Physiological roles of integrin alpha 6 beta 1 in ovarian functions.

We previously reported that human ovarian cells express integrin beta 1 families. The physiological role(s) of integrins was investigated using in vitro human granulosa cell culture and in vivo mouse ovulation model. In human luteinizing granulosa cell culture obtained from the patients undergoing in vitro fertilization treatment, laminin, which is a ligand for integrin alpha 6 beta 1, suppressed the production of progesterone by granulosa cells. On the other hand, the anti-alpha 6 monoclonal antibody (mAb) GoH3, which partially inhibits the interaction between integrin alpha 6 beta 1 and laminin, enhanced production of progesterone by 2-fold of the control under the culture with laminin, indicating that integrin alpha 6 beta 1 regulates the luteinization of human granulosa cell during the periovulatory phase. In an immature superovulated 13-day-old ICR (CD-1) mice model, intraperitoneal administration of GoH3 induced successful ovulation, whereas no ovulation was observed in the GoH3-nontreated groups, showing that integrin alpha 6 beta 1 is related to gonadotropin-induced follicular growth. These findings suggest that the interaction between integrin alpha 6 beta 1 and laminin plays an important role in the corpus luteum formation and follicular growth.