Differential effects of exogenous androgen and an androgen receptor antagonist in the peri- and postpubertal murine mammary gland

Peters, A. A., Ingman, W. V., Tilley, W. D. and Butler, L. M. (2011) Differential effects of exogenous androgen and an androgen receptor antagonist in the peri- and postpubertal murine mammary gland. Endocrinology, 152 10: 3728-3737. doi:10.1210/en.2011-1133


Author Peters, A. A.
Ingman, W. V.
Tilley, W. D.
Butler, L. M.
Title Differential effects of exogenous androgen and an androgen receptor antagonist in the peri- and postpubertal murine mammary gland
Journal name Endocrinology   Check publisher's open access policy
ISSN 0013-7227
1945-7170
Publication date 2011-10
Sub-type Article (original research)
DOI 10.1210/en.2011-1133
Volume 152
Issue 10
Start page 3728
End page 3737
Total pages 10
Place of publication Chevy Chase, MD, U.S.A.
Publisher The Endocrine Society
Collection year 2012
Language eng
Formatted abstract
There is emerging evidence that androgens inhibit proliferation of normal and malignant breast epithelial cells, but the actions of androgens in normal mammary gland morphogenesis are not well understood. In this study, we investigated whether development of the murine mammary gland could be altered by stimulating or suppressing androgen receptor (AR) signaling in vivo. Intact virgin female mice aged 5 wk (midpuberty) or 12 wk (postpuberty) were implanted with slow-release pellets containing either placebo, 5α-dihydrotestosterone (1.5 mg) or the AR antagonist flutamide (60 mg). Treatment with 5α-dihydrotestosterone from midpuberty to 12 wk of age-retarded ductal extension by 40% (P = 0.007), but treatment from 12–21 wk had no significant effect on gland morphology. In contrast, inhibition of AR signaling with flutamide from midpuberty had no effect on the mammary gland, but flutamide treatment from 12–21 wk increased ductal branching (P = 0.004) and proliferation (P = 0.03) of breast epithelial cells. The increased proliferation in flutamide-treated mice was not correlated with serum estradiol levels or estrogen receptor-α (ERα) expression. In control mice, the frequency and intensity of AR immunostaining in mammary epithelial cells was significantly increased in the 12- to 21-wk treatment group compared with the 5- to 12-wk group (P < 0.001). In contrast, no change in ERα occurred, resulting in a marked increase in the AR to ERα ratio from 0.56 (±0.12) to 1.47 (±0.10). Our findings indicate that androgen signaling influences development and structure of the adult mammary gland and that homeostasis between estrogen and androgen signaling in mature glands is critical to constrain the proliferative effects of estradiol.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Pharmacy Publications
 
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Created: Tue, 23 Aug 2011, 09:26:48 EST by Dr Amelia Peters on behalf of School of Pharmacy