Possible testosterone redundancy for 5α-dihydrotestosterone in the masculinization of mouse external genitalia.
Possible testosterone redundancy for 5α-dihydrotestosterone in the masculinization of mouse external genitalia.
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DOI：
10.1538/expanim.22-0038
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发表时间：
2022-11-10
影响因子：
2.4
通讯作者：
Hara, Isao
中科院分区：
文献类型：
--
作者：
Ueda, Yuko;Suzuki, Kentaro;Kajimoto, Mizuki;Fujimoto, Kota;Mahendroo, Mala;Ema, Masatsugu;Yamada, Gen;Hara, Isao
关键词：
胚胎外生殖器（eExG）发育为男性特征性结构，如尿道和阴茎勃起组织，依赖于5α-二氢睾酮（DHT）。虽然阴茎海绵体（CC）是众所周知的成人勃起功能所必需的，但其发育过程及其对DHT的依赖性尚不清楚。为了揭示小鼠CC从胚胎期开始的二态形成，我们首先分析了在发育的外生殖器中通过其表达的蛋白质血管内皮生长因子受体-2（FLK 1）的产生（下文称为“FLK 1的表达”）以及α-平滑肌肌动蛋白（ACTA 2）和1型胶原蛋白（COL 1A 1）的表达。由SRD 5A 2基因编码的5-α还原酶2型被认为是男性性分化的关键酶，因为它在局部泌尿生殖器官中将睾酮（T）转化为DHT。事实上，SRD 5A 2突变导致DHT合成减少，从而导致不同程度的男性化人类外生殖器（ExG）。我们进一步研究了SRD 5A 2在小鼠CC形成过程中的表达谱。我们观察到SRD 5A 2在CC的平滑肌中表达。为了确定SRD 5A 2在CC形成中的作用，我们分析了雄性Srd 5a 2 KO小鼠中勃起组织的形成，并通过液相色谱-串联质谱法（LC-MS/MS）测量了ExG中雄激素的水平。有趣的是，在雄性Srd 5a 2 KO小鼠的CC中没有明显的缺陷，可能是由于T水平增加。目前的研究表明雄激素在CC发展中可能具有冗余功能。
The development of embryonic external genitalia (eExG) into characteristic male structures, such as urethra and penile erectile tissues, depends on 5α-dihydrotestosterone (DHT). Although the corpus cavernosum (CC) is well known as essential for erectile function in adults, its developmental process and its dependency on DHT have been unknown. To reveal the dimorphic formation of the murine CC from the embryonic stage, we first analyzed the production of the protein vascular endothelial growth factor receptor-2 (FLK1) via its expression (hereinafter referred as “expression of FLK1”) and the expression of alpha-smooth muscle actin (ACTA2) and collagen type 1 (COL1A1) in developing external genitalia. The 5-α reductase type 2 encoded by the SRD5A2 gene has been suggested to be a crucial enzyme for male sexual differentiation, as it converts testosterone (T) into DHT in the local urogenital organs. In fact, SRD5A2 mutation results in decreased synthesis of DHT, which leads to various degrees of masculinized human external genitalia (ExG). We further investigated the expression profile of SRD5A2 during the formation of the murine CC. We observed that SRD5A2 was expressed in smooth muscle of the CC. To determine the role of SRD5A2 in CC formation, we analyzed the formation of erectile tissue in the male Srd5a2 KO mice and measured the levels of androgens in the ExG by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Intriguingly, there were no obvious defects in the CCs of male Srd5a2 KO mice, possibly due to increased T levels. The current study suggests possible redundant functions of androgens in CC development.
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影响因子：
3.4
作者：
Hashimoto D;Kajimoto M;Ueda Y;Hyuga T;Fujimoto K;Inoue S;Suzuki K;Kataoka T;Kimura K;Yamada G
通讯作者：
Yamada G
影响因子：
5
作者：
Cao, Zhimin (Tim);Botelho, Julianne Cook;Vesper, Hubert
通讯作者：
Vesper, Hubert
影响因子：
64.8
作者：
ANDERSSON, S;BERMAN, DM;RUSSELL, DW
通讯作者：
RUSSELL, DW
影响因子：
6.6
作者：
Johannes, CB;Araujo, AB;McKinlay, JB
通讯作者：
McKinlay, JB
影响因子：
2.8
作者：
Wen, Juan;Zhao, Yuan;Li, Jinghe;Weng, Chunyan;Cai, Jingjing;Yang, Kan;Yuan, Hong;Imperato-McGinley, Julianne;Zhu, Yuan-Shan
通讯作者：
Zhu, Yuan-Shan