Differential Expression of LHR and FSHR in Canine Mammary Tumors: Correlation with Malignancy and Spay Status

Canine mammary tumors (CMTs) constitute one of the most prevalent malignancies in female canines, whereas the functional involvement of gonadotropin receptors-luteinizing hormone receptor (LHR) and follicle-stimulating hormone receptor (FSHR)-in these neoplasms remains uncharacterized. This study investigated LHR and FSHR expression in 79 CMTs and 14 normal mammary tissues collected from 59 female dogs (ethical approval AW82903202-2-3), using immunohistochemistry (IHC) and quantitative real-time PCR, specifically examining their association with tumor malignancy and spay status. Relative to normal mammary tissue, CMTs exhibited statistically significant downregulation of both LHR and FSHR transcripts and corresponding proteins (<i>p</i> < 0.01), with expression progressively decreasing as tumor malignancy increased, and with grade 3 tumors showing almost undetectable levels. Notably, spayed dogs displayed higher LHR levels in tumors (<i>p</i> < 0.05), whereas intact dogs showed higher FSHR levels than spayed dogs. These findings suggest that the expression of LHR and FSHR in CMTs may correlate with tumor malignancy and be influenced by the spay status. Our findings provide the first evidence of gonadotropin receptor dysregulation in CMTs, offering novel insights into their molecular mechanisms and potential applications in hormone-related diagnostic or therapeutic strategies.