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

Abstract

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.

Expression and functional implications of luteal endothelins in pregnant and non-pregnant dogs

“…Corroborating these results, expression of the vascular endothelial growth factor (VEGF) system also remained unaffected during prepartum luteolysis (Kowalewski 2014). The initially increased vasculogenic and angiogenic activities are evidenced by the expression of members of the VEGF system in steroidogenic and non-steroidogenic cells (Mariani et al 2006, Papa Pde et al 2013.…”

Is the canine corpus luteum an insulin-sensitive tissue?

“…In this study, the authors proposed just a supportive role for GLUT4, in spite of (1) the ~3-fold increase observed in SLC2A4 expression through the CL development, (2) the fact that GLUT4 display the highest capacity of transport glucose (Uldry & Thorens 2004) and (3) the fact that it can be rapidly regulated by insulin (Uldry & Thorens 2004). In CL of dogs, our group has demonstrated a differential expression of glucose transporter 1 (SLC2A1/GLUT1), which accompanied hypoxia during the cycle (Papa et al 2014), pointing out that the CL responds to physiological variations of oxygen tension during dioestrus (Nishimura & Okuda 2015). However, nothing is known about the SLC2A4/GLUT4 expression in CL of dogs.…”

The Dog: Nonconformist, Not Only in Maternal Recognition Signaling

“…The early luteal phase, which follows ovulation, is characterized by strong proliferative and vasculogenic activity driven, at least in part, by hypoxia (Papa et al 2014 ) and associated with increased infi ltration of immune cells (Hoffmann et al 2004a ), cumulatively leading to continuously and rapidly increasing steroidogenic activity. The latter is directly refl ected in elevated expression of steroidogenic acute regulatory (STAR) protein and 3-β-hydroxysteroid-dehydrogenase (3βHSD, HSD3B2) (Kowalewski et al 2006a ;Kowalewski and Hoffmann 2008 ), which is translated into dynamically rising luteal P4 output as discussed above.…”