TY - JOUR
T1 - Prokineticins (endocrine gland-VEGF and BV8) in the bovine ovary
T2 - Expression and role as mitogens and survival factors for corpus luteum derived- endothelial cells
AU - Kisliouk, Tatiana
AU - Podlovni, Helena
AU - Spanel-Borowski, Katharina
AU - Ovadia, Oded
AU - Zhou, Qun Yong
AU - Meidan, Rina
PY - 2005/9
Y1 - 2005/9
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Apoptosis
KW - Luteal endothelial cells
KW - Luteal steroidogenic cells
KW - VEGF
UR - http://www.scopus.com/inward/record.url?scp=23844458338&partnerID=8YFLogxK
U2 - 10.1210/en.2005-0297
DO - 10.1210/en.2005-0297
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C2 - 15932929
AN - SCOPUS:23844458338
SN - 0013-7227
VL - 146
SP - 3950
EP - 3958
JO - Endocrinology
JF - Endocrinology
IS - 9
ER -