Androgenic potential of human fetal adrenals at the end of the first trimester.
Androgenic potential of human fetal adrenals at the end of the first trimester.
复制标题
DOI：
10.1530/ec-17-0085
复制
发表时间：
2017-08
影响因子：
2.9
通讯作者：
Svechnikov K
中科院分区：
文献类型：
--
作者：
Savchuk I;Morvan ML;Antignac JP;Gemzell-Danielsson K;Le Bizec B;Söder O;Svechnikov K
人胎儿肾上腺（HFA）在孕早期类固醇合成的发生研究很少。一个尚未解决的问题是HFA通过常规和/或后门途径在孕早期结束时产生强效雄激素DHT的能力，此时雄激素反应器官发育。我们的目的是探讨孕9-12周时HFA中类固醇生成和类固醇生成酶和转录因子的表达，重点是其雄激素潜力。通过气相色谱/质谱法分析HFA中的类固醇。通过qPCR、自动蛋白质印迹和免疫组织化学研究了GW 9 -12处HFA中类固醇生成酶和转录因子的表达。我们证明，在GW 9 -12期间，HFA产生的甾体激素的β 5，β 4和后门途径的生物合成的DHT，虽然后者是有限的生产17α-OH-二氢孕酮，雄甾酮和雄甾烷二酮没有进一步转化为DHT。在HFA中鉴定的唯一雄激素是睾酮和雄酮，雄酮是双氢睾酮生物合成的前体。我们还观察到在HFA中GW 11 -12的CYP 17 A1水平较高，但3β HSD 2表达较低。CYP 17 A1水平升高与SF-1和加塔-6表达增加相关。总而言之，我们的数据表明，在分析的这些类固醇中，在GW 9 -12由HFA直接产生的唯一有效雄激素是睾酮。HFA中类固醇合成的开始是一个复杂的过程，其受相关转录因子的协调作用调节。
The onset of steroidogenesis in human fetal adrenal glands (HFA) during the first trimester is poorly investigated. An unresolved question is the capacity of the HFA to produce potent androgen DHT via conventional and/or the backdoor pathway(s) at the end of first trimester, when androgen-responsive organs are developed. Our aim was to explore steroidogenesis and the expression of steroidogenic enzymes and transcription factors in HFA at gestational weeks (GW) 9–12 with focus on their androgenic potential. Steroids in the HFA were analyzed by gas chromatography/mass spectrometry. The expression of steroidogenic enzymes and transcription factors in the HFA at GW9–12 was investigated by qPCR, automated Western blotting and immunohistochemistry. We demonstrated that during GW9–12 HFA produced steroids of the ∆5, ∆4 and the backdoor pathways of the biosynthesis of DHT, though the latter was limited to production of 17α-OH-dihydroprogesterone, androsterone and androstanedione without further conversion to DHT. The only androgens identified in the HFA were testosterone and androsterone, a precursor in the biosynthesis of DHT. We also observed higher levels of CYP17A1 but low expression of 3βHSD2 at GW11–12 in the HFA. Elevated levels of CYP17A1 were associated with an increased expression of SF-1 and GATA-6. Altogether, our data demonstrate that of those steroids analyzed, the only potent androgen directly produced by the HFA at GW9–12 was testosterone. The onset of steroidogenesis in the HFA is a complex process that is regulated by the coordinated action of related transcription factors.