Potential endocrine function of the glycolytic enzyme glucose-6-phosphate isomerase during implantation

Glucose-6-phosphate isomerase (GPI) is a glycolytic enzyme that also acts as autocrine motility factor, a secreted protein that stimulates tumor cell motility. We have shown that GPI is required for embryo implantation in the domestic ferret. Here, we tested the hypothesis that GPI is produced and secreted into the bloodstream by ferret luteal cells. Plasma GPI activity increased significantly during the pre-implantation period in both pregnant and pseudopregnant ferrets. Explants from Corpus luteum (CL) and follicles of the pre-implantation period were cultured to ascertain their ability to secrete GPI. The medium of cultured luteal extracts contained significantly more GPI activity than the medium of cultured follicles, a control tissue. GPI activity in the medium increased significantly with increasing pregnancy stage, from pregnancy days 3 to 12. However, GPI activity within explant homogenates was the same in CL and follicles and at all days of pregnancy. Thus, CL but not follicles, secrete GPI during the pre-implantation period. Our findings suggest that GPI may be acting in an endocrine manner, being secreted from the CL into the blood, and acting to promote implantation, which occurs at a distant site, the uterus.