Department of Anesthesiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Institute of Reproductive Biomedicine, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Reproduction. 2022 Dec 2;165(1):19-30. doi: 10.1530/REP-22-0136. Print 2023 Jan 1.
Glucagon-like peptide-1 stimulates stem Leydig cell development. Glucagon-like peptide-1 stimulates stem Leydig cell differentiation without affecting its proliferation.
The regulators of stem Leydig cell (SLC) development remain largely unknown. The effect of glucagon-like peptide-1 (GLP-1) on rat SLC proliferation and differentiation was investigated using a 3D tissue culture system and an ethane dimethane sulfonate (EDS)-treated in vivo LC regeneration model. RNA-seq analysis was performed to analyze pathways in which GLP-1 may be involved. GLP-1 (3 and 30 nmol/L) significantly increased medium testosterone abundances and upregulated the expression of Scarb1, Cyp11a1, and Hsd11b1. GLP-1 in vitro did not affect SLC proliferation by 5-Ethynyl-2'- deoxyuridine (EdU) incorporation assay. Intratesticular injection of GLP-1 (10 and 100 ng/testis) into the LC-depleted testis from day 14 to day 28 post-EDS significantly increased serum testosterone abundances and upregulated the expression of Cyp11a1, Hsd3b1, and Hsd11b1. It did not affect the number of HSD11B1+ and CYP11A1+ LCs. RNA-seq analysis revealed that GLP-1 upregulated several pathways, including cAMP-PKA-EPAC1 and MEK/ERK1/2. GLP-1 stimulates SLC differentiation without affecting its proliferation, showing its novel action and mechanism on rat SLC development.
胰高血糖素样肽-1 可刺激干细胞莱迪希细胞的发育。胰高血糖素样肽-1 可刺激干细胞莱迪希细胞分化，而不影响其增殖。
干细胞莱迪希细胞（SLC）发育的调节因子在很大程度上尚不清楚。本研究采用 3D 组织培养系统和乙烷二甲基磺酸（EDS）处理的体内 LC 再生模型，研究了胰高血糖素样肽-1（GLP-1）对大鼠 SLC 增殖和分化的影响。进行了 RNA-seq 分析，以分析 GLP-1 可能涉及的途径。GLP-1（3 和 30 nmol/L）可显著增加培养基中睾丸酮的含量，并上调 Scarb1、Cyp11a1 和 Hsd11b1 的表达。GLP-1 在体外通过 5-乙炔基-2'-脱氧尿苷（EdU）掺入试验不影响 SLC 增殖。从 EDS 处理后第 14 天到第 28 天，向 LC 耗竭的睾丸内注射 GLP-1（10 和 100 ng/睾丸）可显著增加血清睾丸酮含量，并上调 Cyp11a1、Hsd3b1 和 Hsd11b1 的表达。它不影响 HSD11B1+和 CYP11A1+LC 的数量。RNA-seq 分析表明，GLP-1 上调了几个途径，包括 cAMP-PKA-EPAC1 和 MEK/ERK1/2。GLP-1 刺激 SLC 分化而不影响其增殖，显示其对大鼠 SLC 发育具有新的作用和机制。
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