Expression of IL‐33 in rodent testes and its role in Leydig cell steroidogenesis and aging

作者：Hu Wang, Yun Hu, Zhenni Li, Enhui Wu, Qichao Yuan, Xinyu Niu, Jingwen Liu, Hanmin Cai, Mengjie Qin, Jingfeng Xu, Jiexia Wang, Xiaoju Guan, Haolin Chen, Congde Chen · 发表于：Andrology · 年份：2025 · DOI：10.1111/andr.70078 · 被引用次数：4 · 研究领域：IL-33, ST2, and ILC Pathways、Dermatology and Skin Diseases、Reproductive System and Pregnancy

BACKGROUND: Serum testosterone (T) concentration declines with aging in men, potentially affecting reproduction, mental and physical well-beings. A role of immune factors in Leydig cell (LC) function is well-known, but the specific factors involved, especially these playing roles in LC aging, are still unclear. This study investigated effects of interleukin 33 (IL-33) on LC function and its expression during testicular aging. METHODS: Immunohistochemistry and Western blotting were used to determine IL-33 and its receptor IL1RL1 expressions in testes of young (3-month-old) and old (19-24-month-old) Wistar rats. In vitro, the effects of IL-33 on sex steroid hormone productions were evaluated in primary and MLTC-1 LCs over 2-24 h. Different steroidogenic stimulators or signaling molecules (luteinizing hormone [LH], 8-Br-cAMP, Forskolin, pertussis toxin, and MAPK activators) were compared with elucidate mechanisms. Steroidogenic pathway proteins and potential signaling molecules were explored by Western blotting. RESULTS: IL-33 is expressed by mesenchymal cells, with the number increasing significantly with aging. IL1RL1, its receptor, is expressed by LCs and remains unchanged. In vitro, IL-33 acutely inhibited LC steroidogenesis in a dose-dependent manner (1-100 ng/mL) within 2-24 h. The effect was LH-dependent; replacing LH with either 8-Br-cAMP or Forskolin abolished the inhibition. IL-33 mainly affected STAR in the steroidogenic pathway. Signaling molecules involving STAR reg...