Mengjie Fan, Yangfan Lai, Xiaoyao Fan, Yichang Yuan, Jin Chen, Yanzhuo Hu, Ye Liu, Min He, Meiyan Liu, Hongying Ye, Zhaoyun Zhang, Yongfei Wang, Leihong Xiang, Zhengyuan Chen, Ying Ma
{"title":"Potential role of insulin-like growth factor 1 and growth hormone in acneiform eruptions: evidence from a rat model of acromegaly.","authors":"Mengjie Fan, Yangfan Lai, Xiaoyao Fan, Yichang Yuan, Jin Chen, Yanzhuo Hu, Ye Liu, Min He, Meiyan Liu, Hongying Ye, Zhaoyun Zhang, Yongfei Wang, Leihong Xiang, Zhengyuan Chen, Ying Ma","doi":"10.1007/s40618-025-02692-4","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Acne, a chronic inflammatory disease, is influenced by insulin-like growth factor 1 (IGF-1). Acromegaly, characterized by excessive growth hormone (GH) and IGF-1, is associated with a higher prevalence of acne, though the underlying mechanisms remain unclear.</p><p><strong>Objective: </strong>This study aims to explore the underlying mechanisms why patients with acromegaly are more susceptible to acne, especially refractory acne.</p><p><strong>Methods: </strong>An acromegaly rat model was established via biweekly long-acting recombinant human GH (rhGH) injections for eight weeks. Serum levels of GH, IGF-1, and glucose were measured, and skin pathology was examined. Immunohistochemistry, transcriptomics, and proteomics were performed to explore molecular pathways, with RT-qPCR and western blot validation.</p><p><strong>Results: </strong>Serum GH and IGF-1 levels significantly increased from week 3 and remained elevated throughout the study in the rhGH-treated group. Acneiform lesions, including epidermal hyperkeratosis, sebaceous gland hyperplasia, and dermal thickening, were observed. Immunohistochemical analysis revealed upregulation of IGF-1, IGF-1R, SREBP1, and IL-1β. Transcriptomic and proteomic analyses identified 1,112 differentially expressed genes and 440 differentially expressed proteins, underscoring the activation of inflammation, extracellular matrix (ECM) remodeling, epithelial-mesenchymal transition (EMT), and cell proliferation through PI3K/Akt pathways. Significant upregulation of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase 1 (TIMP-1) was observed in both transcriptomic and proteomic analyses.</p><p><strong>Conclusion: </strong>Chronic GH stimulation leads to persistent IGF-1 elevation, promoting acne by increasing IGF-1R expression and disrupting ECM remodeling via PI3K/Akt-regulated MMPs and TIMP-1. These findings help clarify the link between acromegaly and acne and provide mechanistic insights into the role of IGF-1 in acne pathogenesis.</p>","PeriodicalId":48802,"journal":{"name":"Journal of Endocrinological Investigation","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Endocrinological Investigation","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s40618-025-02692-4","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Acne, a chronic inflammatory disease, is influenced by insulin-like growth factor 1 (IGF-1). Acromegaly, characterized by excessive growth hormone (GH) and IGF-1, is associated with a higher prevalence of acne, though the underlying mechanisms remain unclear.
Objective: This study aims to explore the underlying mechanisms why patients with acromegaly are more susceptible to acne, especially refractory acne.
Methods: An acromegaly rat model was established via biweekly long-acting recombinant human GH (rhGH) injections for eight weeks. Serum levels of GH, IGF-1, and glucose were measured, and skin pathology was examined. Immunohistochemistry, transcriptomics, and proteomics were performed to explore molecular pathways, with RT-qPCR and western blot validation.
Results: Serum GH and IGF-1 levels significantly increased from week 3 and remained elevated throughout the study in the rhGH-treated group. Acneiform lesions, including epidermal hyperkeratosis, sebaceous gland hyperplasia, and dermal thickening, were observed. Immunohistochemical analysis revealed upregulation of IGF-1, IGF-1R, SREBP1, and IL-1β. Transcriptomic and proteomic analyses identified 1,112 differentially expressed genes and 440 differentially expressed proteins, underscoring the activation of inflammation, extracellular matrix (ECM) remodeling, epithelial-mesenchymal transition (EMT), and cell proliferation through PI3K/Akt pathways. Significant upregulation of matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinase 1 (TIMP-1) was observed in both transcriptomic and proteomic analyses.
Conclusion: Chronic GH stimulation leads to persistent IGF-1 elevation, promoting acne by increasing IGF-1R expression and disrupting ECM remodeling via PI3K/Akt-regulated MMPs and TIMP-1. These findings help clarify the link between acromegaly and acne and provide mechanistic insights into the role of IGF-1 in acne pathogenesis.
期刊介绍:
The Journal of Endocrinological Investigation is a well-established, e-only endocrine journal founded 36 years ago in 1978. It is the official journal of the Italian Society of Endocrinology (SIE), established in 1964. Other Italian societies in the endocrinology and metabolism field are affiliated to the journal: Italian Society of Andrology and Sexual Medicine, Italian Society of Obesity, Italian Society of Pediatric Endocrinology and Diabetology, Clinical Endocrinologists’ Association, Thyroid Association, Endocrine Surgical Units Association, Italian Society of Pharmacology.