Testosterone and 17β-estradiol induce glandular prostatic growth, bladder outlet obstruction, and voiding dysfunction in male mice

Tristan M. Nicholson, Emily A. Ricke, Paul C. Marker, Joseph M. Miano, Robert D. Mayer, Barry G. Timms, Frederick S. Vom Saal, Ronald W. Wood, William A. Ricke

Research output: Contribution to journalArticle

Abstract

Benign prostatic hyperplasia (BPH) and bladder outlet obstruction (BOO) arecommonin oldermen and can contribute to lower urinary tract symptoms that significantly impact quality of life. Few existing models of BOO and BPH use physiological levels of hormones associated with disease progression in humans in a genetically manipulable organism. We present a model of BPH and BOO induced in mice with testosterone (T) and 17β-estradiol (E2). Male mice were surgically implanted with slow-releasing sc pellets containing 25 mg T and 2.5 mg E2 (T+E2). After 2 and 4 months of hormone treatment, we evaluated voiding patterns and examined the gross morphology and histology of the bladder, urethra, and prostate. Mice treated with T+E 2 developed significantly larger bladders than untreated mice, consistent with BOO. Some mice treated with T+E2 had complications in the form of bladder hypertrophy, diverticula, calculi, and eventual decompensation with hydronephrosis. Hormone treatment caused a significant decrease in the size of the urethral lumen, increased prostate mass, and increased number of prostatic ducts associated with the prostatic urethra, compared with untreated mice. Voiding dysfunction was observed in mice treated with T+E2, who exhibited droplet voiding pattern with significantly decreased void mass, shorter void duration, and fewer sustained voids. The constellation of lower urinary tract abnormalities, including BOO, enlarged prostates, and voiding dysfunction seen in male mice treated with T+E 2 is consistent with BPH in men. This model is suitable for better understanding molecular mechanisms and for developing novel strategies to address BPH and BOO.

Original languageEnglish (US)
Pages (from-to)5556-5565
Number of pages10
JournalEndocrinology
Volume153
Issue number11
DOIs
StatePublished - Nov 1 2012
Externally publishedYes

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Urinary Bladder Neck Obstruction
Testosterone
Estradiol
Prostatic Hyperplasia
Growth
Prostate
Hormones
Urethra
Urinary Bladder
Lower Urinary Tract Symptoms
Hydronephrosis
Calculi
Urinary Tract
Hypertrophy
Disease Progression
Histology
Quality of Life

ASJC Scopus subject areas

  • Endocrinology

Cite this

Nicholson, T. M., Ricke, E. A., Marker, P. C., Miano, J. M., Mayer, R. D., Timms, B. G., ... Ricke, W. A. (2012). Testosterone and 17β-estradiol induce glandular prostatic growth, bladder outlet obstruction, and voiding dysfunction in male mice. Endocrinology, 153(11), 5556-5565. https://doi.org/10.1210/en.2012-1522

Testosterone and 17β-estradiol induce glandular prostatic growth, bladder outlet obstruction, and voiding dysfunction in male mice. / Nicholson, Tristan M.; Ricke, Emily A.; Marker, Paul C.; Miano, Joseph M.; Mayer, Robert D.; Timms, Barry G.; Vom Saal, Frederick S.; Wood, Ronald W.; Ricke, William A.

In: Endocrinology, Vol. 153, No. 11, 01.11.2012, p. 5556-5565.

Research output: Contribution to journalArticle

Nicholson, TM, Ricke, EA, Marker, PC, Miano, JM, Mayer, RD, Timms, BG, Vom Saal, FS, Wood, RW & Ricke, WA 2012, 'Testosterone and 17β-estradiol induce glandular prostatic growth, bladder outlet obstruction, and voiding dysfunction in male mice', Endocrinology, vol. 153, no. 11, pp. 5556-5565. https://doi.org/10.1210/en.2012-1522
Nicholson, Tristan M. ; Ricke, Emily A. ; Marker, Paul C. ; Miano, Joseph M. ; Mayer, Robert D. ; Timms, Barry G. ; Vom Saal, Frederick S. ; Wood, Ronald W. ; Ricke, William A. / Testosterone and 17β-estradiol induce glandular prostatic growth, bladder outlet obstruction, and voiding dysfunction in male mice. In: Endocrinology. 2012 ; Vol. 153, No. 11. pp. 5556-5565.
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AU - Mayer, Robert D.

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