Impact of sex, androgens, and prostate size on C57BL/6J mouse urinary physiology: functional assessment
Year: 2019
Type: article
Abstract: ABSTRACT Laboratory mice are used to identify causes of urinary dysfunction including prostate-related mechanisms of Lower Urinary Tract Symptoms (LUTS). Effective use of mice for this purpose requires a clear understanding of molecular, cellular, anatomical, and endocrine contributions to voiding function. Whether the prostate influences baseline voiding function has not been specifically evaluated, in part because most methods that alter prostate mass also change circulating testosterone concentrations. We performed void spot assay and cystometry to establish a multi-parameter “baseline” of voiding function in intact male and female 9-week-old (adult) C57BL/6J mice. We then compared voiding function in intact male mice to that of castrate males, males (and females) treated with the steroid five alpha reductase inhibitor finasteride, or males harboring alleles ( Pbsn4 cre/+ ; R26R Dta/+ ) that significantly reduce prostate lobe mass by depleting prostatic luminal epithelial cells. We evaluated aging-related changes in male urinary voiding. We also treated intact male, castrate male, and female mice with exogenous testosterone to determine the influence of androgen on voiding function. The three methods used to reduce prostate mass (castration, finasteride, Pbsn4 cre/+ ; R26R Dta/+ ) changed voiding function from baseline but in a nonuniform manner. Castration feminized some aspects of male urinary physiology (making them more like intact female) while exogenous testosterone masculinized some aspects of female urinary physiology (making them more like intact male). Our results provide evidence that circulating testosterone is responsible in part for baseline sex differences in C57BL/6J mouse voiding function while prostate lobe mass in young, healthy adult mice has a lesser influence.
Language: English
Subfield: Urology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: University of Wisconsin-Madison, National Institutes of Health, Institute for Clinical and Translational Research, University of Wisconsin, Madison, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Institute of Environmental Health Sciences, National Center for Advancing Translational Sciences
Awards: G2143765376, G3517362731, G4639854416, G6522717018, Role of DNA methylation in prostate glandular development and urinary function, G8442414799, TCDD Reprograms Prostate Stroma and Causes Fibrosis to Induce Urinary Dysfunction, G9000190088, G9000272971, G9000354210, Cancer Center Support Grant, NRSA Training Core, Reproductive and Developmental Toxicity of Dioxin
OpenAlex ID: W2964384112