Testosterone Modulates Lipid Accumulation and Proliferation of Sebocytes through the Repression of Autophagy

Abstract

Background: Androgen has been regarded as the strongest stimulator of sebum formation and sebocyte proliferation in individuals with acne. However, the underlying mechanisms remain to be elucidated. Recent studies suggest that autophagy is involved in lipid degradation and the regulation of cell proliferation. This study aims to explore the effects of testosterone on autophagy and its potential contribution to lipid accumulation and sebocyte proliferation. Methods: Human SZ95 sebocytes were cultured with linoleic acid (LA) to induce sebum production. This study examined the role of testosterone in acne development by measuring autophagy, lipid accumulation, and cell proliferation. To determine whether testosterones effects on acne depend on autophagy, the autophagy inducer rapamycin and the inhibitor 3-methyladenine (3-MA) were used in combination with LA. Results: The results indicated that treatment with testosterone decreased the levels of LC-3II (p < 0.01) and Beclin 1 (p < 0.01) while increasing p62 level (p < 0.05) in SZ95 cells. Additionally, testosterone treatment induced lipid accumulation, as demonstrated by Oil Red O staining (p < 0.01), and increased Triglyceride (TG) content (p < 0.01) in SZ95 cells. Moreover, testosterone treatment increased cell viability in SZ95 cells according to the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay (p < 0.01) and increased the count of Ki67 positive cells in immunofluorescent staining (p < 0.01). Co-treatment with rapamycin reversed the effects of testosterone on autophagy (p < 0.05 or p < 0.01), lipid accumulation (p < 0.01), and sebocyte proliferation (p < 0.01). In contrast, treatment with 3-MA mimicked all the aforementioned effects of testosterone (p < 0.05 or p < 0.01). Furthermore, immunoblot analysis revealed that treatment with testosterone enhanced the phosphorylation of v-akt murine thymoma viral oncogene homolog (AKT) (p < 0.01) and the mammalian target of rapamycin (mTOR) (p < 0.05), which were counteracted by rapamycin (p < 0.05 or p < 0.01) but mimicked by 3-MA (p < 0.05). Conclusions: These findings suggest that testosterone may facilitate acne progression by activating mTOR and subsequently inhibiting autophagy.