Foetal virilisation caused by overproduction of non-aromatisable 11-oxygenated C19 steroids in maternal adrenal tumour
Foetal virilisation caused by overproduction of non-aromatisable 11-oxygenated C19 steroids in maternal adrenal tumour
复制标题
母体肾上腺肿瘤中不可芳香化的 11-氧化 C19 类固醇过量产生导致胎儿男性化
DOI：
10.1093/humrep/deaa221
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发表时间：
2020
影响因子：
6.1
通讯作者：
Fukami Maki
中科院分区：
文献类型：
--
作者：
Nagasaki Keisuke;Takase Kaoru;Numakura Chikahiko;Homma Keiko;Hasegawa Tomonobu;Fukami Maki
人们普遍认为，孕妇的肾上腺肿瘤和卵巢黄体瘤通过过量分泌睾酮和/或雄烯二酮导致女性胎儿阳刚之气。然而，这一概念提出了一个基本问题，即这些经典的雄激素是如何通过胎盘而不被芳香化酶转化为雌激素的。在这里，我们报告了一例母体肾上腺肿瘤，其中11-氧合C19类固醇（11ox C19）的过量产生，在人类中新发现的非芳香雄激素，导致胎儿男性化。女性先证者在出生时表现出严重男性化的外生殖器。母亲表现出多毛、高血糖和高血压，并被诊断为肾上腺肿瘤。母亲接受了全面的类固醇测量。血清11ox - c19水平明显升高。相比之下，睾酮和雄烯二酮水平保持在正常范围内，常规和后门雄激素途径中的大多数其他类固醇水平正常或仅轻度升高。肿瘤切除后，11ox - c19水平明显降低。这些结果提供了第一个证据，证明11ox c19可以在肾上腺腺瘤中合成，并且由于它们的非芳香性，可以通过胎盘屏障导致胎儿阳化。这些发现突出了这些新指定的雄激素在人类中的独特致病性。
It is widely believed that adrenal tumours and ovarian luteomas in pregnant women cause virilisation of female foetuses through overproduction of testosterone and/or androstenedione. However, this notion raises a fundamental question as to how these classic androgens pass through the placenta without being converted by aromatase into oestrogens. Here, we report a case of maternal adrenal tumour, in which overproduction of 11-oxygenated C19 steroids (11ox C19s), newly characterised non-aromatisable androgens in humans, caused foetal virilisation. The female proband presented with severely virilised external genitalia at birth. The mother exhibited hirsutism, hyperglycaemia and hypertension and was diagnosed as having adrenal tumour. The mother was subjected to comprehensive steroid measurement. Serum levels of 11ox C19s were markedly elevated. In contrast, testosterone and androstenedione levels remained within the normal range, and levels of most other steroids in the conventional and backdoor androgenic pathways were normal or only mildly elevated. After tumour removal, levels of 11ox C19s were markedly reduced. These results provide the first evidence that 11ox C19s can be synthesised in adrenal adenomas and, due to their non-aromatisable nature, can pass through the placental barrier to cause foetal virilisation. These findings highlight a unique pathogenic property of these newly specified androgens in humans.