The human fetal adrenal produces cortisol but no detectable aldosterone throughout the second trimester.
The human fetal adrenal produces cortisol but no detectable aldosterone throughout the second trimester.
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DOI：
10.1186/s12916-018-1009-7
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发表时间：
2018-02-12
期刊：
影响因子：
9.3
通讯作者：
Fowler PA
中科院分区：
文献类型：
--
作者：
Johnston ZC;Bellingham M;Filis P;Soffientini U;Hough D;Bhattacharya S;Simard M;Hammond GL;King P;O'Shaughnessy PJ;Fowler PA
人胎儿肾上腺高度活跃，与胎盘一起调节胎儿体内循环的孕酮、雌激素和皮质类固醇。出生时，肾上腺通过分泌醛固酮对新生儿盐潴留至关重要，同时需要足够的糖皮质激素来预防肾上腺功能不全。本研究的目的是进行第一次全面分析肾上腺类固醇水平和类固醇生成酶的表达在正常中期妊娠人类胎儿。这是一项对阿伯丁大学和格拉斯哥大学多达109名中期妊娠胎儿（11周至21周）肾上腺中类固醇、信使RNA转录物和蛋白质的观察性研究。研究设计平衡，以显示母亲吸烟的影响。使用液相色谱和质谱法定量19肾上腺内类固醇的浓度。孕烯醇酮是最丰富的类固醇，而17α-羟孕酮，硫酸脱氢表雄酮（DHEAS）和孕酮的水平也很高。所有肾上腺中均存在皮质醇，但未检出醛固酮，Δ4雄激素较低/未检出。CYP 17 A1、CYP 21 A2和CYP 11 A1均高表达，蛋白质定位于肾上腺胎儿区。HSD 3B和CYP 11B 2呈低水平表达，且主要定位于限定区。母亲吸烟改变胎儿血浆促肾上腺皮质激素（ACTH）（P = 0.052）和肾上腺内孕酮、17α-羟孕酮和16α-羟孕酮，但不改变血浆或肾上腺内皮质醇或肾上腺内DHEAS。母亲吸烟可增加胎儿肾上腺GATA 6和NR 5A 1。人胎儿肾上腺产生皮质醇，但在整个妊娠中期产生非常低水平的Δ4雄激素，并且没有检测到醛固酮。胎儿肾上腺中皮质醇的存在表明，循环胎儿ACTH的肾上腺调节仍然是妊娠中期先天性肾上腺增生的一个因素，而醛固酮的相对缺乏解释了极端早产儿中常见的盐耗性疾病。最后，母亲吸烟可能会改变胎儿肾上腺对促肾上腺皮质激素的敏感性，这可能会对产后健康产生连锁反应。本文的在线版本（10.1186/s12916-018-1009-7）包含补充材料，可供授权用户使用。
Human fetal adrenal glands are highly active and, with the placenta, regulate circulating progesterone, estrogen and corticosteroids in the fetus. At birth the adrenals are essential for neonate salt retention through secretion of aldosterone, while adequate glucocorticoids are required to prevent adrenal insufficiency. The objective of this study was to carry out the first comprehensive analysis of adrenal steroid levels and steroidogenic enzyme expression in normal second trimester human fetuses. This was an observational study of steroids, messenger RNA transcripts and proteins in adrenals from up to 109 second trimester fetuses (11 weeks to 21 weeks) at the Universities of Aberdeen and Glasgow. The study design was balanced to show effects of maternal smoking. Concentrations of 19 intra-adrenal steroids were quantified using liquid chromatography and mass spectrometry. Pregnenolone was the most abundant steroid while levels of 17α-hydroxyprogesterone, dehydroepiandrosterone sulphate (DHEAS) and progesterone were also high. Cortisol was present in all adrenals, but aldosterone was undetected and Δ4 androgens were low/undetected. CYP17A1, CYP21A2 and CYP11A1 were all highly expressed and the proteins localized to the adrenal fetal zone. There was low-level expression of HSD3B and CYP11B2, with HSD3B located mainly in the definitive zone. Maternal smoking altered fetal plasma adrenocorticotropic hormone (ACTH) (P = 0.052) and intra-adrenal progesterone, 17α-hydroxyprogesterone and 16α-hydroxyprogesterone, but not plasma or intra-adrenal cortisol, or intra-adrenal DHEAS. Fetal adrenal GATA6 and NR5A1 were increased by maternal smoking. The human fetal adrenal gland produces cortisol but very low levels of Δ4 androgens and no detectable aldosterone throughout the second trimester. The presence of cortisol in fetal adrenals suggests that adrenal regulation of circulating fetal ACTH remains a factor in development of congenital adrenal hyperplasia during the second trimester, while a relative lack of aldosterone explains the salt-wasting disorders frequently seen in extreme pre-term neonates. Finally, maternal smoking may alter fetal adrenal sensitivity to ACTH, which could have knock-on effects on post-natal health. The online version of this article (10.1186/s12916-018-1009-7) contains supplementary material, which is available to authorized users.
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DOI：
10.1016/j.reprotox.2016.05.009
发表时间：
2016-08
期刊：
Reproductive toxicology (Elmsford, N.Y.)
影响因子：
--
作者：
Huuskonen P;Amezaga MR;Bellingham M;Jones LH;Storvik M;Häkkinen M;Keski-Nisula L;Heinonen S;O'Shaughnessy PJ;Fowler PA;Pasanen M
通讯作者：
Pasanen M
影响因子：
2.9
作者：
Block T;Petrides G;Kushner H;Kalin N;Belanoff J;Schatzberg A
通讯作者：
Schatzberg A
DOI：
10.1016/0022-4731(77)90252-7
发表时间：
1977-01-01
影响因子：
4.1
作者：
MACNAUGHTON, MC;TAYLOR, T;COUTIS, JRT
通讯作者：
COUTIS, JRT
影响因子：
2.9
作者：
Fernandez, E. F.;Watterberg, K. L.
通讯作者：
Watterberg, K. L.
DOI：
10.1111/j.1471-0528.1990.tb01827.x
发表时间：
1990-05-01
期刊：
BRITISH JOURNAL OF OBSTETRICS AND GYNAECOLOGY
影响因子：
--
作者：
HILL, NCW;SELINGER, M;MACKENZIE, IZ
通讯作者：
MACKENZIE, IZ