Tags

Type your tag names separated by a space and hit enter

Targeting stromal androgen receptor suppresses prolactin-driven benign prostatic hyperplasia (BPH).
Mol Endocrinol 2013; 27(10):1617-31ME

Abstract

Stromal-epithelial interaction plays a pivotal role to mediate the normal prostate growth, the pathogenesis of benign prostatic hyperplasia (BPH), and prostate cancer development. Until now, the stromal androgen receptor (AR) functions in the BPH development, and the underlying mechanisms remain largely unknown. Here we used a genetic knockout approach to ablate stromal fibromuscular (fibroblasts and smooth muscle cells) AR in a probasin promoter-driven prolactin transgenic mouse model (Pb-PRL tg mice) that could spontaneously develop prostate hyperplasia to partially mimic human BPH development. We found Pb-PRL tg mice lacking stromal fibromuscular AR developed smaller prostates, with more marked changes in the dorsolateral prostate lobes with less proliferation index. Mechanistically, prolactin mediated hyperplastic prostate growth involved epithelial-stromal interaction through epithelial prolactin/prolactin receptor signals to regulate granulocyte macrophage-colony stimulating factor expression to facilitate stromal cell growth via sustaining signal transducer and activator of transcription-3 activity. Importantly, the stromal fibromuscular AR could modulate such epithelial-stromal interacting signals. Targeting stromal fibromuscular AR with the AR degradation enhancer, ASC-J9(®), led to the reduction of prostate size, which could be used in future therapy.

Authors+Show Affiliations

George Whipple Distinguished University of Rochester Medical Center, 601 Elmwood Avenue, Box 626, Rochester, New York 14642. chang@urmc.rochester.edu.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23893956

Citation

Lai, Kuo-Pao, et al. "Targeting Stromal Androgen Receptor Suppresses Prolactin-driven Benign Prostatic Hyperplasia (BPH)." Molecular Endocrinology (Baltimore, Md.), vol. 27, no. 10, 2013, pp. 1617-31.
Lai KP, Huang CK, Fang LY, et al. Targeting stromal androgen receptor suppresses prolactin-driven benign prostatic hyperplasia (BPH). Mol Endocrinol. 2013;27(10):1617-31.
Lai, K. P., Huang, C. K., Fang, L. Y., Izumi, K., Lo, C. W., Wood, R., ... Chang, C. (2013). Targeting stromal androgen receptor suppresses prolactin-driven benign prostatic hyperplasia (BPH). Molecular Endocrinology (Baltimore, Md.), 27(10), pp. 1617-31. doi:10.1210/me.2013-1207.
Lai KP, et al. Targeting Stromal Androgen Receptor Suppresses Prolactin-driven Benign Prostatic Hyperplasia (BPH). Mol Endocrinol. 2013;27(10):1617-31. PubMed PMID: 23893956.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Targeting stromal androgen receptor suppresses prolactin-driven benign prostatic hyperplasia (BPH). AU - Lai,Kuo-Pao, AU - Huang,Chiung-Kuei, AU - Fang,Lei-Ya, AU - Izumi,Kouji, AU - Lo,Chi-Wen, AU - Wood,Ronald, AU - Kindblom,Jon, AU - Yeh,Shuyuan, AU - Chang,Chawnshang, Y1 - 2013/07/26/ PY - 2013/7/30/entrez PY - 2013/7/31/pubmed PY - 2014/4/26/medline SP - 1617 EP - 31 JF - Molecular endocrinology (Baltimore, Md.) JO - Mol. Endocrinol. VL - 27 IS - 10 N2 - Stromal-epithelial interaction plays a pivotal role to mediate the normal prostate growth, the pathogenesis of benign prostatic hyperplasia (BPH), and prostate cancer development. Until now, the stromal androgen receptor (AR) functions in the BPH development, and the underlying mechanisms remain largely unknown. Here we used a genetic knockout approach to ablate stromal fibromuscular (fibroblasts and smooth muscle cells) AR in a probasin promoter-driven prolactin transgenic mouse model (Pb-PRL tg mice) that could spontaneously develop prostate hyperplasia to partially mimic human BPH development. We found Pb-PRL tg mice lacking stromal fibromuscular AR developed smaller prostates, with more marked changes in the dorsolateral prostate lobes with less proliferation index. Mechanistically, prolactin mediated hyperplastic prostate growth involved epithelial-stromal interaction through epithelial prolactin/prolactin receptor signals to regulate granulocyte macrophage-colony stimulating factor expression to facilitate stromal cell growth via sustaining signal transducer and activator of transcription-3 activity. Importantly, the stromal fibromuscular AR could modulate such epithelial-stromal interacting signals. Targeting stromal fibromuscular AR with the AR degradation enhancer, ASC-J9(®), led to the reduction of prostate size, which could be used in future therapy. SN - 1944-9917 UR - https://www.unboundmedicine.com/medline/citation/23893956/Targeting_stromal_androgen_receptor_suppresses_prolactin_driven_benign_prostatic_hyperplasia__BPH__ L2 - https://academic.oup.com/mend/article-lookup/doi/10.1210/me.2013-1207 DB - PRIME DP - Unbound Medicine ER -