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Endocrinology Vol. 142, No. 1 437-445
Copyright © 2001 by The Endocrine Society

ARTICLES

Establishment and Characterization of a Steroidogenic Human Granulosa-Like Tumor Cell Line, KGN, That Expresses Functional Follicle-Stimulating Hormone Receptor

Yoshihiro Nishi, Toshihiko Yanase, Yi-Ming Mu, Koichi Oba, Isao Ichino, Masayuki Saito, Masatoshi Nomura, Chizu Mukasa, Taijiro Okabe, Kiminobu Goto, Ryoichi Takayanagi, Yoshiko Kashimura, Masafumi Haji and Hajime Nawata

Department of Medicine and Bioregulatory Science (Third Department of Internal Medicine), Graduate School of Medical Sciences, Kyushu University (Y.N., T.Y., Y.-M.M., K.O., I.I., M.S., M.N., C.M., T.O., K.G., R.T., H.N.), 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan; CREST (Core Research for Evolutional Science and Technology) (T.T., K.G., R.T., H.N.) and Division of Internal Medicine, National Kokura Hospital (Y.N.), Harugaoka 10-1, Kokura-Minami-Ku 802-0803, Japan; Division of Internal Medicine, Kyushu-Rosai Hospital (M.H.), Kuzuhara-Takamatsu 1–3-1, Kokura-Minami-Ku 800-0296, Japan; and Division of Gynecology, Kyushu-Rosai Hospital (Y.K.), Kuzuhara-Takamatsu 1-3-1, Kokura-Minami-Ku 800-0296, Japan

Address all correspondence and requests for reprints to: Hajime Nawata, M.D., Ph.D., Department of Medicine and Bioregulatory Science (Third Department of Internal Medicine), Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan. E-mail: nawata{at}mailserver.med.kyushu-u.ac.jp

We established a steroidogenic human ovarian granulosa-like tumor cell line, designated KGN, from a patient with invasive ovarian granulosa cell carcinoma. KGN had a relatively long population doubling time of about 46.4 h and had an abnormal karyotype of 45,XX, 7q-, -22. A steroid analysis of the cultured medium by RIA performed 5 yr after the initiation of culture showed that KGN was able to secrete pregnenolone and progesterone, and both dramatically increased after stimulation with (Bu)2cAMP. However, little or no secretion of 17{alpha}-hydroxylated steroids, dehydroepiandrosterone, androstenedione, or estradiol was observed. The aromatase activity of KGN was relatively high and was further stimulated by (Bu)2cAMP or FSH. These findings showed a pattern similar to that of steroidogenesis in human granulosa cells, thus allowing analysis of naturally occurring steroidogenesis in human granulosa cells. Fas-mediated apoptosis of KGN was also observed, which mimicked the physiological regulation of apoptosis in normal human granulosa cells. Based on these findings, this cell line is considered to be a very useful model for understanding the regulation of steroidogenesis, cell growth, and apoptosis in human granulosa cells.




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