Molecular Human Reproduction, Vol. 5, No. 7, 607-617,
July 1999
© 1999 European Society of Human Reproduction and Embryology
Human granulosa cells express integrin 
2 and collagen type IV: possible involvement of collagen type IV in granulosa cell luteinization
1 Department of Gynecology and Obstetrics, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, 2 Department of Gynecology and Obstetrics, Kurashiki Central Hospital, Kurashiki, 710-8602, and 3 Institute for Frontier Medical Science, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan
Previously, it has been shown that integrin 
6ß1 expressed on human granulosa cells regulates luteinization in co-operation with its ligand, laminin. In this study, integrin 2 was immunohistochemically demonstrated to be expressed on granulosa and large luteal cells. It was also detected on luteinizing theca interna cells after ovulation. Immunoreactive collagen type IV, which is one of the ligands for integrin 2ß1, was detected around granulosa cells in the pre-ovulatory follicles and its expression was rapidly increased during ovulation. By flow cytometry, collagen type IV was detected on the cell surface of luteinizing granulosa cells isolated from pre-ovulatory follicles, confirming the physiological interaction between granulosa cells and collagen type IV. Collagen type IV in follicular fluid was positively related with progesterone concentration. In 4-day cultures of granulosa cells, collagen type IV in the media was significantly increased by human chorionic gonadotrophin (HCG). The progesterone production was significantly attenuated when granulosa cells were cultured on collagen type IV-coated dishes, suggesting that collagen type IV suppresses granulosa cell luteinization. These findings show that collagen type IV, a ligand for integrin 2ß1, is rapidly produced around luteinizing granulosa cells during ovulation, probably under the control of luteinizing hormone (LH) and suggest that collagen type IV is a new parameter and/or regulator of granulosa cell luteinization in the periovulatory phases.
collagen Type IV/granulosa cells/integrin 
2/luteal cells/luteinization
4 To whom correspondence should be addressed
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