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Departments of Physiology (X.L., M.P.) and Anatomy (X.L., A.W., S.M., T.A., T.S., R.S.), Institute of Biomedicine, University of Turku, FIN-20520 Turku, Finland; and Department of Medical Nutrition, Karolinska Institute NOVUM (S.M.), S-14157 Huddinge, Sweden
Address all correspondence and requests for reprints to: Matti Poutanen, Ph.D., Department of Physiology, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland. E-mail: matti.poutanen{at}utu.fi.
We recently generated a transgenic mouse strain that expresses the human aromatase gene under the ubiquitin C promoter (AROM+). We have previously shown that in these mice the serum estradiol concentration is highly elevated, whereas the testosterone concentration is decreased. In the present study we examined mammary gland development in AROM+ male mice at different ages and found that the mammary glands of AROM+ males undergo ductal and alveolar development morphologically resembling that of terminally differentiated female mammary glands, expressing mRNA for a milk protein gene (ß-casein). The male mammary glands also express multiple hormone receptors typical for female mammary gland: estrogen receptor 
and ß, progesterone receptor, and PRL receptor. Furthermore, data showed activation of the Stat5 (signal transducer and activator of transcription 5) signaling pathway in the AROM+ male mammary gland. Interestingly, the phenotype observed is in part reversible. Treatment with finrozole, a specific aromatase inhibitor, caused an involution of the differentiated phenotype of the mammary gland, marked by the disappearance of alveolar structures and the majority of the tertiary side branches of the ducts. The present animal model is a valuable tool for better understanding the cellular and molecular mechanisms involved in the development of gynecomastia.
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