Overexpression of aromatase leads to development of testicular Leydig cell tumors: An in vivo model for hormone-mediated testicular cancer

Keith A. Fowler, Kiran Gill, Nameer Kirma, Dirck L. Dillehay, Rajeshwar Rao Tekmal

Research output: Contribution to journalArticlepeer-review

105 Scopus citations


Despite recent advances in diagnosis and treatment of testicular cancer, its causes remain unknown. The most common conditions known to be associated with testicular cancer are cryptorchidism, infertility, and overexposure to pesticides or radiation. Recent studies also indicate hormones may play a crucial role in testicular tumorigenesis. Our studies show that about half of the male transgenic mice overexpressing aromatase in testis were infertile and/or had larger than normal testicles. Gross pathology and histological analysis showed the mice to have Leydig cell tumors, unilaterally or bilaterally. Serum estradiol levels for transgenic mice were at least twice as high as those for nontransgenic mice. Expression of aromatase and estrogen receptor were also very high in testicular tissue of transgenic mice compared to non-transgenic mice. Consistent with increased estrogenic activity in the testicular tissue, we also saw an increase in the levels of genes involved in cell cycle that are regulated by the estrogen. To obtain a better understanding of the biological significance of testicular tumorigenesis, a reliable animal model is necessary to clarify the mechanisms and correlations associated with human cancers. Here we describe such a model, which shows that overexpression of aromatase results in increased estrogen production and a changed hormone milieu, leading to the induction of testicular cancer (Leydig cell tumors). This predictable and useful model is a potential tool for the study of testicular tumorigenesis, hormonal carcinogenesis, synergistic action of other carcinogens on hormone-induced tumors, and tumor dependency on endocrine factors.

Original languageEnglish (US)
Pages (from-to)347-353
Number of pages7
JournalAmerican Journal of Pathology
Issue number1
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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