胎盘11β-HSD表达调节与糖皮质激素治疗

Regulation of 11β-hydroxysteroid Dehydrogenase in the Placenta and Association with Glucocorticoid Treatment

糖皮质激素(GC)可对胎儿生长发育产生复杂的效应。胎盘11β-羟基类固醇脱氢酶(11β-HSD)作为糖皮质激素代谢限速酶调节母胎间经胎盘转运糖皮质激素量,其分为11β-HSD1和11β-HSD2两种亚型。11β-HSD在不同物种胎盘之间表达具有种属差异,同一物种的胎盘不同部位表达也不完全一样。胎盘部位11β-HSD表达还随孕龄发生改变。胎盘部位11β-HSD表达调节机制复杂,尚未完全明确。雌激素、孕激素、某些金属离子、缺氧和细胞因子等参与11β-HSD表达调节。产前不同物种给予糖皮质激素后,胎盘11β-HSD表达具有差异,主要表现为灵长类动物胎盘11β-HSD2表达上调,而绵羊等动物11β-HSD2表达下调。胎盘11β-HSD与糖皮质激素的关系研究,将有助于阐明11β-HSD在糖皮质激素治疗中所起的作用以及指导临床用药。

Glucocorticoids （GC） have multiple effects on fetal growth and development. Placental 11β-hydroxysteroid dehydrogenase （11β-HSD） play an important role in regulating glucocorticoid metabolism. There are two subtypes of 11β-HSD： 11β-hydroxysteroid dehydrogenase 1 （11β-HSD1） and 11β-hydroxysteroid dehydrogenase 2 （11β-HSD2）. The mechanism responsible for regulating 11β-HSD expression is complicated and more work is needed to elucidate how these proteins are regulated. However, several factors have been identified that are involved in the regulation of these proteins, including estrogen, progesterone, some metal ions, hypoxia and cytokines.Differential expression of 11β-HSD has been observed not only in the placentas of different species, but also in different regions of the placenta from the same species. Furthermore, expression of placental 11β-HSD changes with the gestational age. Antenatal administration of GC to different species can induce various effects on placental expression of 11β-HSD. For example, 11β-HSD2 expression is up-regulated in primates, but down-regulated in sheep following treatment with GC. The study of the relationship between placental 11β-HSD and the response to GC treatment can help to elucidate the role of 11β-HSD in the GC response, and can help guide the use of GC in the clinic.