Steroidogenesis of cultured granulosa cells from normal and polycystic ovaries: Differences in responsiveness to luteinizing hormone and follicle-stimulating hormone.

Abstract
The differences in steroidogenic potential of isolated granulosa cells from normal and polycystic ovaries were determined in vitro. Granulosa cells isolated from human ovarian follicles were cultured in a chemically defined medium containing gonadotropins and/or testosterone [T] for 18 days. The effect of human LH [luteinizing hormone] on progesterone (P) production of granulosa cells from normal ovaries in the mid-follicular phase was dose-dependent in concentrations ranging from 1-100 ng/ml. The cultured granulosa cells from normal ovaries responded significantly to LH (100 ng/ml) by showing an 8- to 20-fold increase in P production, whereas exogenous LH stimulated P production in the cultured granulosa cells from polycystic ovaries to a much lesser extent (2- to 4-fold increase). The accumulation of estradiol (E2)by the cultured granulosa cells, regardless of the follicular size, was very low, if any, in the absence of T and/or FSH. In the absence of FSH, granulosa cells from large follicles in the preovulatory stage were more active (10-fold) in aromatization of exogenous T (100 ng/ml) than those from medium-sized follicles in the mid-follicular phase. The addition of FSH alone failed to stimulate E2 biosynthesis in the absence of T, but exogenous FSH (200 ng/ml) in the presence of T induced a marked increase (10-fold) in aromatase activity of the cultured granulosa cells from medium-sized follicles in the mid-follicular phase. The cultured granulosa cells from polycystic ovaries, and also those from normal follicles under 6 mm in diameter in the early and mid-follicular phases of the menstrual cycle, had the capacity to biosyntheize E2 in the presence of exogenous T and FSH. An intrinsic defect in the aromatase enzyme system may not exist in patients with polycystic ovaries, and the persistent elevation of serum LH may lead to a disturbance of P production in response to exogenous LH in the cultured granulosa cells from polycystic ovaries.

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