Novel signaling pathways that control ovarian follicular development, ovulation, and luteinization

The interactions of peptide and steroid hormone signaling cascades in the ovary are critical for follicular growth, ovulation, and luteinization. Although the pituitary gonadotropins follicle-stimulating hormone (FSH) and luteinizing hormone (LH) play key regulatory roles, their actions are also dependent on other peptide signaling pathways, including those stimulated by insulin-like growth factor-1 (IGF-1), transforming growth factor-beta (TGF-beta) family members (e.g., inhibin, activin, growth differentiation factor-9, bone morphogenic proteins), fibroblast growth factor, and Wnts (via Frizzled receptors). Each of these factors is expressed and acts in a cell-specific manner at defined stages of follicular growth. IGF-1, estrogen, and FSH comprise one major regulatory system. The Wnt/Frizzled pathways define other aspects relating to ovarian embryogenesis and possibly ovulation and luteinization. Likewise, the steroid receptors as well as orphan nuclear receptors and their ligands impact ovarian cell function. The importance of these multiple signaling cascades has been documented by targeted deletion of specific genes. For example, mice null for the LH-induced genes progesterone receptor (PR) and cyclo-oxygenase-2 (COX-2) fail to ovulate. Whereas PR appears to regulate the induction of novel proteases, COX-2 appears to regulate cumulus expansion. This review summarizes some new aspects of peptide and steroid hormone signaling in the rodent ovary.