Expression profiling of key androgen-metabolizing enzymes in canine sebaceous gland tumors.

Abstract

This study investigated the expression profiles of key enzymes involved in androgen metabolism in canine sebaceous gland tumors and compared them with those in normal and hyperplastic sebaceous glands. Based on histopathological evaluation, lesions were classified as hyperplasia, adenoma, epithelioma, or carcinoma. Tissue sections from each case were examined for expression of the androgen receptor (AR); the de novo steroidogenic enzymes StAR, CYP11A1, CYP17A1, and 3β-HSD; the steroid-precursor-activating enzyme STS; the potent-androgen biosynthetic enzymes 17β-HSD3 and SRD5A1; the androgen-inactivating enzyme 17β-HSD2; and the aromatase CYP19A1, using immunohistochemistry and in situ hybridization to assess both protein and mRNA levels. Normal sebaceous glands exhibited immunoreactivity for all examined enzymes and AR except 17β-HSD3, and no significant differences were observed between normal and hyperplastic glands. In contrast, malignant sebaceous gland tumors showed marked up-regulation of AR, StAR, CYP11A1, CYP17A1, 3β-HSD, and SRD5A1, accompanied by down-regulation of 17β-HSD2 and CYP19A1 relative to both normal and hyperplastic counterparts. Collectively, these findings demonstrate that normal sebaceous glands possess an intrinsic ability for local sex-steroid biosynthesis, suggesting a role for these hormones in the physiological regulation of sebaceous gland function. Moreover, the enzyme-expression alterations observed in sebaceous gland tumors suggest a shift in the local hormonal milieu toward an increased androgenic influence. Overall, the results underscore the pivotal role of steroid metabolism in the pathogenesis of sebaceous gland tumors and suggest that androgen-biosynthetic pathways may offer promising therapeutic targets.