Glycogen synthesis by mink uterine glandular and luminal epithelia (GE and LE) is stimulated by estradiol (E2) during estrus. Subsequently, the glycogen deposits are mobilized to near completion to meet the energy requirements of pre-embryonic development and implantation by as yet undetermined mechanisms. We hypothesized that progesterone (P4) was responsible for catabolism of uterine glycogen reserves as one of its actions to ensure reproductive success. Mink were treated with E2, P4 or vehicle (controls) for three days and uteri collected 24h (E2, P4 and vehicle) and 96h (E2) later. To evaluate E2 priming, mink were treated with E2 for three days, then P4 for an additional three days (E2→P4) and uteri collected 24h later. Percent glycogen content of uterine epithelia was greater at E2+96h (GE=5.71±0.55; LE=11.54±2.32) than E2+24h (GE=3.63±0.71; LE =2.82±1.03), and both were higher than controls (GE=0.27± 0.15; LE=0.54±0.30; P < 0.05). Treatment as E2→P4 reduced glycogen content (GE=0.61±0.16; LE=0.51±0.13), to levels not different from controls, while concomitantly increasing catabolic enzyme (glycogen phosphorylase and glucose 6 phosphatase) gene expression and amount of phosphoglycogen synthase protein (inactive) in uterine homogenates. Interestingly, E2→P4 increased glycogen synthase 1 mRNA and hexokinase mRNA (and protein). Our findings suggest to us that while E2 promotes glycogen accumulation by the mink uterus during estrus and pregnancy it is P4 that induces uterine glycogen catabolism releasing the glucose that is essential to support pre-embryonic survival and implantation.