Expression and Localization of Secreted Frizzled-related Protein-4 in the Rodent Ovary: Evidence for Selective Up-regulation in Luteinized Granulosa Cells

Secreted frizzled-related protein-4 (sFRP-4) belongs to a family of soluble proteins that have a Frizzled-like cysteine-rich domain and function as modulators of Wnt-Frizzled (Fz) signals. As several Wnts and Fz are expressed at defined stages of follicular development in rodent ovaries, these studies were undertaken to evaluate the hormone-regulated expression and localization of sFRP-4. In the mouse ovary, the expression of sFRP-4 mRNA was up-regulated in granulosa cells of large antral follicles after human chorionic gonadotropin administration and was also elevated in corpora lutea, as determined by RT-PCR and in situ hybridization analyses. In hypophysectomized rat ovaries, sFRP-4 expression was similarly induced by human chorionic gonadotropin and further up-regulated by PRL. PRL also stimulated the secretion of sFRP-4 protein from luteinized rat granulosa cells in culture. Therefore, regulation of sFRP-4 by LH and PRL may be important for modulating Fz-1, which is known to be expressed in periovulatory follicles, and Wnt-4/Fz-4, which are expressed in corpora lutea.