Institute of Biomedicine, University of Turku, Turku, Finland.
Cell Biology-Anatomy III, Biomedical Center (BMC), Ludwig-Maximilians-Universität München, Martinsried, Germany.
FASEB J. 2018 Jun;32(6):3229-3241. doi: 10.1096/fj.201700921R. Epub 2018 Jan 24.
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 (17β) dehydrogenase 1 (HSD17B1) is a steroidogenic enzyme that especially catalyzes the conversion of low potent 17keto-steroids to highly potent 17β-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.-Hakkarainen, J., Zhang, F.-P., Jokela, H., Mayerhofer, A., Behr, R., Cisneros-Montalvo, S., Nurmio, M., Toppari, J., Ohlsson, C., Kotaja, N., Sipilä, P., Poutanen, M. Hydroxysteroid (17β) dehydrogenase 1 expressed by Sertoli cells contributes to steroid synthesis and is required for male fertility.
垂体促性腺激素和睾酮是精子发生的主要激素调节剂，但雌二醇也被认为在该过程中发挥作用。睾丸中的激素反应部分由体细胞支持细胞介导，这些细胞为分化的雄性生殖细胞提供营养和物理支持。羟甾类（17β）脱氢酶 1（HSD17B1）是一种甾体生成酶，特别催化低活性 17-酮甾体转化为高活性 17β-羟甾体。在这项研究中，我们表明 Hsd17b1 在胎儿和新生小鼠的支持细胞中高度表达，并且 HSD17B1 敲除雄性表现出破坏的精子发生，主要缺陷是伸长精子头部形状。支持细胞和生殖细胞之间的细胞-细胞连接在 HSD17B1 敲除小鼠中被破坏。这导致生精上皮中伸长精子的取向复杂化，精子生成减少，并且精子形态异常。我们还表明，Sertoli 细胞表达的 HSD17B1 参与睾丸类固醇合成，这由 Leydig 细胞中 HSD17B3 的代偿性上调证明。这些结果揭示了 HSD17B1 在精子发生和男性生育力控制中的新作用，并且支持细胞对睾丸类固醇合成有重大贡献。-Hakkarainen，J.，Zhang，F.-P.，Jokela，H.，Mayerhofer，A.，Behr，R.，Cisneros-Montalvo，S.，Nurmio，M.，Toppari，J.，Ohlsson，C.，Kotaja，N.，Sipilä，P.，Poutanen，M. 由支持细胞表达的羟甾类（17β）脱氢酶 1有助于类固醇合成，是雄性生育所必需的。
