STEPWISE REQUIREMENT OF C-KIT TYROSINE KINASE IN MOUSE OVARIAN FOLLICLE DEVELOPMENT

Ovarian follicle development is controlled by the cycling variation of gonadotrophins derived from the central nervous system. Intragonadal signals are also required, especially in the autonomous development of small follicles. Receptor tyrosine kinase c-kit and its ligand SLE (S teel factor) are expressed on the surface of specific populations of f ollicle-forming cells in a contiguous manner and are thought to have i mportant roles in follicular development. We blocked the interaction o f c-kit and its ligand by administering the function-blocking antibody ACK2 to developing mice at various times after birth and monitored ov arian follicle development. A blockade of c-kit function disturbed the onset of primordial follicle development, primary follicle growth, fo llicular fluid formation of preantral follicles, and penultimate-stage ovarian follicle maturation before ovulation. Ovarian follicle growth was dependent on c-kit during the first 5 days after birth when the f unctional FSH receptor is not yet expressed in mouse ovary. In contras t, primordial follicle formation and survival, small preantral or antr al follicle development, ovulation, and luteinization of the ovulated follicle were not affected by this antibody. These findings indicate t he stepwise requirement,of c-kit and its ligand interaction system in the developing ovarian follicle and that c-kit with its ligand support s the autonomous development of ovarian follicle independent of gonado trophins. (C) 1997 Academic Press.