Human ovarian surface epithelial (OSE) cells express LH/hCG receptors, and hCG inhibits apoptosis of OSE cells via up-regulation of insulin-like growth factor-1.
Gonadotropins including luteinizing hormone (LH) or human chorionic gonadotropin (hCG) have been implicated as playing an important role in the development of epithelial ovarian carcinomas, most of which are believed to originate from the ovarian surface epithelium (OSE). To address this issue, we examined the expression of LH/hCG receptors and the influence of hCG on cell proliferation and on the apoptosis of cultured human OSE cells. RT-PCR and binding assay revealed that OSE cells express the LH/hCG receptor mRNA and have specific binding activity for hCG. Treatment with hCG stimulated the proliferation of OSE cells in a dose-dependent manner. In addition, hCG treatment inhibited the apoptosis of OSE cells induced by serum deprivation. Among the apoptosis-related genes, hCG treatment did not change the mRNA levels of bcl-2, bax and IGF-1 receptor but significantly increased that of IGF-1. Treatment with IGF-1 alone also suppressed the apoptosis of OSE cells, and treatment by hCG along with neutralization antibody against IGF-1 receptor reversed the anti-apoptotic effect of hCG. Accordingly, LH/hCG signaling followed by up-regulation of IGF-1 is involved in the inhibition of apoptosis of OSE cells, the possible histogenetic origin of epithelial ovarian carcinomas.
Kuroda
H
H
Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Kyoto, Japan.
Mandai
M
M
Konishi
I
I
Tsuruta
Y
Y
Kusakari
T
T
Kariya
M
M
Fujii
S
S
D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D053938:DNA Fragmentation; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D007457:Iodine Radioisotopes / Q000378:metabolism; D010053:Ovary / Q000187:drug effects / Q000378:metabolism*; D011974:Receptors, LH / Q000235:genetics / Q000378:metabolism*
D006063:Chorionic Gonadotropin; D007457:Iodine Radioisotopes; D011974:Receptors, LH; D007334:Insulin-Like Growth Factor I