Canine prostaglandin F2α receptor (FP) and prostaglandin F2α synthase (PGFS): Molecular cloning and expression in the corpus luteum

Kowalewski, Mariusz P.; Mutembei, Henry; Hoffmann, Bernd

doi:10.1016/j.anireprosci.2007.06.026

Cited by 34 publications

(26 citation statements)

References 32 publications

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“…Recently, the role of prostaglandins in luteal regression in the nonpregnant bitch has been addressed (Hoffmann et al 2004, Kowalewski et al 2006a, 2008a. As hysterectomy does not interfere with normal ovarian function (Hoffmann et al 1992), a role of CL-derived prostaglandin F2a (PGF2a) acting as a luteolytic agent via para-/autocrine mechanisms was postulated, also in analogy to the situation observed in other species, i.e.…”

Section: Introductionmentioning

confidence: 99%

Canine placenta: a source of prepartal prostaglandins during normal and antiprogestin-induced parturition

et al. 2010

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Expression of cyclooxygenase 2 (COX2, now known as PTGS2), prostaglandin E2 synthase (PTGES, PGES), and prostaglandin F2a synthase (PGFS), of the respective receptors PTGFR (FP), PTGER2 (EP2), and PTGER4 (EP4) and of the progesterone receptor (PGR, PR) was assessed by real-time PCR, immunohistochemistry (IHC), or in situ hybridization (ISH) in utero/placental tissue samples collected from three to five bitches on days 8-12 (pre-implantation), 18-25 (post-implantation), and 35-40 (mid-gestation) of pregnancy and during the prepartal luteolysis. Additionally, ten mid-pregnant bitches were treated with the antiprogestin aglepristone (10 mg/kg bw (2!/24 h)); ovariohysterectomy was 24 and 72 h after the second treatment. Plasma progesterone and 15-ketodihydro-PGF2a (PGFM) concentrations were determined by RIA. Expression of the PGR was highest before implantation and primarily located to the endometrium; expression in the placenta was restricted to the decidual cells. PTGS2 was constantly low expressed until mid-gestation; a strong upregulation occurred at prepartal luteolysis concomitant with an increase in PGFM. PGFS was upregulated after implantation and significantly elevated through early and mid-gestation. PTGES showed a gradual increase and a strong prepartal upregulation. PTGFR, PTGER2, and PTGER4 were downregulated after implantation; a gradual upregulation of PTGFR and PTGER2 occurred towards parturition. ISH and IHC co-localized PGFS, PTGFR, PTGES, and PTGS2 in the trophoblast and endometrium. The changes following application of aglepristone were in the same direction as those observed from mid-gestation to prepartal luteolysis. These data suggest that the prepartal increase of PGF2a results from a strong upregulation of PTGS2 in the fetal trophoblast with the withdrawal of progesterone having a signalling function and the decidual cells playing a key role in the underlying cell-to-cell crosstalk.

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Section: Introductionmentioning

confidence: 99%

Canine placenta: a source of prepartal prostaglandins during normal and antiprogestin-induced parturition

et al. 2010

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“…The steep progesterone (P 4 ) decline observed in pregnant animals before parturition suggests different regulatory mechanisms for the prepartal luteolysis, contrasting with mechanisms regulating the slow luteal regression observed in non-pregnant bitches during late dioestrus. The latter appears to be a passive degenerative process in the absence of an active luteolytic agent of uterine and/or luteal origin (Hoffmann et al 2004, Kowalewski et al 2008b. In this way, the lifespan of the canine corpus luteum (CL) in nonpregnant bitches often exceeds that of pregnancy, which is a peculiarity when compared with other domestic animals and primates.…”

Section: Introductionmentioning

confidence: 99%

Prostaglandin E2 functions as a luteotrophic factor in the dog

Kowalewski¹,

Fox²,

Gram³

et al. 2013

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The luteal phase in dogs is governed by many poorly understood regulatory mechanisms. Functioning of the corpus luteum (CL) is unaffected by hysterectomy. Recently, the role of prostaglandins in regulating canine CL function was addressed suggesting a luteotrophic effect of prostaglandin E 2 (PGE 2 ) during the early luteal phase. However, compelling functional evidence was lacking. The potential of PGE 2 to stimulate steroidogenesis was tested in canine primary luteal cells isolated from developing CL of non-pregnant dogs. In addition, the luteal expression of prostaglandin transporter (PGT) and steroidogenic acute regulatory protein (STAR) was demonstrated and characterized in CL from non-pregnant bitches during the course of dioestrus as well as from pregnant animals during the preimplantation, post-implantation and mid-gestation periods of pregnancy and during luteolysis; the luteal expression of PGE 2 receptors (EP2 and EP4) has been investigated at the protein level throughout pregnancy. Our findings show that PGE 2 is an activator of STAR expression in canine luteal cells from early luteal phase, significantly up-regulating STAR promoter activity and protein expression resulting in increased steroidogenesis. The 3bHSD (HSD3B2) and P450scc (CYP11A1) expression remained unaffected by PGE 2 treatment. The expression of PGT was confirmed in CL during both pregnancy and dioestrus and generally localized to the luteal cells. After initial up-regulation during the earlier stages of the CL phase, its expression declined towards the luteal regression. Together with the demonstration of EP2 and EP4 throughout pregnancy, and the decline in EP2 at prepartum, our findings further support our hypothesis that intra-luteal PGE 2 may play an important role in regulating progesterone secretion in the canine CL.

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“…During this time, the CL undergoes morpho-endocrinological changes in response to gonadotrophic stimuli and local regulatory factors (Hoffmann et al 2004, Kowalewski et al 2008a, 2009, Papa & Hoffmann 2011. Morphological changes following ovulation until late in dioestrus (Sonnack 2009) as well as changes in steroid hormone, prostaglandin and cytokine levels have been described to act as local regulatory factors (Engel et al 2005, Kowalewski et al 2008a, 2008b, Papa & Hoffmann 2011. The lifespan of the CL depends on energetic supply (Downing et al 1995), which may be regulated by steroid hormones (Frolova et al 2009): in endometrial cells, progesterone (P 4 ) directly regulates the expression of glucose transporter type 1 (SLC2A1 gene/GLUT1 protein) through its receptor , activating the signalling pathway Akt/PKA/ PRKAA and increasing the expression and translocation of GLUT1 , the most ubiquitously distributed facilitative glucose transporter responsible for taking up glucose at basal conditions (Palfreyman et al 1992).…”

Section: Introductionmentioning

confidence: 99%

Glucose transporter 1 expression accompanies hypoxia sensing in the cyclic canine corpus luteum

et al. 2014

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The canine corpus luteum (CL) functions as a source of progesterone (P 4 ) and 17b-oestradiol (E 2 ); however, the transport of energy substrates to maintain its high hormonal output has not yet been characterised. This study involved the localisation and temporal distribution of the facilitative glucose transporter 1 and the quantification of the corresponding protein (GLUT1) and gene (SLC2A1) expression. Some GLUT1/SLC2A1 regulatory proteins, such as hypoxia-inducible factor 1a (HIF1A) and fibroblast growth factor 2 (FGF2); mRNAs, such as HIF1A, FGF2 and vascular endothelial growth factor A (VEGFA); and VEGFA receptors 1 and 2 (FLT1 and KDR) were also analysed from days 10 to 70 after ovulation. Additionally, plasma P 4 and E 2 levels were assessed via chemiluminescence. Moreover, the canine KDR sequence has been cloned, thereby enabling subsequent semi-quantitative PCR analysis. Our results demonstrate time-dependent variations in the expression profile of SLC2A1 during dioestrus, which were accompanied by highly correlated changes (0.84!r!0.98; P!0.03) in the gene expression of HIF1A, VEGF and FLT1 as well as in P 4 plasma concentrations. FGF2 mRNA correlated with E 2 plasma concentrations (rZ0.61; PZ0.01). Our data reveal that the glucose transporter is regulated throughout the CL lifespan and suggest that CL depends on the sensing of hypoxia and the status of luteal vascularisation. Moreover, time-dependent expression of GLUT1/SLC2A1 may lie underneath increased metabolic and energetic requirements for sustaining P 4 production.

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Canine prostaglandin F2α receptor (FP) and prostaglandin F2α synthase (PGFS): Molecular cloning and expression in the corpus luteum

Cited by 34 publications

References 32 publications

Canine placenta: a source of prepartal prostaglandins during normal and antiprogestin-induced parturition

Canine placenta: a source of prepartal prostaglandins during normal and antiprogestin-induced parturition

Prostaglandin E2 functions as a luteotrophic factor in the dog

Glucose transporter 1 expression accompanies hypoxia sensing in the cyclic canine corpus luteum

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