Hydroxysteroid (17β) dehydrogenase 1 expressed by Sertoli cells contributes to steroid synthesis and is required for male fertility
Hydroxysteroid (17β) dehydrogenase 1 expressed by Sertoli cells contributes to steroid synthesis and is required for male fertility
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DOI：
10.1096/fj.201700921r
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发表时间：
2018-06-01
期刊：
影响因子：
4.8
通讯作者：
Poutanen, Matti
中科院分区：
文献类型：
--
作者：
Hakkarainen, Janne;Zhang, Fu-Ping;Poutanen, Matti
垂体促性腺激素和睾酮是精子发生的主要激素调节剂，但已知雌二醇也在该过程中发挥作用。睾丸中的激素反应部分由支持细胞介导，支持细胞为分化雄性生殖细胞提供营养和物理支持。羟基类固醇（17 β）脱氢酶1（HSD 17 B1）是一种类固醇生成酶，特别是催化低效力的17酮类固醇转化为高效力的17 β-羟基类固醇。在这项研究中，我们表明，Hsd 17 B1是高度表达的胎儿和新生小鼠的支持细胞，和HSD 17 B1基因敲除男性目前与破坏精子发生的重大缺陷，特别是在头部形状的精子细胞延长。在HSD 17 B1敲除小鼠中，支持细胞和生殖细胞之间的细胞-细胞连接被破坏。这导致了生精上皮中伸长精子细胞方向的并发症，精子产量减少，精子形态异常。我们还表明，支持细胞表达的HSD 17 B1参与睾丸类固醇合成，证明了在睾丸间质细胞中的补偿性上调HSD 17 B3。这些结果揭示了HSD 17 B1在控制精子发生和男性生育力中的新作用，并且支持细胞显著有助于睾丸中的类固醇合成。
The pituitary gonadotrophins and testosterone are the main hormonal regulators of spermatogenesis, but estradiol is also known to play a role in the process. The hormonal responses in the testis are partially mediated by somatic Sertoli cells that provide nutritional and physical support for differentiating male germ cells. Hydroxysteroid (17 beta) dehydrogenase 1 (HSD17B1) is a steroidogenic enzyme that especially catalyzes the conversion of low potent 17keto-steroids to highly potent 17 beta-hydroxysteroids. In this study, we show that Hsd17b1 is highly expressed in Sertoli cells of fetal and newborn mice, and HSD17B1 knockout males present with disrupted spermatogenesis with major defects, particularly in the head shape of elongating spermatids. The cell-cell junctions between Sertoli cells and germ cells were disrupted in the HSD17B1 knockout mice. This resulted in complications in the orientation of elongating spermatids in the seminiferous epithelium, reduced sperm production, and morphologically abnormal spermatozoa. We also showed that the Sertoli cell-expressed HSD17B1 participates in testicular steroid synthesis, evidenced by a compensatory up-regulation of HSD17B3 in Leydig cells. These results revealed a novel role for HSD17B1 in the control of spermatogenesis and male fertility, and that Sertoli cells significantly contribute to steroid synthesis in the testis.