title: 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.
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 ∼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.
authors.affiliation: Department of Physiology, University of Turku, Turku, Finland.
authors.forename: Leena
authors.initials: L
authors.lastname: Strauss
authors.forename: Pia
authors.initials: P
authors.lastname: Rantakari
authors.forename: Klara
authors.initials: K
authors.lastname: Sjögren
authors.forename: Anu
authors.initials: A
authors.lastname: Salminen
authors.forename: Eve
authors.initials: E
authors.lastname: Lauren
authors.forename: Jenny
authors.initials: J
authors.lastname: Kallio
authors.forename: Pauliina
authors.initials: P
authors.lastname: Damdimopoulou
authors.forename: Minna
authors.initials: M
authors.lastname: Boström
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Boström
authors.forename: Pirjo
authors.initials: P
authors.lastname: Pakarinen
authors.forename: FuPing
authors.initials: F
authors.lastname: Zhang
authors.forename: Paula
authors.initials: P
authors.lastname: Kujala
authors.forename: Claes
authors.initials: C
authors.lastname: Ohlsson
authors.forename: Sari
authors.initials: S
authors.lastname: Mäkelä
authors.forename: Matti
authors.initials: M
authors.lastname: Poutanen
mesh_terms: D000728:Androgens / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D011401:Promoter Regions, Genetic / Q000235:genetics; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012669:Seminal Vesicles / Q000378:metabolism*; D013737:Testis / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism*
chemical_list: D000728:Androgens; D008156:Luciferases; D001141:Aromatase; C561410:CYP19A1 protein, human