Tissue-Selective Regulation of Androgen-Responsive Genes
- 16 May 2012
- journal article
- research article
- Published by Taylor & Francis Ltd in Endocrine Research
- Vol. 37 (4), 203-215
- https://doi.org/10.3109/07435800.2012.668254
Abstract
Introduction. Androgens regulate a wide array of physiological processes, including male sexual development, bone and muscle growth, and behavior and cognition. Because androgens play a vital role in so many tissues, changes in androgen signaling are associated with a plethora of diseases. How such varied responses are achieved by a single stimulus is not well understood. Androgens act primarily through the androgen receptor (AR), a hormone nuclear receptor that is expressed in a select variety of tissues. Methods. In order to gain a better understanding of how the tissue-selective effects of androgens are achieved, we performed a comparison of microarray data, using previously published datasets and several of our own microarray datasets. These datasets were derived from clinically relevant, AR-expressing tissues dissected from rodents treated with the full androgen dihydrotestosterone (DHT). Results. We found that there is a diverse response to DHT, with very little overlap of androgen regulated genes in each tissue. Gene ontology analyses also indicated that, while several tissues regulate similar biological processes in response to DHT, most androgen regulated processes are specific to one or a few tissues. Thus, it appears that the disparate physiological effects mediated by androgens begin with widely varying effects on gene expression in different androgen-sensitive tissues. Conclusion. The analysis completed in this study will lead to an improved understanding of how androgens mediate diverse, tissue-specific processes and better ways to assess the tissue-selective effects of AR modulators during drug development.Keywords
This publication has 41 references indexed in Scilit:
- Downregulation of Fzd6 and Cthrc1 and upregulation of olfactory receptors and protocadherins by dietary beta-carotene in lungs of Bcmo1−/− miceCarcinogenesis: Integrative Cancer Research, 2010
- Androgen-mediated improvement of body composition and muscle function involves a novel early transcriptional program including IGF1, mechano growth factor, and induction of β-cateninJournal of Molecular Endocrinology, 2009
- Castration-resistant prostate cancer: Targeting androgen metabolic pathways in recurrent diseaseUrologic Oncology, 2009
- Hormone therapy for endometriosis and surgical menopauseEmergencias, 2009
- Fine temporal analysis of DHT transcriptional modulation of the ATM/Gadd45g signaling pathways in the mouse uterusMolecular Reproduction and Development, 2008
- Androgen receptor expresion in breast cancer: Relationship with clinicopathological characteristics of the tumors, prognosis, and expression of metalloproteases and their inhibitorsBMC Cancer, 2008
- Selective androgen receptor modulators in preclinical and clinical developmentNuclear Receptor Signaling, 2008
- Visualizing Sexual Dimorphism in the BrainNeuron, 2004
- Linear Models and Empirical Bayes Methods for Assessing Differential Expression in Microarray ExperimentsStatistical Applications in Genetics and Molecular Biology, 2004
- Androgen receptors in the perinatal rat brainBrain Research, 1980