Abundance of estrogen receptors involved in non-canonical signaling in the dog testis

Abstract

With estrogen regulation of the reproductive system, G-protein-coupled membrane estrogen receptor (GPER) and estrogen-related receptors (ERRs) are implicated. Non-canonical receptors can bind estrogens such as environmental and pharmacological chemicals. These compounds induce rapid non-genomic pathways or receptor interaction including autoactivation. Testicular tumors occur in dogs more frequently than in other domestic animals. Also, in recent decades there were increased occurrences of various tumor types in dogs. Using qRT-PCR, Western blot and immunohistochemistry procedures in the present study, there was determination of abundance pattern of GPER, ERRα, β and γ in dog tests when there were intratubular germ cell tumors. There was quantitation of estradiol, cyclic GMP and calcium ions (Ca2⁺). There were changes (P < 0.01; P < 0.001) in GPER, ERRα and β in both mRNA transcript and protein abundances including less (P < 0.001) co-abundance of ERRγ mRNA transcript and protein. Receptors were mainly located in Leydig cells with there being receptor delocalization to the cell cytoplasm or occasionally detections in the seminiferous tubule epithelia, especially of testicular tumor tissues. There were also greater estradiol (P < 0.05) and lesser cGMP and Ca2⁺ concentrations in testicular tumor tissues indicating there was a disrupted sex steroid milieu and tumor cell metastasis. Results from the present study provide further evidence that ERRγ has marked actions in testicular germ cell tumor initiation and development and in further structural-functional disruptions of dog testis. Concomitantly, abundance pattern of GPER and ERRs, relative to concentrations of cGMP and Ca2⁺, may be an additional indicator of intratubular germ cell tumors in dogs.

Keywords: Dog; Estrogen-related receptor; G-protein-coupled estrogen receptor; Testis; Tumor.