HORMONALLY REGULATED EXPRESSION AND ALTERNATIVE SPLICING OF KIT-LIGAND MAY REGULATE KIT-INDUCED INHIBITION OF MEIOSIS IN RAT OOCYTES

Mutations in the genes encoding the Kit tyrosine kinase receptor or ki t ligand (KL) cause numerous phenotypic defects, including sterility. In the postnatal ovary, Kit is expressed on the oocyte surface and KL is produced by the surrounding granulosa cells, but its function in th ese cells is still unknown. The purpose of this study was to determine the role KL/Kit interactions play in the regulation of oocyte meiosis . Here, we demonstrate that meiotically arrested rat oocytes that are microinjected With Kit antisense oligonucleotides have decreased Kit e xpression. This decreased expression is associated with an increased a bility of these oocytes to resume meiosis compared with those microinj ected with missense oligonucleotides or buffer alone. In addition, ooc ytes cultured in the presence of KL were delayed in their resumption o f meiosis, but KL could not enhance the meiosis inhibitory effects of dibutyryl cAMP, suggesting that KL operates through a mechanism that i s independent of cAMP. Human chorionic gonadotropin-induced meiotic re sumption in oocytes was accompanied by a shift in follicular granulosa cell KL expression from membrane-bound to soluble forms and a loss of expression of both forms of KL in cumulus cells. Thus, KL-activated K it inhibits meiotic progression, and the in vivo luteinizing hormone-s timulated resumption of meiosis may negate Kit activity by a localized decrease in KL expression and by altering the form of KL produced wit hin the follicle. (C) 1997 Academic Press.