A1 Refereed original research article in a scientific journal
Seminal vesicles and urinary bladder as sites of aromatization of androgens in men, evidenced by a CYP19A1-driven luciferase reporter mouse and human tissue specimens
Authors: Strauss L, Rantakari P, Sjogren K, Salminen A, Lauren E, Kallio J, Damdimopoulou P, Bostrom M, Bostrom PJ, Pakarinen P, Zhang FP, Kujala P, Ohlsson C, Makela S, Poutanen M
Publisher: FEDERATION AMER SOC EXP BIOL
Publication year: 2013
Journal: FASEB Journal
Journal name in source: FASEB JOURNAL
Journal acronym: FASEB J
Number in series: 4
Volume: 27
Issue: 4
First page : 1342
Last page: 1350
Number of pages: 9
ISSN: 0892-6638
DOI: https://doi.org/10.1096/fj.12-219048
Abstract
The human CYP19A1 gene is expressed in various tissues by the use of tissue-specific promoters, whereas the rodent cyp19a1 gene is expressed mainly in the gonads and brain. We generated a transgenic mouse model containing a > 100-kb 5' region of human CYP19A1 gene connected to a luciferase reporter gene. The luciferase activity in mouse tissues mimicked the CYP19A1 gene expression pattern in humans. Interestingly, the reporter gene activity was 16 and 160 times higher in the urinary bladder and seminal vesicles, respectively, as compared with the activity in the testis. Accordingly, CYP19A1 gene and P450arom protein expression was detected in those human tissues. Moreover, the data revealed that the expression of CYP19A1 gene is driven by promoters PII, I. 4, and I. 3 in the seminal vesicles, and by promoters PII and I. 4 in the urinary bladder. Furthermore, the reporter gene expression in the seminal vesicles was androgen dependent: Castration decreased the expression similar to 20 times, and testosterone treatment restored it to the level of an intact mouse. This reporter mouse model facilitates studies of tissue-specific regulation of the human CYP19A1 gene, and our data provide evidence for seminal vesicles as important sites for estrogen production in males.-Strauss, L., Rantakari, P., Sjogren, K., Salminen, A., Lauren, E., Kallio, J., Damdimopoulou, P., Bostrom, M., Bostrom, P. J., Pakarinen, P., Zhang, F. P., Kujala, P., Ohlsson, C., Makela, S., Poutanen, M. Seminal vesicles and urinary bladder as sites of aromatization of androgens in men, evidenced by a CYP19A1-driven luciferase reporter mouse and human tissue specimens. FASEB J. 27, 1342-1350 (2013). www.fasebj.org
The human CYP19A1 gene is expressed in various tissues by the use of tissue-specific promoters, whereas the rodent cyp19a1 gene is expressed mainly in the gonads and brain. We generated a transgenic mouse model containing a > 100-kb 5' region of human CYP19A1 gene connected to a luciferase reporter gene. The luciferase activity in mouse tissues mimicked the CYP19A1 gene expression pattern in humans. Interestingly, the reporter gene activity was 16 and 160 times higher in the urinary bladder and seminal vesicles, respectively, as compared with the activity in the testis. Accordingly, CYP19A1 gene and P450arom protein expression was detected in those human tissues. Moreover, the data revealed that the expression of CYP19A1 gene is driven by promoters PII, I. 4, and I. 3 in the seminal vesicles, and by promoters PII and I. 4 in the urinary bladder. Furthermore, the reporter gene expression in the seminal vesicles was androgen dependent: Castration decreased the expression similar to 20 times, and testosterone treatment restored it to the level of an intact mouse. This reporter mouse model facilitates studies of tissue-specific regulation of the human CYP19A1 gene, and our data provide evidence for seminal vesicles as important sites for estrogen production in males.-Strauss, L., Rantakari, P., Sjogren, K., Salminen, A., Lauren, E., Kallio, J., Damdimopoulou, P., Bostrom, M., Bostrom, P. J., Pakarinen, P., Zhang, F. P., Kujala, P., Ohlsson, C., Makela, S., Poutanen, M. Seminal vesicles and urinary bladder as sites of aromatization of androgens in men, evidenced by a CYP19A1-driven luciferase reporter mouse and human tissue specimens. FASEB J. 27, 1342-1350 (2013). www.fasebj.org
UTU Research Portal