Potential role of insulin-like growth factor 1 and growth hormone in acneiform eruptions: evidence from a rat model of acromegaly.

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.