STEROID-LEVELS IN OVARIAN FOLLICULAR-FLUID RELATED TO FOLLICLE SIZE AND HEALTH-STATUS DURING THE NORMAL MENSTRUAL-CYCLE IN WOMEN

Steroid levels in 308 follicular fluid (FF) aspirates obtained during laparotomy from 116 women with normal ovarian function were related to the size (> 1 mm diameter) and health of the aspirated follicles and the phase of the menstrual cycle in which the FF sampling was done. The percentage of granulosa cells (g.c.) in the DNA S phase (S fraction) in each FF aspirate was determined by flow cytometry and used to classify non-pre-ovulatory follicles as healthy or atretic. A significant correlation between g.c. DNA S fraction and concentration of oestradiol (E2) in FF (FF-E2) was found, restricted to non-pre-ovulatory follicles with diameter > 6 mm. This evidence supports the notion that E2 acts as a local g.c. mitogen in these follicles, but also indicates that other factors may be required to stimulate g.c. proliferation in the smaller antral follicles (.ltoreq. 6 mm diameter). The pattern of steroids in FF of healthy follicles was related to the stage of follicular development, being predominantly ''androgenic'' in small follicles (.ltoreq. 6 mm diameter), ''oestrogenic'' in larger non-pre-ovulatory follicles (> 6 mm diameter) and ''progestagenic'' in pre-ovulatory follicles. In contrast, atretic follicles of all sizes (2-13 mm diameter) exhibited an ''androgenic'' pattern of steroids in FF. The intrafollicular hormonal milieu in the larger healthy non-pre-ovulatory and in preovulatory follicles varied as a function of menstrual cycle phase, whereas that in small follicles (healthy as well as atretic) and in larger atretic follicles remained ''androgenic'' through all the phases of the cycle. We conclude that small human ovarian follicles (.ltoreq. 6 mm diameter) may develop and function independently of cyclic gonadotrophin secretion during the menstrual cycle, whereas development beyond 6 mm diameter requires cyclic pituitary function.