Figure 20.Signaling pathways and mediators of ovulation. Ovulatory surges of FSH and LH stimulate cells from multiple follicle compartments to transduce signals that collectively lead to ovulation. LH signaling is transduced by thecal and mural granulosa cells, whereas FSH signaling is transduced by mural granulosa and cumulus cells. Thecal cells (or leukocytes within the theca layer) secrete IL-1, a cytokine that stimulates cumulus cell expansion, and InsL3, a peptide that may trigger a reduction in oocyte cAMP levels. Mural granulosa cells secrete EGF-like ligands, growth factors that transduce the ovulatory response to the cumulus cells. In addition, they secrete versican and AdamTS-1, both of which become components of the cumulus cell matrix. Inter--trypsin inhibitor from the bloodstream similarly relocates to form part of the cumulus cell matrix. PGE2 generated by cumulus cells acts in an autocrine fashion to promote cAMP production that enhances ovulatory signaling cascades. Oocyte morphogens including GDF-9, BMP-15, and BMP-6, along with multiple other signaling molecules generated both within and outside the follicle, modulate cumulus cell, mural granulosa cell, and theca cell responses to ovulatory signals. IL-1, interleukin-1; InsL3, insulin-like peptide 3; Egf-L, EGF-like ligands; II, inter--trypsin inhibitor; PGE2, prostaglandin E2.