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.

Weight gain and inflammation regulate aromatase expression in male adipose tissue, as evidenced by reporter gene activity

“…The tissue distribution of Luc reporter in hARO-Luc mice closely resembles that described for CYP19A1 gene in human tissues (Strauss et al, 2013). The objective of this study was to investigate the regulation of human CYP19A1 gene in different WAT depots in obese male hARO-Luc mice, and to identify exogenous factors that can modulate CYP19A1 expression in WAT of obese individuals.…”

“…In order to study the expression pattern and regulation of human CYP19A1 gene in vivo, we have generated a transgenic reporter mouse model (hARO-Luc mouse) with >100-kb 5′-region of human CYP19A1 gene attached to a luciferase (Luc) reporter gene (Strauss et al, 2013). The tissue distribution of Luc reporter in hARO-Luc mice closely resembles that described for CYP19A1 gene in human tissues (Strauss et al, 2013).…”

“…Luc activity was analyzed as previously described (Strauss et al, 2013). All reagents were obtained from Life Technologies (Life Technologies Ltd, Carlsbad, CA), unless stated otherwise.…”

Is testosterone important in LUT function in men and women? ICI‐RS 2015

“…In addition, steroidogenic pathway enzymes have a wide expression, such as the CYP19A1/aromatase gene which is expressed in both gonadal and several extra‐gonadal tissues, including the ovaries, testis, placenta, bone, brain, adipose tissue, blood vessels, skin, and fetal liver. Interestingly, a high level of CYP19A1 expression has been reported in urinary bladder tissue in male humans and mice . Much of the research into LUT sex hormone signaling has focused on benign prostate hyperplasia (BPH) and prostate and bladder cancer.…”

“…Interestingly, a high level of CYP19A1 expression has been reported in urinary bladder tissue in male humans and mice. 10 Much of the research into LUT sex hormone signaling has focused on benign prostate hyperplasia (BPH) 1 and prostate and bladder cancer. However, little is known about the physiological role of these hormones especially T signaling, in normal LUT function, notably the bladder and urethra and its role in lower urinary tract symptoms (LUTS).…”