Human granulosa cell tumor: stimulation of steroidogenesis by gonadotropins in vitro

A 59-year-old previously oophorectomized woman underwent surgery for a recurrent malignant granulosa cell tumor. Specimens and dispersed cells from the tumor tissue were incubated for 2 hr and cultured for 48 hr, respectively, with and without gonadotropins. Steroids and cyclic AMP (cAMP) concentrations were measured in the incubation and culture media. Incubated specimens from the tumor tissue released measurable amounts of cAMP, progesterone, and estradiol into the medium. Human follicle-stimulating hormone (FSH) 1 microgram/ml significantly stimulated the formation of cAMP and both steroids. Human luteinizing hormone (LH) 1 microgram/ml stimulated cAMP and progesterone but not estradiol release. Human chorionic gonadotropin (hCG) 10 micrograms/ml stimulated cAMP and progesterone formation in tumor tissue but was totally devoid of effect on estradiol release. In the tissue culture experiments progesterone and estradiol were formed in considerable amounts, with a higher capacity for progesterone than for estradiol. Progesterone formation was stimulated by FSH and hCG, while estradiol release was stimulated only by hCG. The addition of testosterone significantly enhanced estradiol formation in both incubation and culture experiments. It is concluded that the steroidogenesis of this granulosa cell tumor is sensitive to gonadotropins.