MURINE OOCYTES SUPPRESS EXPRESSION OF LUTEINIZING-HORMONE RECEPTOR MESSENGER-RIBONUCLEIC-ACID BY GRANULOSA-CELLS

This study tested the hypothesis that murine oocytes participate in th e establishment of granulosa cell phenotypic heterogeneity in preovula tory follicles. In these follicles, mural granulosa cells express LH r eceptors (LHR) and LHR mRNA, but expression of these molecules is low or undetectable in cumulus cells. Thus, the expression of LHR mRNA is a marker of the mural granulosa cell phenotype in preovulatory follicl es. Cumulus cells expressed elevated steady-state levels of LHR mRNA w hen oocytes were microsurgically removed from oocyte-cumulus cell comp lexes, and this was prevented by paracrine factor(s) secreted by isola ted oocytes. These factors also suppressed FSH-induced elevation of th e level of LHR mRNA expression by mural granulosa cells isolated from small antral follicles, even when expression was augmented by culturin g granulosa cells on components of basal lamina. Moreover, factor(s) s ecreted by oocytes suppressed the expression of LHR mRNA in mural gran ulosa cells isolated from preovulatory follicles already expressing el evated levels of these transcripts. The ability of oocytes to suppress the LHR mRNA expression by granulosa cells was developmentally regula ted. Oocytes from preantral follicles and mature (metaphase II arreste d) oocytes were less effective in suppressing expression than fully gr own, germinal vesicle (GV)-stage oocytes. Furthermore, two-cell-stage embryos did not suppress LHR mRNA levels. Coculture of isolated oocyte s with granulosa cells affected the synthesis of very few granulosa ce ll proteins detected by fluorography of two-dimensional gels after S-3 5-methionine labeling. Thus, oocyte suppression of FSH-induced LHR mRN A expression is specific in both the suppressing cell type and the eff ects on granulosa cells. It is concluded that the default pathway of g ranulosa cell differentiation produces the mural granulosa cell phenot ype, as represented by the expression of LHR mRNA. This pathway is abr ogated by oocytes. Thus, oocytes play a dominant role in establishing the fundamental heterogeneity of the granulosa cell population of preo vulatory follicles.