127. Platelet derived growth factors and receptors contribute toward development of the corpus luteum

Abstract

In this study the expression of the family of platelet derived growth factors (PDGF) and receptors in the ovarian corpus luteum was identified and characterized, and an effect of their activity on development of the corpus luteum revealed. Gonadotropin-stimulated immature rats were utilized as a model of induced ovulation, luteogenesis and pseudopregnancy, and levels of mRNA for platelet derived growth factors (PDGF-A, PDGF-B, PDGF-C and PDGF-D) and receptors (PDGF-Rα and PDGF-Rβ) in response to gonadotropins were investigated. Intraperitoneal injection of immature rats with pregnant mare’s serum gonadotropin (PMSG) followed 54 h later with human chorionic gonadotropin (hCG) resulted in a significant increase in ovarian mRNA levels for PDGF-Rβ and its ligands, PDGF-B and PDGF-D, as early as 4 h after hCG injection. Gonadotropin regulation of PDGF-B was confirmed by in vitro promoter–reporter assays, which showed a 2–3-fold increase in PDGF-B promoter activity in response to luteinising hormone (LH), and inhibition studies implicated protein kinase A, phosphatidylinositol 3-kinase and mitogen activated protein kinase signaling pathways in the LH-induced upregulation. In the corpus luteum, PDGF-Rα was localized to a subset of luteal steroidogenic cells, and PDGF-Rβ to cells of the luteal microvasculature. PDGF-A, PDGF-B and PDGF-C were also identified in a population of luteal steroidogenic cells. Intraovarian injection of an inhibitor of PDGF receptor activity, the tyrphostin AG1295, prior to injection of hCG in PMSG-primed immature rats resulted in a significant 22.85 ± 10.7% decrease in corpora lutea per treated ovary in comparison to the contralateral vehicle-injected control ovary. In addition, the treated ovary of 3 of 12 rats showed widespread hemorrhage throughout the entire ovary, indicating a possible role for PDGF receptor activity in maintenance of the ovarian vasculature. In summary, these data identify expression of members of the family of platelet derived growth factors and receptors in cells within the corpus luteum and reveal a role during development of the corpus luteum.