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 (P4) and 17ß-oestradiol (E2); 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 1α (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 P4 and E2 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 (0.84gene expression of HIF1A, VEGF and FLT1 as well as in P4 plasma concentrations. FGF2 mRNA correlated with E2 plasma concentrations (r=0.61; P=0.01). 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 P4 production.