Co-Authors:
Kisliouk, T., Department of Animal Sciences, Faculty of Agricultural, Food and Environmental Quality Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel
Podlovni, H., Department of Animal Sciences, Faculty of Agricultural, Food and Environmental Quality Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel
Spanel-Borowski, K., Institute of Anatomy, University of Leipzig, Liebigstrasse 13, D-04103, Leipzig, Germany
Ovadia, O., Department of Animal Sciences, Faculty of Agricultural, Food and Environmental Quality Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel
Zhou, Q.-Y., Department of Pharmacology, University of California, Irvine, CA 92697, United States
Meidan, R., Department of Animal Sciences, Faculty of Agricultural, Food and Environmental Quality Sciences, Hebrew University of Jerusalem, Rehovot 76100, Israel
Abstract:
A highly vascular endocrine gland, the corpus luteum (CL) is an excellent model for the study of angiogenic factors. Prokineticins (PK-1 and 2), also termed endocrine-glandderived VEGF and BV8 are newly identified proteins described as selective angiogenic mitogens. We previously identified PK binding sites - two closely homologous G proteincoupled receptors (PK-R1 and PK-R2) in human and bovine ovarian cells, but their function remained unknown. In this study we examined the presence and effects of PKsin CL-derived endothelial and steroidogenic cell types (LEC and LSC, respectively). PK-1 mRNA were identified in CL and follicles by real-time PCR, using primers specific for the bovine PK-1 sequence (retrieved from Bos taurus whole genome shotgun database). PKs were potent angiogenic mitogens for LEC: they enhanced cell proliferation, elevated [3H]-thymidine incorporation, MAPK activation and c-jun/fos mRNA expression. The effects of PK proteins on cell survival were examined by nuclear morphology (DAPI staining), measurement of DNA fragmentation (TUNEL assay) and caspase-3 cleavage. Results obtained by these techniques demonstrated that PKs protected LEC from serum starvation-induced apoptosis. Stress conditions such as serum withdrawal, TNFα and hypoxia markedly increased PK-R2 expression, whereas mRNA levels of PK-R1 remained unchanged. These suggest that the anti-apoptotic effect of PK-1 on LEC may be mediated via PK-R2. PK-1 increased VEGF mRNA expression by LSC implying that it could also indirectly, via VEGF, affect luteal angiogenesis. Together, these findings suggest an important role for PK-1 in luteal function by acting as a mitogen and survival factor in LEC. Copyright © 2005 by The Endocrine Society.