College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, 210095, China.
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei Province, 430070, China; Department of Surgery, Anesthesiology, and Radiology, Faculty of Veterinary Medicine, Benha University, Moshtohor, 13736, Egypt.
Theriogenology. 2024 Dec;230:130-141. doi: 10.1016/j.theriogenology.2024.09.010. Epub 2024 Sep 14.
Testosterone is secreted by Leydig cells (LCs), which play an important physiological role in preserving male secondary sex characteristics, protecting male reproductive function, and establishing the blood-testis barrier. Studies have shown that autophagy is particularly active in LCs; however, its involvement in testosterone synthesis in porcine LCs has not been fully explored. Therefore, this experiment aimed to investigate the influence of autophagy on testosterone secretion in porcine LCs and its potential regulatory mechanism. Our results demonstrated that both testicular autophagy and serum testosterone levels increased in piglets during postnatal development from 4 to 18 weeks. In addition, autophagy was found to degrade the Na/H exchange regulatory factor 2 (NHERF2), leading to the up-regulation of scavenger receptor class B type 1 (SRB1). This process resulted in increased cholesterol intake and enhanced testosterone production. The observable level of sirtuin 1 (SIRT1) was directly proportional to the level of autophagy. In vitro investigations have shown that SIRT1 can affect the level of autophagy, cholesterol uptake as well as testosterone release. In conclusion, testosterone synthesis during pig development is regulated by SIRT1. SIRT1 mediates the degradation of NHERF2 through autophagy, thereby weakening its negative regulatory effect on the high-density lipoprotein receptor SRB1 in Leydig cells. This process increases cholesterol uptake and enhances testosterone synthesis.
睾酮由莱迪希细胞（LCs）分泌，在维持男性第二性征、保护男性生殖功能和建立血睾屏障方面发挥着重要的生理作用。研究表明，自噬在 LCs 中特别活跃；然而，其在猪 LCs 中对睾酮合成的参与尚未得到充分探索。因此，本实验旨在研究自噬对猪 LCs 中睾酮分泌的影响及其潜在的调节机制。我们的结果表明，在从 4 周到 18 周的仔猪出生后发育过程中，睾丸自噬和血清睾酮水平都增加了。此外，自噬被发现可降解钠/氢交换调节因子 2（NHERF2），从而上调清道夫受体 B 类 1（SRB1）。这一过程导致胆固醇摄取增加，进而促进睾酮生成。Sirtuin 1（SIRT1）的可观察水平与自噬水平直接相关。体外研究表明，SIRT1 可以影响自噬水平、胆固醇摄取以及睾酮释放。综上所述，猪发育过程中的睾酮合成受 SIRT1 调节。SIRT1 通过自噬介导 NHERF2 的降解，从而削弱其对 Leydig 细胞中高密度脂蛋白受体 SRB1 的负调控作用。这一过程增加了胆固醇摄取并增强了睾酮合成。
