷ and 0.4–0.8÷ that of androstenedione. Androgen concentrations were very low in preovulatory follicles. They showed a further 3-fold decrease between phase I (from the beginning of the estrogen surge to the estrogen peak) and phase III (from the LH surge to ovulation). Atretic follicles had very high concentrations of androgens. Healthy nonovulatory follicles showed intermediate levels which increased progressively during the follicular phase until the onset of atresia. Progesterone and 17-hydroxyprogesterone were present in concentrations of similar magnitude in all follicles except phase III preovulatory, in which progesterone was 4 times more abundant than 17-hydroxyprogesterone. Preovulatory follicles at all phases showed higher progestin concentrations than follicles of other categories. The use of the androstenedione to 17-hydroxyprogesterone and estradiol to androstenedione ratios to tentatively evaluate the efficiency of androgen and estrogen formation allowed further characterization of the three categories. Healthy nonovulatory follicles showed an average efficiency of both reactions, with an increase in the androstenedione to 17-hydroxyprogesterone ratio and a decrease in the estradiol to androstenedione ratio during the periovulatory period. Atretic follicles exhibited a highly efficient transformation of progestin into androgen but a very low aromatization potency. The preovulatory follicle was characterized by a highly efficient aromatization and a very inefficient transformation of progestin into androgen. At phase III, the estradiol to androstenedione ratio was twice that at phase I, whereas the androstenedione to 17-hydroxyprogesterone ratio showed a dramatic 8-fold decrease. These results suggest that the shift of the preovulatory follicle from estrogen to progestin accumulation during phase III is due to a further decrease in the transformation of progestins into androgens and not to a decreased efficiency of aromatization. It must, however, be emphasized that these conclusions were based on determinations of hormone levels in the follicles and not on actual measurements of steroid conversions.