The production of progesterone, androgens, and estrogens by granulosa cells, thecal tissue, and stromal tissue from human ovaries in vitro.
The concentrations of steroids in antral fluid, the number of granulosa cells, the status of the oocyte, and the diameter of each follicle were determined in human ovaries so that follicles at each stage of the menstrual cycle could be classified as large (greater than or equal to 8 mm diameter) or small (less than 8 mm diameter) and healthy or atretic. The granulosa cells and thecal-enriched tissue from each follicle and the stromal tissue from each ovary were cultured for 6 days in vitro. The amounts of progesterone (P), androstenedione (delta 4), testosterone, dihydrotestosterone, estrone, and estradiol (E2) generated by the different tissues were measured on days 0, 2, 4, and 6 of culture. It was found that granulosa cells, thecal tissue, and stromal tissue all have the biosynthetic capacity to produce P, delta 4, testosterone, dihydrotestosterone, estrone, and E2. No individual steroid-secreting compartment of the ovaries studied, whether part of the follicle or of the stroma, had the exclusive capability of producing any of the above-named steroids at any stage of the menstrual cycle or at any stage of antral follicle growth or atresia. Although the steroids produced by the human follicle appear not to be unique to any one cell type, the patterns of steroidogenesis by the granulosa and thecal compartments differ from one another and from the stroma throughout follicular maturation and atresia. During follicular development, granulosa cells produce large amounts of E2 and small amounts of delta 4. During the preovulatory phase, cells from large follicles (greater than or equal to 8 mm diameter) differentiate from an estrogen-secreting state into a P- and, to a lesser extent, an delta 4-secreting one. By contrast, during follicular atresia, granulosa cells continue to synthesize delta 4, but their capacity to synthesize estrogen is substantially reduced. Furthermore, granulosa cells from atretic follicles are incapable of transforming from an androgen-secreting state into a P-secreting one in tissue culture. During follicular growth, thecal tissue secretes about 2--3 times more delta 4 than E2. By contrast, during follicular atresia, thecal tissue retains its capacity to synthesize delta 4 but loses much of its capacity to synthesize E2. The in vitro capacity of thecal tissue to produce steroids exceeds that of the stroma (on a per weight basis) from 2- to 500-fold. Thecal tissue from healthy but not from atretic follicles is capable of differentiating from an androgen- and estrogen-secreting state to a predominantly P-secreting one in tissue culture. It is postulated that although steroid synthesis may not be rigidly compartmentalized during follicular development, appreciable amounts of the steroids secreted by the granulosa and theca may enter different compartments before leaving the ovary...