Lin DC. et al cloned GPR73 by PCR of a human testis cDNA library. RT-PCR detected expression of GPR73 in brain, spleen, prostate, testis, leukocytes, pancreas, adrenal gland, thyroid, salivary gland, and pituitary. Within the digestive tract, GPR73 was expressed in stomach, throughout the small intestine and colon, and in the rectum.
General function
Receptor
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Cellular localization
Plasma membrane
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Ovarian function
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Kisliouk T et al,2003,the expression of EG-VEGF/PK-1 and its receptors in ovarian steroidogenic cells and EC and compared the regulation of EG-VEGF/PK-1 and VEGF expression in SV40 transformed luteinized human granulosa cell line (SVOG). Normal granulosa or SVOG cells expressed EG-VEGF/PK-1 mRNA. Incubation of SVOG cells with forskolin augmented EG-VEGF/PK-1 expression in a dose-dependent manner. Chemical hypoxia induced by CoCl2 and desferrioxamine mesylate (100 ?M each) markedly reduced EG-VEGF/PK-1. In contrast, hypoxia significantly elevated VEGF mRNA (VEGF165, 189) and protein secretion. Thrombin, like hypoxia, also induced an opposite effect on VEGF and EG-VEGF/PK-1. Whereas EG-VEGF/PK-1 and VEGF were inversely regulated, steroidogenesis and EG-VEGF/PK-1 were positively correlated in SVOG cells. A distinct pattern of ovarian PK receptor (PK-R) expression was observed in which steroidogenic cells predominantly express PK-R1 receptors, whereas corpus luteum-derived EC express high levels of both PK-R1 and PK-R2. Therefore, acting via either PK-R2 or PK-R1, EG-VEGF/PK-1 may have angiogenic as well as nonangiogenic functions in the ovary.
Expression regulated by
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Ovarian localization
Granulosa, Luteal cells
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Expression Pattern of Prokineticin 1 and Its Receptors in Bovine Ovaries During the Estrous Cycle: Involvement in Corpus Luteum Regression and Follicular Atresia. Kisliouk T et al. Prokineticin (PROK) 1, also termed endocrine gland-VEGF, is a newly identified protein assigned with diverse biological 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 (CL) at different developmental stages. PROK1 mRNA levels were low at early and mid luteal stages, but increased sharply during natural or induced luteolysis. High PROK1 mRNA levels were also found in atretic follicles. This profile of PROK1 expression was opposite to that of the well-established angiogenic factor, VEGF. Of the two receptor types expression PROKR1 but not PROKR2, was positively correlated with its ligand. Immunohistochemical staining revealed that PROK1 was mainly located within the muscular layer of arterioles, and during regression it was also 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 ITGB2-positive cells were also 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.
Follicle stages
Corpus luteum
Comment
PROKINETICINS (ENDOCRINE GLAND-VEGF AND BV8) IN THE BOVINE OVARY: EXPRESSION AND ROLE AS MITOGENS AND SURVIVAL FACTORS FOR CORPUS LUTEUM DERIVED- ENDOTHELIAL CELLS Kisliouk T, et al .
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 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 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 [(3)H]-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, TNFalpha 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.