Northwest Nazarene University, 623 S. University Blvd, Nampa, ID 83686, U.S.A.
Departamento de Bioquímica, Instituto Nacional de Cardiología, Mexico City 14080, México.
Biosci Rep. 2020 Apr 30;40(4). doi: 10.1042/BSR20193512.
Cells lining the uterus are responsible for storage and secretion of carbohydrates to support early embryonic development. Histotrophic secretions contain glycogen and glycolytic products such as lactate and pyruvate. Insufficient carbohydrate storage as glycogen has been correlated with infertility in women. While it is clear that changes in estrogen (17-β-estradiol (E2)) and progesterone (P4) in vivo affect the distribution of glucose in the uterine cells and secretions, the biochemical mechanism(s) by which they affect this crucial allocation is not well understood. Furthermore, in cultured uterine cells, neither E2 nor P4 affect glycogen storage without insulin present. We hypothesized that P4 and E2 alone affect the activity of glycolytic enzymes, glucose and glycolytic flux to increase glycogen storage (E2) and catabolism (P4) and increase pyruvate and lactate levels in culture. We measured the rate of glucose uptake and glycolysis in a mink immortalized epithelial cell line (GMMe) after 24-h exposure to 10 μM P4 and 10 nM E2 (pharmacologic levels) at 5 mM glucose and determined the kinetic parameters (Vmax, Km) of all enzymes. While the activities of many glycolytic enzymes in GMMe cells were shown to be decreased by E2 treatment, in contrast, glucose uptake, glycolytic flux and metabolites levels were not affected by the treatments. The cellular rationale for P4- and E2-induced decreases in the activity of enzymes may be to prime the system for other regulators such as insulin. In vivo, E2 and P4 may be necessary but not sufficient signals for uterine cycle carbohydrate allocation.
子宫壁细胞负责储存和分泌碳水化合物,以支持早期胚胎发育。组织滋养分泌物含有糖原和糖酵解产物,如乳酸盐和丙酮酸。糖原储存不足与女性不孕有关。虽然很明显,体内雌激素(17-β-雌二醇(E2))和孕激素(P4)的变化会影响葡萄糖在子宫细胞和分泌物中的分布,但它们影响这种关键分配的生化机制尚不清楚。此外,在培养的子宫细胞中,即使存在胰岛素,E2 或 P4 也不会影响糖原的储存。我们假设 P4 和 E2 单独影响糖酵解酶的活性,从而增加糖原的储存(E2)和分解代谢(P4),以及增加丙酮酸和乳酸盐水平在培养物中。我们测量了在 5mM 葡萄糖下,GMMe(一种貂上皮永生化细胞系)在 24 小时暴露于 10μM P4 和 10nM E2(药理水平)后的葡萄糖摄取和糖酵解速率,并确定了所有酶的动力学参数(Vmax、Km)。虽然 GMMe 细胞中许多糖酵解酶的活性被 E2 处理降低,但相反,葡萄糖摄取、糖酵解通量和代谢物水平不受处理的影响。P4 和 E2 诱导的酶活性降低的细胞机制可能是为胰岛素等其他调节剂做好准备。在体内,E2 和 P4 可能是必需的,但不是子宫周期碳水化合物分配的充分信号。