Fowden A L, Coulson R L, Silver M
Physiological Laboratory, Cambridge, England.
Endocrinology. 1990 Jun;126(6):2823-30. doi: 10.1210/endo-126-6-2823.
Endocrine regulation of tissue glucose-6-phosphatase activity in utero was examined by measuring enzyme levels in liver and kidneys of fetal sheep during the second half of gestation and after experimental manipulation of fetal plasma cortisol and insulin levels. Tissue glucose-6-phosphatase activities increased toward term in parallel with the rise in fetal plasma cortisol. At birth, the activities were significantly higher than in utero, but significantly less than in adult nonpregnant sheep. Fetal hypophysectomy lowered fetal plasma cortisol and reduced hepatic and renal glucose-6-phosphatase activities compared with those in intact fetuses near term. Conversely, intrafetal cortisol infusion raised fetal plasma cortisol and significantly increased tissue glucose-6-phosphatase activity to values similar to those in older fetuses. When the data from these groups of fetuses and the newborn lambs were combined, there was a significant positive correlation between the plasma cortisol level and the glucose-6-phosphatase activity in both liver and kidney. Fetal hypoinsulinemia was induced by fasting the ewe for 48 h and by fetal pancreatectomy. Fetal hepatic and renal glucose-6-phosphatase activities were higher in fasted than in fed animals, while pancreatectomy had little apparent effect on enzyme activity in either tissue. However, when differences in plasma cortisol were taken into account, hepatic, but not renal, glucose-6-phosphatase activities were higher in both groups of hypoinsulinemic fetuses than would have been observed in normoinsulinemic animals with a similar plasma cortisol level. Partial correlation analysis of the data showed that plasma insulin and cortisol were both significant influences on hepatic glucose-6-phosphatase activity in utero, but plasma cortisol had the more pronounced effect. Cortisol, therefore, appears to be a physiological regulator of tissue glucose-6-phosphatase activity in utero and enhances the glucogenic capacity of the sheep fetus during late gestation.
通过在妊娠后半期以及对胎儿血浆皮质醇和胰岛素水平进行实验性调控后，测量胎羊肝脏和肾脏中的酶水平，研究了子宫内组织葡萄糖-6-磷酸酶活性的内分泌调节。随着胎儿血浆皮质醇水平的升高，组织葡萄糖-6-磷酸酶活性在足月时平行增加。出生时，该活性显著高于子宫内，但显著低于成年未孕绵羊。与足月时的完整胎儿相比，胎儿垂体切除降低了胎儿血浆皮质醇，并降低了肝脏和肾脏中的葡萄糖-6-磷酸酶活性。相反，胎儿体内注入皮质醇提高了胎儿血浆皮质醇，并显著增加了组织葡萄糖-6-磷酸酶活性，使其达到与较大胎儿相似的值。当将这些胎儿组和新生羔羊的数据合并时，血浆皮质醇水平与肝脏和肾脏中的葡萄糖-6-磷酸酶活性之间存在显著的正相关。通过使母羊禁食48小时和进行胎儿胰腺切除术诱导胎儿低胰岛素血症。禁食动物的胎儿肝脏和肾脏中的葡萄糖-6-磷酸酶活性高于喂食动物，而胰腺切除术对两种组织中的酶活性几乎没有明显影响。然而，考虑到血浆皮质醇的差异，两组低胰岛素血症胎儿的肝脏（而非肾脏）葡萄糖-6-磷酸酶活性均高于血浆皮质醇水平相似情况下的正常胰岛素血症动物。对数据进行偏相关分析表明，血浆胰岛素和皮质醇均对子宫内肝脏葡萄糖-6-磷酸酶活性有显著影响，但血浆皮质醇的影响更为显著。因此，皮质醇似乎是子宫内组织葡萄糖-6-磷酸酶活性的生理调节因子，并在妊娠后期增强了绵羊胎儿的糖异生能力。
