Laboratory of Laboratory Animal Science, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.
Safety Assessment Department, Kumamoto Laboratories, Mediford Corporation, Tokyo, Japan.
J Vet Med Sci. 2024 May 25;86(5):555-562. doi: 10.1292/jvms.24-0042. Epub 2024 Apr 1.
Glucagon-like peptide-1 (GLP-1) is an incretin released into the gastrointestinal tract after food ingestion, and stimulates insulin secretion from the beta cells of the pancreatic islets. Incretins have recently been reported to have extrapancreatic actions, and they are anticipated to have potential efficacy for conditions such as male infertility as well as diabetes. However, the effects of incretins on male reproductive function remain unclear. In this study, GLP-1 receptor expression and the effects of GLP-1 on spermatogenesis-associated genes were investigated using mouse testes and testis-derived cultured cell lines. Glp1r mRNA and GLP-1 protein were expressed in mouse testes at levels comparable to or greater than those in positive control adipose tissue, and the liver and intestine, and also in a Sertoli cell line (TM4) and a Leydig cell line (MA-10) as well as the GC-1 spg and GC-2 spd (ts) germ cell lines. TM4 cells treated with the GLP-1 receptor agonist exenatide showed transiently and significantly upregulated Kitl, Pdgfa, and Glp1r mRNA expression. Furthermore, at 1 hr post-exenatide administration to male mice, Kitl and Glp1r mRNA expression levels were significantly increased, and Pdgfa mRNA expression level also showed a tendency toward increase. TM4 cells were treated with various cell-activating agents, and bucladesine elicited significantly increased Glp1r mRNA expression. We suggest that GLP-1 provides acute stimulation of Sertoli cells in the mouse testis and has a stimulatory effect on the expression of spermatogenesis-related genes.
胰高血糖素样肽-1（GLP-1）是一种在进食后从胃肠道中释放的肠促胰岛素，可刺激胰岛β细胞分泌胰岛素。最近有报道称，肠促胰岛素具有胰外作用，预计它们对男性不育症和糖尿病等疾病具有潜在疗效。然而，肠促胰岛素对男性生殖功能的影响尚不清楚。在这项研究中，使用小鼠睾丸和睾丸衍生的培养细胞系研究了 GLP-1 受体表达和 GLP-1 对精子发生相关基因的影响。Glp1r mRNA 和 GLP-1 在小鼠睾丸中的表达水平与阳性对照脂肪组织、肝脏和肠道相当或更高，并且在 Sertoli 细胞系（TM4）和 Leydig 细胞系（MA-10）以及 GC-1 spg 和 GC-2 spd（ts）生殖细胞系中也有表达。用 GLP-1 受体激动剂 exenatide 处理的 TM4 细胞显示 Kitl、Pdgfa 和 Glp1r mRNA 表达瞬时且显著上调。此外，在给予雄性小鼠 exenatide 后 1 小时，Kitl 和 Glp1r mRNA 表达水平显著增加，Pdgfa mRNA 表达水平也表现出增加的趋势。用各种细胞激活剂处理 TM4 细胞，布他色林引起 Glp1r mRNA 表达显著增加。我们认为 GLP-1 对小鼠睾丸中的 Sertoli 细胞提供急性刺激，并对精子发生相关基因的表达具有刺激作用。
