Establishment and characterization of a steroidogenic human granulosa-liketumor cell line, KGN, that expresses functional follicle-stimulating hormone receptor

We established a steroidogenic human ovarian granulosa-like tumor cell line , designated KGN, from a patient with invasive ovarian granulosa cell carci noma. KGN had a relatively long population doubling time of about 46.4 h an d had an abnormal karyotype of 45,XX, 7q-, -22. A steroid analysis of the c ultured medium by RIA performed 5 yr alter the initiation of culture showed that KGN was able to secrete pregnenolone and progesterone, and both drama tically increased after stimulation with (Bu)(2)cAMP. However, little or no secretion of 17 alpha -hydroxylated steroids, dehydroepiandrosterone, andr ostenedione, or estradiol was observed. The aromatase activity of KGN was r elatively high and was further stimulated by (Bu)(2)cAMP or FSH. These find ings showed a pattern similar to that of steroidogenesis in human granulosa cells, thus allowing analysis of naturally occurring steroidogenesis in hu man granulosa cells. Fas-mediated apoptosis of KGN was also observed, which mimicked the physiological regulation of apoptosis in normal human granulo sa cells. Based on these findings, this cell line is considered to be a ver y useful model for understanding the regulation of steroidogenesis, cell gr owth, and apoptosis in human granulosa cells.