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The Production of Progesterone, Androgens, and Estrogens by Granulosa Cells, Thecal Tissue, and Stromal Tissue from Human Ovaries in Vitro ^*

KENNETH P. McNATTY, ANASTASIA MAKRIS, CAMILLO DEGRAZIA, OSATHANONDH RAPIN and KENNETH J. RYAN

Laboratory of Human Reproduction and Reproductive Biology, Harvard Medical School Boston, Massachusetts 02115

Address requests for reprints to: K. P. McNatty, Laboratory of Human Reproduction and Reproductive Biology, 45 Shattuck Street, Boston, Massachusetts 02115.

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 (>8 mm diameter) or small (<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 (₄), testosterone, dihydrotestosterone, es-trone, 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, ₄ (,)tes -tosterone, dihydrotestosterone, estrone, and (E₂No 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 )_4. During the preovulatory) phase, cells from large follicles (>8 mm diameter) differentiate from an estrogen-secreting state into a P- and, to a lesser extent,(an)₄(-secreting one. By contrast, during follicular atresia, gran-ulosa cells continue to synthesize )₄bu t their capacity to syn-thesize 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 >., than (E)₂By contrast, during follicular atresia, (thecal tissue retains its capacity to synthesize >)₄ but loses much of its capacity to synthesize E_2. 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.

Itis 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. That is, the granulosa cell secretions may accumulate within the intrafollicular spaces, whereas much of the thecal secretions may enter the blood stream, so that the different steroid-producing tissues of the follicle may exert their primary effects at different sites.

^* This work was supported by USPHS Grant HD-07923.

Recipient of a Harkness Fellowship from the Commonwealth Fund of New York.

Received October 19, 1978.

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