Classic and backdoor pathways of androgen biosynthesis in human sexual development.
Classic and backdoor pathways of androgen biosynthesis in human sexual development.
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DOI：
10.6065/apem.2244124.062
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发表时间：
2022-06
影响因子：
2.2
通讯作者：
Kim, Chan Jong
中科院分区：
文献类型：
--
作者：
Lee, Hyun Gyung;Kim, Chan Jong
基因和激素都调节着人类的性发育。虽然卵巢激素对女性外生殖器发育不是必需的，但男性的性发育需要睾丸睾酮和双氢睾酮（DHT）的作用。DHT是最活跃的内源性雄激素，由生殖器皮肤中的睾酮转化而成。这种从胆固醇到二氢睾酮的合成途径被称为传统的经典途径。最近的研究报道了绕过胎儿睾丸睾酮形成DHT的另一种途径（“后门”）。这一替代途径在P450c21缺乏症、多囊卵巢综合征和P450氧化还原酶缺乏症引起的先天性肾上腺增生等人类高雄激素性疾病中起着至关重要的作用。此外，编码3α-还原酶的基因AKR1C2和AKR1C4的突变与性发育障碍有关，这表明正常的人类男性性发育都需要经典途径和后门途径。最近，雄酮被发现是人类后门途径的主要雄激素。后门途径特有的雄酮和甾体底物主要存在于胎盘、肝脏和肾上腺中，而不是睾丸中。这些发现对于理解人类的性发展至关重要。
Both genes and hormones regulate human sexual development. Although ovarian hormones are not essential for female external genitalia development, male sexual development requires the action of testicular testosterone and dihydrotestosterone (DHT). DHT is the most active endogenous androgen formed by the conversion of testosterone in genital skin. This synthesis route from cholesterol to DHT is called the conventional classic pathway. Recent investigations have reported an alternative ("backdoor") route for DHT formation that bypasses fetal testicular testosterone. This alternative route plays a crucial role in human hyperandrogenic disorders like congenital adrenal hyperplasia caused by P450c21 deficiency, polycystic ovary syndrome, and P450 oxidoreductase deficiency. In addition, mutations in AKR1C2 and AKR1C4, genes encoding 3α-reductases, have been implicated in disorders of sexual development, indicating that both the classic and backdoor routes are required for normal human male sexual development. More recently, androsterone was found to be the primary androgen of the human backdoor route. Androsterone and steroidal substrates specific to the backdoor route are predominantly found in the placenta, liver, and adrenal glands rather than in the testes. These findings are essential to understanding human sexual development.
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DOI：
10.1007/s004290050243
发表时间：
1999-05-01
期刊：
ANATOMY AND EMBRYOLOGY
影响因子：
--
作者：
Butler, CM;Shaw, G;Renfree, MB
通讯作者：
Renfree, MB
影响因子：
5.8
作者：
Fukami, Maki;Nishimura, Gen;Ogata, Tsutomu
通讯作者：
Ogata, Tsutomu
影响因子：
44.5
作者：
Gidlof, Sebastian;Falhammar, Henrik;Nordenstrom, Anna
通讯作者：
Nordenstrom, Anna
影响因子：
168.9
作者：
Arlt, W;Walker, EA;Shackleton, CHL
通讯作者：
Shackleton, CHL
影响因子：
5.8
作者：
Fukami, M;Horikawa, R;Ogata, T
通讯作者：
Ogata, T