Luteinizing hormone (LH) sets into motion a chain of cellular differentiation events that lead to ovulation. It induces both oocyte maturation and the differentiation of granulosa cells (GCs, somatic cells that surround the oocyte) into luteal cells. GCs are critical for oocyte maturation and, hence, ovulation. One of the effects of LH on GCs is to induce signaling through extracellular signal–regulated kinases (ERKs) 1 and 2 (also known as MAPKs 3 and 1). Fan et al. explored the effect of mutations in Erk1 and Erk2 on granulosa cell development and oocyte maturation in mice. GC-specific knockout of both Erk1 and Erk2 resulted in infertility due to failure of oocyte maturation, although oocytes isolated from mutants underwent meiotic maturation when stimulated in vitro. In contrast to its effects in wild-type mice, LH treatment failed to halt GC proliferation [induced by follicle-stimulating hormone (FSH), upstream in the follicle maturation pathway that leads to ovulation] or induce LH-responsive gene expression in these mutants, and mutant granulosa cells failed to differentiate. These phenotypes are similar to those observed in mutants that lack the transcription factor CCAAT/enhancer-binding protein–β (C/EBPβ), and subsequent genetics experiments suggested that C/EBPβ is activated by ERK-mediated phosphorylation. Thus, signaling through ERKs 1 and 2 induced by LH is required for the GCs to support and promote oocyte maturation. A Perspective by Duggavathi and Murphy discusses these results in the broad context of ovulation.
H.-Y. Fan, Z. Liu, M. Shimada, E. Sterneck, P. F. Johnson, S. M. Hedrick, J. S. Richards, MAPK3/1 (ERK1/2) in ovarian granulosa cells are essential for female fertility. Science 324, 938–941 (2009). [Abstract] [Full Text]