Expression, hormonal regulation and function of Kit ligand, the ligand for thec-Kit receptor, in the rat reproductive system.
Creators: name: Ismail, Rubina Siddiqi.
Publisher: name: Université d'Ottawa / University of Ottawa
Year: 1998
Subjects: subject: Biology, Cell.

description: Mice having mutations at the Kit and Mast Cell Growth Factor loci suffer from severe development abnormalities in gametogenesis suggesting that the protein products produced at these loci, Kit receptor and kit ligand (KL), serve an essential role in the reproductive system. The purposes of this study were: (1) to identify the expression Kit and KL in the ovary which is the organ in which gametogenesis occurs in the female animal, (2) to determine the expression of Kit and KL in the female reproductive tract, (3) to determine the influence of hormones and growth factors on the expression of Kit and KL, and (4) to identify the functional significance of KL/Kit interactions in the reproductive system. Kit receptor expression was identified in the oocytes of antral follicles and KL expression was seen in granulosa cells in growing and antral follicles. In antral follicles, KL expression was greatest in cumulus granulosa cells and only those mural granulosa cells closest to the oocyte and antral cavity. Low KL expression was seen in the mural granulosa cells closest to the basement membrane. This pattern of KL expression in antral follicles suggested a role for KL in oocyte function. There was an inhibition of oocyte meiotic maturation when oocytes from antral follicles were cultured in the presence of KL compared to untreated oocytes. Luteinizing hormone (LH) is the key stimulator of oocyte maturation within the follicle. In vivo stimulation with LH resulted in a loss of KL expression in cumulus granulosa cells and a shift in the production of membrane-bound KL to more soluble KL in mural granulosa cells. Thus, LH-stimulated oocyte maturation may be partly mediated by the removal of KL in the cumulus granulosa cells and the production of a potentially less active form of KL by mural granulosa cells. The expression of KL in granulosa cells was upregulated at the transcript level by treatment with FSH, LH, or both in vivo and in vitro, as well as with membrane-permeable analogues of cyclic adenosine monophosphate (cAMP), whereas KL mRNA expression decreased with steroid hormone stimulation. KL but not Kit mRNA expression was seen in the ovarian surface epithelium. KL expression in ovarian surface epithelium derived-cells was influenced by both dibutyryl cAMP and transforming growth factor-$\beta$ stimulation. These studies would indicate that the ovarian surface epithelium is a site of KL production and that this expression can be regulated by ovarian factors. Preimplantation embryos have been previously shown to express Kit receptors. In this study KL expression was demonstrated in oviducts and uteri and gonadotropin-stimulated increases in oviductal KL mRNA expression were seen. Furthermore, preimplantation embryo survival and development were enhanced with KL suggesting that KL has stimulatory effects on the mitotic cell cycle of the embryo. (Abstract shortened by UMI.)