HCG promotes proliferation of uterine leiomyomal cells more strongly than that of myometrial smooth muscle cells in vitro.
Uterine myomas often enlarge rapidly during pregnancy. This rapid increase in size may imply that human chorionic gonadotrophin (HCG) influences cell proliferation in uterine leiomyomata. To assess the direct effect of HCG on normal uterine smooth muscle and uterine leiomyomata, we investigated cell proliferation and the expression of cell cycle-related proteins in these cells. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that HCG/LH receptor was present in both cultured myometrial and leiomyomal cells. Treatment with HCG significantly increased cell proliferation in both myometrial and leiomyomal cells (P < 0.03), especially at an early phase in the 9 day culture. The increase in the viable cell number induced by HCG treatment was significantly greater in leiomyoma cells than in myometrial cells on day 3 in culture (P < 0.03). In leiomyomal cells, the expression of proliferating cell nuclear antigen (PCNA), cyclin E and cdc2 was significantly increased by HCG treatment (P < 0.05) even at the lowest concentration used (3 nmol/l). In myometrial cells, the expression of cyclin E and cdc2 was significantly increased by HCG treatment (P < 0.05) only at the highest concentration used (30 nmol/l). These results suggest that HCG directly promotes the proliferation of myometrial and leiomyomal cells, with the latter showing the greater response of the two.
Horiuchi
A
A
Department of Obstetrics and Gynecology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Japan.
Nikaido
T
T
Yoshizawa
T
T
Itoh
K
K
Kobayashi
Y
Y
Toki
T
T
Konishi
I
I
Fujii
S
S
D000328:Adult; D016203:CDC2 Protein Kinase / Q000378:metabolism; D042846:CDC2-CDC28 Kinases; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000494:pharmacology*; D019927:Cyclin E / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007889:Leiomyoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D009215:Myometrium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011974:Receptors, LH / Q000235:genetics; D012016:Reference Values; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000473:pathology*
D006063:Chorionic Gonadotropin; D019927:Cyclin E; D018809:Proliferating Cell Nuclear Antigen; D011974:Receptors, LH; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases