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

Abstract

The present study was undertaken to determine the differences in steroidogenic potential of isolated granulosa cells from normal and polycystic ovaries in vitro. Granulosa cells isolated from human ovarian follicles were cultured in a chemically defined medium containing gonadotropins and/or testosterone for 18 days.The effect of human LH on progesterone (P) production of granulosa cells from normal ovaries in the mid-follicular phase was dose-dependent in the concentration ranging from 1 to 100ng/ml. The cultured granulosa cells from normal ovaries responded significantly to LH (100ng/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 testosterone 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 testosterone (T: 100ng/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 (200ng/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 midfollicular phase. The cultured granulosa cells from polycystic ovaries, and also those from normal follicles under 6mm in diameter in the early and mid-follicular phases of the menstrual cycle, had the capacity to biosynthese E2 in the presence of exogenous T and FSH.These results strongly suggest that an intrinsic defect in the aromatase enzyme system may not exist in patients with polycystic ovaries, and that 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.