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

## TL;DR

This study finds that hormone receptors LHR and FSHR are less active in aggressive canine mammary tumors, and their levels differ based on whether the dog was spayed.

## Contribution

First evidence of LHR and FSHR dysregulation in canine mammary tumors linked to malignancy and spay status.

## Key findings

- LHR and FSHR are significantly downregulated in canine mammary tumors compared to normal tissue.
- Tumor malignancy correlates with decreasing levels of LHR and FSHR.
- Spayed dogs have higher LHR levels in tumors, while intact dogs have higher FSHR levels.

## Abstract

Canine mammary tumors represent a significant oncological concern in female dogs. Our investigation revealed a marked downregulation of two key reproductive regulators—luteinizing hormone receptor and follicle-stimulating hormone receptor—in canine mammary tumors relative to normal mammary tissues. The most aggressive tumors showed the lowest levels of these receptors. Interestingly, spayed dogs had higher luteinizing hormone receptor levels in their tumors, while intact dogs showed more follicle-stimulating hormone receptor. These findings underscore the crucial roles of both receptors in tumorigenesis and disease progression. By linking receptor levels to tumor behavior and spay status, our research may enable veterinarians to identify high-risk cases earlier and guide novel therapeutic strategies, such as hormone-based therapies, ultimately improving survival rates in dogs with mammary tumors.

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 (p < 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 (p < 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.