Androgen biosynthesis during minipuberty favors the backdoor pathway over the classic pathway: Insights into enzyme activities and steroid fluxes in healthy infants during the first year of life from the urinary steroid metabolome
Androgen biosynthesis during minipuberty favors the backdoor pathway over the classic pathway: Insights into enzyme activities and steroid fluxes in healthy infants during the first year of life from the urinary steroid metabolome
复制标题
DOI：
10.1016/j.jsbmb.2016.07.009
复制
发表时间：
2017-01-01
影响因子：
4.1
通讯作者：
Fluck, Christa E.
中科院分区：
文献类型：
--
作者：
Dhayat, Nasser A.;Dick, Bernhard;Fluck, Christa E.
类固醇的配置文件从产前到产后的生活显着变化。最近，一个新的后门途径的雄激素生物合成已被发现。然而，其作用仍然难以捉摸。因此，我们研究了从出生到一岁的雄激素产生，重点是青春期不足和通过后门途径产生雄激素。此外，我们评估了特定类固醇酶活性在生命早期的发展。为此，我们收集了43名健康新生儿（22名女性）从出生到一岁的13个时间点的尿布尿液标本，并在室内进行了67种类固醇代谢产物的GC MS类固醇分析。通过经典途径和后门途径分析雄激素产生的数据，并计算类固醇酶活性的诊断比率。分析显示，在青春期初期，男孩的雄激素产生远高于女孩（例如雄激素（An）），主要来源于睾丸（An（男孩）-An（女孩）），并主要使用替代后门途径（An/Et; Delta 5 < Delta 4裂合酶活性）。类固醇酶活性的建模显示，21-，11-，17-羟化酶和P450氧化还原酶活性以及3 β-羟基类固醇脱氢酶，11 β-羟化酶1/2型和5 α-还原酶活性的年龄相关的影响。21-羟化酶和5 α-还原酶的活性与性别有关。总体而言，我们的研究表明，青春期小发育期间的雄激素生物合成有利于后门途径而不是经典途径。酶活性的特定诊断比率的计算似乎允许从尿类固醇代谢组诊断特定的类固醇疾病。(C)2016爱思唯尔有限公司版权所有
The steroid profile changes dramatically from prenatal to postnatal life. Recently, a novel backdoor pathway for androgen biosynthesis has been discovered. However, its role remains elusive. Therefore, we investigated androgen production from birth to one year of life with a focus on minipuberty and on production of androgens through the backdoor pathway. Additionally, we assessed the development of the specific steroid enzyme activities in early life. To do so, we collected urine specimens from diapers in 43 healthy newborns (22 females) at 13 time points from birth to one year of age in an ambulatory setting, and performed in house GC MS steroid profiling for 67 steroid metabolites. Data were analyzed for androgen production through the classic and backdoor pathway and calculations of diagnostic ratios for steroid enzyme activities were performed. Analysis revealed that during minipuberty androgen production is much higher in boys than in girls (e.g. androsterone (An)), originates largely from the testis, (An(boys)-An(girls)) and uses predominantly the alternative backdoor pathway (An/Et; Delta 5 < Delta 4 lyase activity). Modelling of steroid enzyme activities showed age-related effects for 21-, 11-, 17-hydroxylase and P450 oxidoreductase activities as well as 3 p-hydroxysteroid dehydrogenase, 11 beta-hydroxylase type 1/2 and 5 alpha-reductase activities. Sex-related characteristics were found for 21-hydroxylase and 5 alpha-reductase activities. Overall, our study shows that androgen biosynthesis during minipuberty favors the backdoor pathway over the classic pathway. Calculations of specific diagnostic ratios for enzyme activities seem to allow the diagnosis of specific steroid disorders from the urinary steroid metabolome. (C) 2016 Elsevier Ltd. All rights reserved.