scholarly journals Localization and Quantification of Cyclic Changes in the Expression of Endocrine Gland Vascular Endothelial Growth Factor in the Human Corpus Luteum

2005 ◽  
Vol 90 (1) ◽  
pp. 427-434 ◽  
Author(s):  
Hamish M. Fraser ◽  
Julie Bell ◽  
Helen Wilson ◽  
Paul D. Taylor ◽  
Kevin Morgan ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Corpus Luteum ◽  
Luteal Phase ◽  
Endocrine Gland ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Prokineticin 2 ◽  
Endothelial Growth Factor ◽  
Human Corpus Luteum

Abstract Angiogenesis is essential for normal growth and function of the corpus luteum. The roles of various angiogenic factors in these events are being elucidated. Endocrine gland vascular endothelial growth factor (EG-VEGF) has recently been described in the human ovary. To define the localization of EG-VEGF mRNA in the corpus luteum and determine changes in its expression, dated human corpora lutea were studied at the early, mid-, and late luteal phases. Quantitative RT-PCR was employed to determine changes in EG-VEGF mRNA and compare expression to its related factor prokineticin-2 and the established angiogenic factor, VEGF. In situ hybridization was used to localize sites of production of EG-VEGF. To investigate whether expression of EG-VEGF was under the influence of LH or progesterone, luteinized granulosa cells were stimulated with human chorionic gonadotropin in the presence or absence of a progesterone synthesis inhibitor. EG-VEGF mRNA increased throughout the luteal phase, whereas there was no change in VEGF mRNA. The relative abundance of RNAs based upon PCR signal intensity showed that VEGF and EG-VEGF were highly expressed, whereas expression of prokineticin-2 was low. EG-VEGF mRNA was localized predominantly to granulosa-derived cells of the corpus luteum. Human chorionic gonadotropin stimulated both VEGF and EG-VEGF mRNA in vitro, but the level of expression was not influenced by progesterone. These results establish that in the human corpus luteum EG-VEGF is principally derived from granulosa lutein cells and that its synthesis is highest during the mid- to late luteal phase.

scholarly journals Angiogenesis in the Human Corpus Luteum: Localization and Changes in Angiopoietins, Tie-2, and Vascular Endothelial Growth Factor Messenger Ribonucleic Acid1

2000 ◽  
Vol 85 (11) ◽  
pp. 4302-4309 ◽  
Author(s):  
Christine Wulff ◽  
Helen Wilson ◽  
Pawlina Largue ◽  
W. Colin Duncan ◽  
David G. Armstrong ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Endothelial Cells ◽  
Growth Factor ◽  
Corpus Luteum ◽  
Luteal Phase ◽  
Corpora Lutea ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Messenger Ribonucleic Acid ◽  
Endothelial Growth Factor

In the menstrual cycle, extensive angiogenesis accompanies luteinization. During luteolysis, endothelial cells die, whereas in a conceptual cycle, the corpus luteum (CL) persists, and endothelial cell survival is extended. A main stimulator for angiogenesis is vascular endothelial growth factor (VEGF), while the angiopoietins (Ang-1 and Ang-2) may be important modulators. The aim of this study was to investigate the localization of Ang-1, Ang-2, their common receptor Tie-2, and VEGF messenger ribonucleic acid (mRNA) at the different stages of the functional luteal phase and after rescue by hCG. Ang-1 mRNA was uniformly expressed at a low level throughout the CL. The signal was highest during the early luteal phase. In contrast, Ang-2 mRNA expression was localized strongly to individual granulosa and thecal luteal and endothelial cells. Administration of hCG was associated with an increase in the Ang-2 mRNA area of expression and grain density in individual luteal and endothelial cells. The Tie-2 receptor mRNA was localized in endothelial cells, and the area of expression was highest during the early luteal phase and during luteal rescue. VEGF mRNA was found exclusively in granulosa luteal cells, and the area of expression was highest in corpora lutea during simulated pregnancy. These results begin to characterize the molecular regulation of the divergent processes involved in luteal angiogenesis during luteinization, luteolysis, and rescue in the human and imply that the angiopoietins are involved during the initial angiogenic phase and in luteal rescue.

scholarly journals Vascular endothelial growth factor increases messenger RNAs encoding cyclooxygenase-II and membrane-associated prostaglandin E synthase in rat luteal cells

2004 ◽  
Vol 183 (3) ◽  
pp. 527-533 ◽  
Author(s):  
T Sakurai ◽  
K Tamura ◽  
H Kogo
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Mrna Expression ◽  
Corpus Luteum ◽  
Prostaglandin E ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Luteal Cells ◽  
Endothelial Growth Factor ◽  
Vegf Mrna Expression

Vascular endothelial growth factor (VEGF) is known to be necessary for the vascularization of the developing corpus luteum. Our recent data suggested that cyclooxygenase-II (COX-II) may play a role in the formation of vascular plexuses in developing corpora lutea of the rat. Here we examined the relationship between VEGF and the expression of prostaglandin (PG)- metabolizing enzymes in rat ovarian luteal cells. VEGF treatment caused a dose-dependent increase in the expression of COX-II and membrane-associated PGE synthase (mPGES) mRNA in cultured rat luteal cells. However, pretreatment of the luteal cells with a selective COX-II inhibitor, NS-398, abolished the VEGF-enhanced mPGES mRNA expression. VEGF also increased PGE2 secretion. Conversely, PGE2 dose-dependently stimulated VEGF mRNA expression. Furthermore, VEGF induced VEGF mRNA expression, but this effect was abolished by NS-398 pretreatment. These findings suggest that VEGF enhances PGE2 production by stimulating COX-II and mPGES expression in rat corpus luteum and that the effect of VEGF on luteal cells may be partially mediated by this stimulation of PGE2 production.

scholarly journals Prokineticins (Endocrine Gland-Derived Vascular Endothelial Growth Factor and BV8) in the Bovine Ovary: Expression and Role as Mitogens and Survival Factors for Corpus Luteum-Derived Endothelial Cells

Endocrinology ◽  
2005 ◽  
Vol 146 (9) ◽  
pp. 3950-3958 ◽  
Author(s):  
Tatiana Kisliouk ◽  
Helena Podlovni ◽  
Katharina Spanel-Borowski ◽  
Oded Ovadia ◽  
Qun-Yong Zhou ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Mrna Expression ◽  
Corpus Luteum ◽  
Serum Starvation ◽  
Endocrine Gland ◽  
Mrna Levels ◽  
Vascular Endothelial ◽  
Steroidogenic Cell ◽  
Endothelial Growth Factor

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-gland-derived vascular endothelial growth factor (VEGF) and BV8 are newly identified proteins described as selective angiogenic mitogens. We previously identified PK binding sites, two closely homologous G protein-coupled 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 PK in CL-derived endothelial and steroidogenic cell types (LEC and LSC, respectively). PK-1 mRNA was 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). PK 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 (4′,6-diamidino-2-phenylindole dihydrochloride staining), measurement of DNA fragmentation (terminal dUTP nucleotide end labeling assay), and caspase-3 cleavage. Results obtained by these techniques demonstrated that PK protected LEC from serum starvation-induced apoptosis. Stress conditions such as serum withdrawal, TNF-α, and hypoxia markedly increased PK-R2 expression, whereas mRNA levels of PK-R1 remained unchanged. These suggest that the antiapoptotic 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.

scholarly journals Prokineticin receptors (version 2020.4) in the IUPHAR/BPS Guide to Pharmacology Database

2020 ◽  
Vol 2020 (4) ◽  
Author(s):  
Rebecca Hills ◽  
Adam J. Pawson ◽  
Philippe Rondard ◽  
Oualid Sbai ◽  
Qun-Yong Zhou
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Amino Acid ◽  
Growth Factor ◽  
Endocrine Gland ◽  
Vascular Endothelial ◽  
High Potency ◽  
Prokineticin 2 ◽  
Selective Agonist ◽  
Macrophage Chemotaxis ◽  
Endothelial Growth Factor

Prokineticin receptors, PKR1 and PKR2 (provisional nomenclature as recommended by NC-IUPHAR [23]) respond to the cysteine-rich 81-86 amino-acid peptides prokineticin-1 (also known as endocrine gland-derived vascular endothelial growth factor, mambakine) and prokineticin-2 (protein Bv8 homologue). An orthologue of PROK1 from black mamba (Dendroaspis polylepis) venom, mamba intestinal toxin 1 (MIT1, [65]) is a potent, non-selective agonist at prokineticin receptors [41], while Bv8, an orthologue of PROK2 from amphibians (Bombina sp., [44]), is equipotent at recombinant PKR1 and PKR2 [48], and has high potency in macrophage chemotaxis assays, which are lost in PKR1-null mice.

scholarly journals Prokineticin receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

2019 ◽  
Vol 2019 (4) ◽  
Author(s):  
Rebecca Hills ◽  
Philippe Rondard ◽  
Oualid Sbai ◽  
Qun-Yong Zhou
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Amino Acid ◽  
Growth Factor ◽  
Endocrine Gland ◽  
Vascular Endothelial ◽  
High Potency ◽  
Prokineticin 2 ◽  
Selective Agonist ◽  
Macrophage Chemotaxis ◽  
Endothelial Growth Factor

Prokineticin receptors, PKR1 and PKR2 (provisional nomenclature as recommended by NC-IUPHAR [23]) respond to the cysteine-rich 81-86 amino-acid peptides prokineticin-1 (also known as endocrine gland-derived vascular endothelial growth factor, mambakine) and prokineticin-2 (protein Bv8 homologue). An orthologue of PROK1 from black mamba (Dendroaspis polylepis) venom, mamba intestinal toxin 1 (MIT1, [65]) is a potent, non-selective agonist at prokineticin receptors [41], while Bv8, an orthologue of PROK2 from amphibians (Bombina sp., [44]), is equipotent at recombinant PKR1 and PKR2 [48], and has high potency in macrophage chemotaxis assays, which are lost in PKR1-null mice.

scholarly journals Expression and localization of vascular endothelial growth factor and its receptors in pig corpora lutea during the oestrous cycle

Reproduction ◽  
2003 ◽  
pp. 393-405 ◽  
Author(s):  
U Boonyaprakob ◽  
JE Gadsby ◽  
V Hedgpeth ◽  
P Routh ◽  
GW Almond
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Northern Blot ◽  
Luteal Phase ◽  
Northern Blot Analysis ◽  
Corpora Lutea ◽  
Vegf Receptor ◽  
Vascular Endothelial ◽  
Vegf Mrna ◽  
Endothelial Growth Factor

Expression and localization of mRNAs for vascular endothelial growth factor (VEGF), VEGF receptor 1 (Flt) and VEGF receptor 2 (KDR) (VEGFR-1 and VEGFR-2, respectively) were investigated in pig corpora lutea. Northern blot analysis of total RNA indicated hybridization of pig VEGF, VEGFR-1 and VEGFR-2 cDNA probes to mRNA transcripts of approximately 3.9, 7.0 and 5.0 kb, respectively. The expression of mRNAs for VEGF and its receptors during the luteal phase (days 4, 7, 10, 13 and 15 after the onset of oestrus) were assessed by northern blot analysis, and hybridization signals were normalized to expression of pig 18S rRNA. Relative hybridization signals of expression of VEGF mRNA appeared to be constant; however, expression of VEGFR-1 mRNA was low on day 4, increased on day 7, and was higher on days 10, 13 and 15 (P<0.05, compared with day 4). In contrast, no changes in expression of mRNA for VEGFR-2 were evident on days 4-13, but a decrease was detected (P<0.05) at day 15. In situ hybridization revealed that VEGF mRNA was localized predominantly in large luteal cells, whereas both VEGFR-1 and VEGFR-2 were localized to small cells. These data indicate that the VEGF system may be involved in the regulation of luteal vasculature throughout the lifespan of the corpus luteum. Although the expression of VEGF mRNA was unchanged during the luteal phase, variations in the expression of VEGFR-1 and VEGFR-2 mRNAs indicate that differential regulation of expression of the VEGF receptors may play a role in the control of VEGF-mediated vascular growth at different phases of development and maturation of the pig corpus luteum.

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