Joint Laboratory of Modern Agricultural Technology International Cooperation, Ministry of Education, Jilin Agricultural University, Changchun 130118, China; Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, China.
Joint Laboratory of Modern Agricultural Technology International Cooperation, Ministry of Education, Jilin Agricultural University, Changchun 130118, China; Key Laboratory of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, Changchun 130118, China.
Gene. 2020 Jul 15;747:144672. doi: 10.1016/j.gene.2020.144672. Epub 2020 Apr 16.
Brain and muscle Arnt-like protein-1 (BMAL1) is a clock gene that plays an important role in hormone secretion and apoptosis, but its effect on Leydig cells is unidentified. Here the role of BMAL1 in apoptosis and testosterone secretion in TM3 Leydig cell line were investigated by inhibiting its expression using small interfering RNA (siRNA). Results showed that BMAL1 knockdown promoted the apoptosis of Leydig cells and expression of (BCL2 associated X) BAX mRNA and protein, and reduced the expression of (B-cell lymphoma-2) BCL-2 mRNA and protein. BMAL1 inhibition resulted in decreased testosterone secretion and reduced expression of key genes during hormone synthesis, specifically steroidogenic acute regulatory protein (STAR), cytochrome P450 family 11 subfamily A member 1 (CYP11A1), and 3β-hydroxysteroid dehydrogenase (3β-HSD). In addition, BMAL1 knockdown reduced the expression of phosphorylated p85 and AKT as confirmed by western blot. In conclusion, BMAL1 may affect testosterone secretion and apoptosis in mouse Leydig cells through regulation of the PI3K/AKT signaling pathway.
脑和肌肉 ARNT 样蛋白 1（BMAL1）是一种时钟基因，在激素分泌和细胞凋亡中发挥重要作用，但它对睾丸间质细胞的作用尚不清楚。本研究通过小干扰 RNA（siRNA）抑制其表达，探讨了 BMAL1 在 TM3 睾丸间质细胞系中的凋亡和睾酮分泌中的作用。结果表明，BMAL1 敲低促进了睾丸间质细胞的凋亡以及 BAX mRNA 和蛋白的表达，并降低了 BCL-2 mRNA 和蛋白的表达。BMAL1 抑制导致睾酮分泌减少和激素合成过程中关键基因的表达降低，特别是类固醇急性调节蛋白（STAR）、细胞色素 P450 家族 11 亚家族 A 成员 1（CYP11A1）和 3β-羟甾体脱氢酶（3β-HSD）。此外，Western blot 证实 BMAL1 敲低降低了磷酸化 p85 和 AKT 的表达。综上所述，BMAL1 可能通过调节 PI3K/AKT 信号通路影响小鼠睾丸间质细胞的睾酮分泌和凋亡。
