Kim Sung Tae, Moley Kelle H
Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Biol Reprod. 2009 Jul;81(1):188-98. doi: 10.1095/biolreprod.108.072629. Epub 2009 Feb 4.
Adequate uterine glucose metabolism is an essential part of embryo implantation and the development of an adequate utero-fetal environment. However, expression of facilitative glucose transporters (GLUTs [solute transporter family SLC2A]) and AKT/MAPK/PRKAA (PRKAA) signaling has not been described in the mouse uterine cells, to our knowledge. The objective of this study was to determine the hormonal regulation of SLC2A protein expression and AKT/MAPK/PRKAA signaling in the mouse uterine epithelial cells during estrous cycles and peri-implantation periods. SLC2As 1, 4, 8, and 9B were highly expressed in the luminal and glandular epithelia of estrous stage. In metestrous and diestrous stages, expression of SLC2As 1, 4, 8, and 9B was lower than that in proestrous stage. Levels of activated phospho-AKT (p-AKT), p-MAPK3, and p-MAPK1 also varied during the estrous cycle. Estrogen and progesterone injection in an ovariectomized mouse (delayed implantation model) resulted in a decrease and an increase, respectively, in expression of GLUTs in the luminal epithelial cells of the uterus. The expression of SLC2A1, SLC2A8, SLC2A9B, p-AKT, p-MAPK3/1, and p-PRKAA was increased in the decidual region of the implantation sites and was significantly increased in the uterus of activated implantation. Using an artificial decidualization mouse model, it was also demonstrated that expression of the same GLUTs, p-MAPK3/1, and p-PRKAA was dramatically higher in the decidualized uteri than that in the control uteri. These results suggest that steroid hormones regulate expression of uterine epithelial GLUTs possibly through AKT/MAPK/PRKAA signaling pathways and that glucose utilization may have an important role in decidualization and possibly in the maintenance of pregnancy.
充足的子宫葡萄糖代谢是胚胎着床以及建立适宜的子宫 - 胎儿环境的重要组成部分。然而，据我们所知，在小鼠子宫细胞中尚未对易化性葡萄糖转运蛋白（GLUTs [溶质转运体家族SLC2A]）的表达以及AKT/MAPK/PRKAA（PRKAA）信号传导进行描述。本研究的目的是确定在发情周期和围植入期小鼠子宫上皮细胞中SLC2A蛋白表达和AKT/MAPK/PRKAA信号传导的激素调节。SLC2A1、4、8和9B在发情期的腔上皮和腺上皮中高表达。在动情后期和间情期，SLC2A1、4、8和9B的表达低于发情前期。活化的磷酸化AKT（p - AKT）、p - MAPK3和p - MAPK1的水平在发情周期中也有所变化。在去卵巢小鼠（延迟着床模型）中注射雌激素和孕酮分别导致子宫腔上皮细胞中GLUTs表达的降低和升高。SLC2A1、SLC2A8、SLC2A9B、p - AKT、p - MAPK3/1和p - PRKAA的表达在着床部位的蜕膜区增加，并且在活化着床的子宫中显著增加。使用人工蜕膜化小鼠模型还证明，相同的GLUTs、p - MAPK3/1和p - PRKAA在蜕膜化子宫中的表达明显高于对照子宫。这些结果表明，类固醇激素可能通过AKT/MAPK/PRKAA信号通路调节子宫上皮GLUTs的表达，并且葡萄糖利用可能在蜕膜化以及可能在维持妊娠中起重要作用。
