The ontogeny of 11 beta-hydroxysteroid dehydrogenase type 2 and mineralocorticoid receptor gene expression reveal intricate control of glucocorticoid action in development.
The ontogeny of 11 beta-hydroxysteroid dehydrogenase type 2 and mineralocorticoid receptor gene expression reveal intricate control of glucocorticoid action in development.
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DOI：
10.1210/en.137.2.794
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发表时间：
1996-02-01
期刊：
影响因子：
4.8
通讯作者：
Seckl, JR
中科院分区：
文献类型：
--
作者：
Brown, RW;Diaz, R;Seckl, JR
糖皮质激素在发育和“胎儿编程”中发挥重要作用。胎儿暴露于过量的糖皮质激素会降低出生体重，并导致后期高血压。为了进一步研究这些过程，我们已经确定了详细的个体发育的11 β-羟类固醇脱氢酶2型（11 β-HSD 2，这有力地灭活糖皮质激素）和盐皮质激素受体（MR）的原位杂交从胚胎第9.5天（E9.5，任期= E19），直到出生后的小鼠。E9.5-E12.5的广泛丰富的11 β-HSD 2 mRNA表达在接近E13时急剧变化为有限的组织特异性模式（肾脏、后肠、睾丸、胆管、肺和少数脑区域（后来在小脑、丘脑、中脑顶部、脑桥和海马下托附近的神经上皮区域中观察到））。胎盘（胎盘带）和胚外膜表达丰富的11 β-HSD 2 mRNA，直到E15.5，但这在E16.5附近停止。目前还不清楚啮齿类动物长期胎盘11 β-HSD活性在多大程度上是由于持续存在的11 β-HSD 2蛋白。从E13.5开始观察到令人信服的MR mRNA表达，包括垂体、心脏、肌肉和脑膜，随后在肠道、肾脏、胸腺、肺的离散区域和几个脑区域（包括海马、中脑和下丘脑）中表达。11 β-HSD 2和MR在肾脏和结肠中清楚地共定位于E18.5附近，并且可能在肺的离散区域（E14-15）和海马下托附近的神经上皮中这样做。可能在其他地方MR是非选择性的，11 β-HSD 2参与保护胎儿组织中的糖皮质激素受体。与以往酶学研究的比较表明，11 β-HSD 2 mRNA的变化模式很可能被转化为酶活性，并在人类发育中有显着的相似之处。
Glucocorticoids play important roles in development and 'fetal programming'. Fetal exposure to excess glucocorticoids reduces birth weight and causes later hypertension. To investigate these processes further we have determined the detailed ontogeny of 11 beta-hydroxysteroid dehydrogenase type2 (11 beta-HSD2, which potently inactivates glucocorticoids) and the mineralocorticoid receptor (MR) by in situ hybridisation from embryonic day 9.5 (E9.5, term = E19) until after birth in the mouse. Widespread abundant 11 beta-HSD2 mRNA expression from E9.5-E12.5 changes dramatically at approximate to E13 to a limited tissue-specific pattern (kidney, hindgut, testis, bile ducts, lung and a few brain regions (later seen in cerebellum, thalamus, roof of midbrain, neuroepithelial regions in pons and near the subicular hippocampus)). Placenta (labyrinthine zone) and extra-embryonic membranes express abundant 11 beta-HSD2 mRNA until E15.5 but this ceases approximate to E16.5. It is unclear to what extent rodent term placental 11 beta-HSD activity is due to persisting 11 beta-HSD2 protein. Convincing MR mRNA expression is seen from E13.5 and includes pituitary, heart, muscle and meninges with expression later in gut, kidney, thymus, discrete areas of lung and several brain regions (including hippocampus, rhinencephalon and hypothalamus). 11 beta-HSD2 and MR clearly co-localise approximate to E18.5 in kidney and colon and might do so in discrete areas of lung (E14-15) and neuroepithelia near the subicular hippocampus. Probably elsewhere MR are non-selective and 11 beta-HSD2 is involved in protecting glucocorticoid receptors in fetal tissues. Comparison with previous enzymology studies suggest the changing pattern of 11 beta-HSD2 mRNA is likely to be translated into enzyme activity and have significant parallels in human development.