Department of Neuroendocrinology, ICMR-National Institute for Research in Reproductive Health, Mumbai, India.
Department of Neuroendocrinology, ICMR-National Institute for Research in Reproductive Health, Mumbai, India.
J Steroid Biochem Mol Biol. 2021 Jul;211:105898. doi: 10.1016/j.jsbmb.2021.105898. Epub 2021 Apr 9.
Optimal functioning of Sertoli cells is crucial for spermatogenesis which is under tight regulation of sex hormones, estrogen and androgen. Adult rat Sertoli cells expresses estrogen receptor beta (ERβ) and androgen receptor (AR), both of which regulate gene transcription by binding to the DNA. The present study is aimed to acquire a genome-wide map of estrogen- and androgen-regulated genes in adult Sertoli cells. ChIP-Seq was performed for ERβ and AR in Sertoli cells under physiological conditions. 30,859 peaks in ERβ and 9,594 peaks in AR were identified with a fold enrichment >2 fold. Pathway analysis for the genes revealed metabolic pathways to be significantly enriched. Since Sertoli cells have supportive functions and provide energy substrates to germ cells during spermatogenesis, significantly enriched metabolic pathways were explored further. Peaks of the genes involved in lipid metabolism, like fatty acid, glyceride, leucine, and sphingosine metabolism were validated. Motif analysis confirmed the presence of estrogen- and androgen-response elements (EREs and AREs). Moreover, transcript levels of enzymes involved in the lipid metabolic pathways were significantly altered in cultured Sertoli cells treated with estrogen and androgen receptor agonists, demonstrating functional significance of these binding sites. This study elucidates a mechanism by which sex hormones regulate lipid metabolism in Sertoli cells by transcriptionally controlling the expression of these genes, thereby shedding light on the roles of these hormones in male fertility.
支持细胞的最佳功能对于精子发生至关重要，而精子发生受到性激素、雌激素和雄激素的严格调节。成年大鼠支持细胞表达雌激素受体β（ERβ）和雄激素受体（AR），两者均可通过与 DNA 结合来调节基因转录。本研究旨在获得成年支持细胞中雌激素和雄激素调节基因的全基因组图谱。在生理条件下，对支持细胞中的 ERβ 和 AR 进行了 ChIP-Seq 分析。在 ERβ 中有 30859 个峰，在 AR 中有 9594 个峰，富集倍数>2 倍。对基因的通路分析表明代谢途径显著富集。由于支持细胞在精子发生过程中具有支持功能，并为精细胞提供能量底物，因此进一步探索了显著富集的代谢途径。验证了参与脂质代谢的基因（如脂肪酸、甘油酯、亮氨酸和鞘氨醇代谢）的峰。基序分析证实了雌激素和雄激素反应元件（EREs 和 AREs）的存在。此外，用雌激素和雄激素受体激动剂处理的培养支持细胞中参与脂质代谢途径的酶的转录本水平发生了显著改变，这表明这些结合位点具有功能意义。这项研究阐明了性激素通过转录控制这些基因的表达来调节支持细胞中脂质代谢的机制，从而揭示了这些激素在男性生育力中的作用。
