Department of Biomedicine and Prevention, University of Rome Tor Vergata, 00133, Rome, Italy.
Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, 00133, Rome, Italy.
Sci Rep. 2017 Jun 14;7(1):3469. doi: 10.1038/s41598-017-02018-2.
Cytochrome P450-aromatase catalyzes estrogen biosynthesis from C steroids. In the testis, Sertoli cells express P450-aromatase and represent the primary source of estrogen during prepuberal age. This study focused on the effect of simulated microgravity (SM) on aromatase expression in primary mouse Sertoli cells. When cultured in Rotary Cell Culture System (RCCS), Sertoli cells, formed multicellular three dimensional spheroids (3D). Biological properties were first analyzed in terms of viability, cell cycle, expression of cytoskeletal components and growth factors in comparison to Sertoli cells cultured in spheroids at unit gravity (G). SM did not affect cell viability and proliferation, nor expression of the main cytoskeleton proteins and of growth factors like Kit Ligand (KL) and glial derived neurotrophic factor (GDNF). On the other hand, SM caused a strong increase in P450 aromatase mRNA and protein expression. Interestingly, P450-aromatase was no more inducible by 8-Br-cAMP. The presence of a functional aromatase was confirmed by enrichment of 17β-estradiol released in the medium by androgen precursors. We concluded that SM causes a significant upregulation of aromatase gene expression in Sertoli cells, leading to a consequent increase in 17β-estradiol secretion. High level of 17β-estradiol in the testis could have potentially adverse effects on male fertility and testicular cancer.
细胞色素 P450 芳香化酶催化 C 类固醇合成雌激素。在睾丸中,支持细胞表达 P450 芳香化酶,是青春期前雌激素的主要来源。本研究聚焦于模拟微重力(SM)对原代小鼠支持细胞芳香化酶表达的影响。当在旋转细胞培养系统(RCCS)中培养时,支持细胞形成多细胞三维球体(3D)。与在重力(G)下培养的球体中的支持细胞相比,首先从活力、细胞周期、细胞骨架成分和生长因子的表达等方面分析了其生物学特性。SM 不影响细胞活力和增殖,也不影响主要细胞骨架蛋白和生长因子如 Kit 配体(KL)和胶质衍生神经营养因子(GDNF)的表达。另一方面,SM 导致 P450 芳香化酶 mRNA 和蛋白表达的强烈增加。有趣的是,8-Br-cAMP 不再诱导 P450 芳香化酶。雄激素前体释放到培养基中的 17β-雌二醇的富集证实了芳香酶的存在。我们得出结论,SM 导致支持细胞中芳香化酶基因表达显著上调,从而导致 17β-雌二醇分泌增加。睾丸中高水平的 17β-雌二醇可能对男性生育力和睾丸癌产生潜在的不利影响。