Department of Urology, Shanghai Tenth People's Hospital, Tongji University, Shanghai, China.
Department of Urology, Yijishan Hospital, Wannan Medical College, Wuhu, Anhui, China.
BMC Pharmacol Toxicol. 2019 May 27;20(1):32. doi: 10.1186/s40360-019-0312-z.
It is an established fact that excess of glucocorticoids could cause the harmful effects, such as suppression on the male reproduction. Although glucocorticoids pharmacologically inhibit the Leydig cell function, their roles in Leydig cell development are unclear. Therefore, the present study was designed to investigate effects of synthetic glucocorticoid dexamethasone (DEX) on rat stem Leydig cell proliferation and differentiation.
Male Sprague-Dawley rats received a single intraperitoneal injection of 75 mg/kg EDS to eliminate Leydig cells and an in vitro culture system of the seminiferous tubules was established from Leydig cell-depleted testis. Using basal medium and Leydig cell differentiation-inducing medium (LIM) in the culture system, we examined the effects of DEX (0-100 nM) on the proliferation and differentiation of the stem Leydig cells in vitro, respectively.
Results showed that LIM is a good agent to induce stem Leydig cell differentiation into Leydig cells that produce testosterone in vitro. DEX inhibited the differentiation of stem Leydig cells by reducing the expression levels of Cyp17a1 and Scarb1 and that NR3C1 antagonist RU38486 reversed the DEX-mediated effects. However, DEX are not involved with the proliferation of stem Leydig cells.
DEX suppressed the differentiation of rat Leydig cells in vitro and glucocorticoid-induced effects acted through NR3C1. This suppression partially targets on Cyp17a1 and Scarb1 gene expression.
过量的糖皮质激素会产生有害作用，如抑制男性生殖功能，这是已被证实的事实。虽然糖皮质激素在药理学上抑制了间质细胞的功能，但它们在间质细胞发育中的作用尚不清楚。因此，本研究旨在探讨合成糖皮质激素地塞米松（DEX）对大鼠间质干细胞增殖和分化的影响。
雄性 Sprague-Dawley 大鼠单次腹腔注射 75mg/kg 的 EDS 以消除间质细胞，并从去间质细胞睾丸建立生精小管体外培养系统。在培养系统中使用基础培养基和间质细胞分化诱导培养基（LIM），分别研究 DEX（0-100nM）对间质干细胞体外增殖和分化的影响。
结果表明，LIM 是一种很好的诱导间质干细胞向体外产生睾酮的间质细胞分化的试剂。DEX 通过降低 Cyp17a1 和 Scarb1 的表达水平来抑制间质干细胞的分化，而 NR3C1 拮抗剂 RU38486 逆转了 DEX 的介导作用。然而，DEX 不参与间质干细胞的增殖。
DEX 抑制了大鼠间质细胞的体外分化，糖皮质激素诱导的作用通过 NR3C1 发挥作用。这种抑制作用部分针对 Cyp17a1 和 Scarb1 基因的表达。
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