Kisliouk, T., Section of Reproduction, Department of Animal Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel
Friedman, A., Section of Immunology, Department of Animal Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel
Klipper, E., Section of Reproduction, Department of Animal Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel
Zhou, Q.-Y., Department of Pharmacology, University of California, Irvine, CA 92697, United States
Schams, D., Institute of Physiology, Technical University of Munich, D-85350 Freising, Germany
Alfaidy, N., INSERM EMI 105, Départment des Sciences du Vivant Sud, Commissariat À l'Energie Atomique de Grenoble, 38000 Grenoble, France
Meidan, R., Section of Reproduction, Department of Animal Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel, Department of Animal Sciences, Faculty of Agricultural, Food and Environmental Quality Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel
Friedman, A., Section of Immunology, Department of Animal Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel
Klipper, E., Section of Reproduction, Department of Animal Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel
Zhou, Q.-Y., Department of Pharmacology, University of California, Irvine, CA 92697, United States
Schams, D., Institute of Physiology, Technical University of Munich, D-85350 Freising, Germany
Alfaidy, N., INSERM EMI 105, Départment des Sciences du Vivant Sud, Commissariat À l'Energie Atomique de Grenoble, 38000 Grenoble, France
Meidan, R., Section of Reproduction, Department of Animal Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel, Department of Animal Sciences, Faculty of Agricultural, Food and Environmental Quality Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel
Prokineticin 1 (PROK1), also termed endocrine gland-derived vascular endothelial growth factor (endocrine gland-derived VEGF), is a newly identified protein assigned with diverse biologic functions. It binds two homologous G protein-coupled receptors, PROKR1 and PROKR2. To better understand the roles of PROK1 and its receptors in ovarian function, their expression was determined in follicles and corpora lutea (CLs) at different developmental stages. PROK1 mRNA levels were low at early luteal stage and midluteal stage, but increased sharply during natural or induced luteolysis. High PROK1 mRNA levels also were found in atretic follicles. This profile of PROK1 expression was opposite to that of the well-established angiogenic factor VEGF. Of the two receptor-type expressions, PROKR1 but not PROKR2 was correlated positively with its ligand. Immunohistochemical staining revealed that PROK1 was located mainly within the muscular layer of arterioles, and during regression it also was localized to macrophages and steroidogenic cells. The expression pattern of ITGB2 mRNA, a leukocyte cell marker, overlapped that of PROK1, thus suggesting that leukocyte infiltration may explain the elevated expression of PROK1 in atretic follicles and regressing CL. Indeed, flow cytometry analyses showed that nearly all beta-2 integrin chain (ITGB2)-positive cells also were stained with anti-PROK1 and that significantly more ITGB2/PROK1 double-stained cells were present in degenerating follicles and CL. Furthermore, when challenged in vitro with PROK1, adherent, mononuclear cell numbers and TNF levels were elevated, indicating that PROK1 triggers monocyte activation. Together, these data suggest that PROK1, acting via PROKR1, may be involved in the recruitment of monocytes to regressing CL and atretic follicles and their consequent activation therein. © 2007 by the Society for the Study of Reproduction, Inc.
