{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T18:46:37Z","timestamp":1784054797480,"version":"3.55.0"},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Serum testosterone (T) concentration declines with aging in men, potentially affecting reproduction, mental and physical well\u2010beings. A role of immune factors in Leydig cell (LC) function is well\u2010known, but the specific factors involved, especially these playing roles in LC aging, are still unclear. This study investigated effects of interleukin 33 (IL\u201033) on LC function and its expression during testicular aging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Immunohistochemistry and Western blotting were used to determine IL\u201033 and its receptor IL1RL1 expressions in testes of young (3\u2010month\u2010old) and old (19\u201324\u2010month\u2010old) Wistar rats. In vitro, the effects of IL\u201033 on sex steroid hormone productions were evaluated in primary and MLTC\u20101 LCs over 2\u201324\u00a0h. Different steroidogenic stimulators or signaling molecules (luteinizing hormone [LH], 8\u2010Br\u2010cAMP, Forskolin, pertussis toxin, and MAPK activators) were compared with elucidate mechanisms. Steroidogenic pathway proteins and potential signaling molecules were explored by Western blotting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>IL\u201033 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\u201033 acutely inhibited LC steroidogenesis in a dose\u2010dependent manner (1\u2013100\u00a0ng\/mL) within 2\u201324\u00a0h. The effect was LH\u2010dependent; replacing LH with either 8\u2010Br\u2010cAMP or Forskolin abolished the inhibition. IL\u201033 mainly affected STAR in the steroidogenic pathway. Signaling molecules involving STAR regulation (AKT and MAPK) were down\u2010regulated while PKA phosphorylation was increased. P38 MAPK involvement was confirmed as increased Tyr182 phosphorylation of P38 by SB203580 partly reversed the IL\u201033\u2010induced steroidogenesis inhibition.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Testicular mesenchymal cells can synthesize IL\u201033, and LCs express the receptor IL1RL1. IL\u201033 inhibits LC steroidogenesis in vitro, partially via inhibiting P38 MAPK phosphorylation. As IL\u201033\u2010expressing cell numbers rise significantly with aging, its role in age\u2010related LC T production decline warrants further study.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70078","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T08:23:18Z","timestamp":1750062198000},"page":"247-261","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Expression of IL\u201033 in rodent testes and its role in Leydig cell steroidogenesis and aging"],"prefix":"10.1111","volume":"14","author":[{"given":"Hu","family":"Wang","sequence":"first","affiliation":[{"name":"Key Laboratory of Children Genitourinary Diseases of Wenzhou City, Key Laboratory of Structural Malformations in Children of Zhejiang Province, Department of Pediatric Urology the Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University  Wenzhou Zhejiang 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