Androgens in Congenital Adrenal Hyperplasia.

2区 医学 Q2 Medicine Frontiers of Hormone Research Pub Date : 2019-01-01 DOI:10.1159/000494903
D. Pignatelli, S. Pereira, R. Pasquali
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引用次数: 16

Abstract

Congenital Adrenal Hyperplasias (CAH) are genetic diseases transmitted in an autosomal recessive way and these diseases affect many aspects of human health. The majority of CAH cases is due to a deficiency in 21-hydroxylase as a result of the existence of mutations in both alleles of the CYP21A2 gene. Since the identification of mild, non-classic forms of this disease, CAH has been recognized to be one of the most common genetic diseases in human beings. This disease is generally associated with elevated secretion of androgens, sometimes resulting in virilizing syndromes, including genital ambiguity, precocious puberty in both sexes, or milder syndromes of androgen excess like precocious pubarche or the occurrence of hirsutism and oligomenorrhea in women. Accumulating precursors like 17-hydroxypregnenolone and 17-hydroxyprogesterone (17OHP) are directed to the synthesis of androgens through the enzyme 17-hydroxylase/17,20 lyase leading to the production of dehydroepiandrosterone that is then converted to testosterone and dihydrotestosterone (DHT) at the gonads and at other peripheral tissues. 17OHP, the hallmark of 21-hydroxylase deficiency, can be converted to androstenedione (in a low efficiency molecular process) but can also be converted to DHT through an alternative pathway that becomes active due to the large amounts of accumulated 17OHP - the backdoor pathway. Another important pathway that becomes significant in this disease is the 11-oxyandrogens pathway through which androstenedione is converted to 11β-hydroxyandrostenedione at the adrenal and from there to 11-ketotestosterone and 11-ketoDHT. The elevated androgens levels affect the hypothalamic-pituitary-gonadal axis and, in some cases, the ovary resulting in chronic anovulation and infertility.
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先天性肾上腺增生中的雄激素。
先天性肾上腺皮质增生症(CAH)是一种常染色体隐性遗传的遗传病,影响着人类健康的许多方面。大多数CAH病例是由于CYP21A2基因的两个等位基因存在突变而导致21-羟化酶缺乏。由于发现了这种疾病的轻度、非经典形式,CAH已被认为是人类最常见的遗传性疾病之一。这种疾病通常与雄激素分泌升高有关,有时导致阳刚综合征,包括生殖器模糊、两性性早熟,或雄激素过量的较轻综合征,如阴毛早熟或女性多毛和少月经的发生。积累的前体如17-羟基孕烯醇酮和17-羟基孕酮(17OHP)通过17-羟化酶/17,20裂解酶直接合成雄激素,产生脱氢表雄酮,然后在性腺和其他外周组织转化为睾酮和双氢睾酮(DHT)。17OHP是21-羟化酶缺乏症的标志,它可以转化为雄烯二酮(在一个低效率的分子过程中),但也可以通过另一种途径转化为二氢睾酮,这种途径由于积累了大量的17OHP而变得活跃——后门途径。在这种疾病中另一个重要的途径是11-氧雄激素途径雄烯二酮通过它在肾上腺转化为11β-羟基雄烯二酮然后再转化为11-酮睾酮和11-酮二氢睾酮。雄激素水平升高会影响下丘脑-垂体-性腺轴,在某些情况下,还会影响卵巢,导致慢性无排卵和不孕。
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来源期刊
Frontiers of Hormone Research
Frontiers of Hormone Research 医学-内分泌学与代谢
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期刊介绍: A series of integrated overviews on cutting-edge topics New sophisticated technologies and methodological approaches in diagnostics and therapeutics have led to significant improvements in identifying and characterizing an increasing number of medical conditions, which is particularly true for all aspects of endocrine and metabolic dysfunctions. Novel insights in endocrine physiology and pathophysiology allow for new perspectives in clinical management and thus lead to the development of molecular, personalized treatments. In view of this, the active interplay between basic scientists and clinicians has become fundamental, both to provide patients with the most appropriate care and to advance future research.
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