Microarray analysis of androgen-regulated gene expression in testis: the use of the androgen-binding protein (ABP)-transgenic mouse as a model

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  • Petrusz, Peter
    • Affiliation: School of Medicine, Department of Cell Biology and Physiology
    • Other Affiliation: Laboratories for Reproductive Biology
  • Jeyaraj, Durairaj A
    • Affiliation: School of Medicine, Department of Cell Biology and Physiology
    • Other Affiliation: Laboratories for Reproductive Biology
  • Grossman, Gail
    • Affiliation: School of Medicine, Department of Cell Biology and Physiology
    • Other Affiliation: Laboratories for Reproductive Biology
Abstract
  • Background Spermatogenesis is an androgen-dependent process, yet the molecular mechanisms of androgens' actions in testis are poorly understood. Transgenic mice overexpressing rat androgen-binding protein (ABP) in their testes have reduced levels of intratesticular androgens and, as a result, show a progressive impairment of spermatogenesis. We used this model to characterize changes in global gene expression in testis in response to reduced bioavailability of androgens. Methods Total RNA was extracted from testes of 30-day old transgenic and wild-type control mice, converted to cRNA, labeled with biotin, and hybridized to oligonucleotide microarrays. Microarray results were confirmed by real-time reverse transcription polymerase chain reaction. Results Three-hundred-eighty-one genes (3.05% of all transcripts represented on the chips) were up-regulated and 198 genes (1.59%) were down-regulated by at least a factor of 2 in the androgen-deficient animals compared to controls. Genes encoding membrane proteins, intracellular signaling molecules, enzymes, proteins participating in the immune response, and those involved in cytoskeleton organization were significantly overrepresented in the up-regulated group. Among the down-regulated transcripts, those coding for extracellular proteins were overrepresented most dramatically, followed by those related to proteolysis, cell adhesion, immune response, and growth factor, cytokine, and ion channel activities. Transcripts with the greatest potential impact on cellular activities included several transcription factors, intracellular signal transducers, secreted signaling molecules and enzymes, and various cell surface molecules. Major nodes in the up-regulated network were IL-6, AGT, MYC, and A2M, those in the down-regulated network were IL-2, -4, and -10, MAPK8, SOCS1, and CREB1. Conclusion Microarray analysis followed by gene ontology profiling and connectivity analysis identified several functional groups of genes and individual genes responding to sustained reduction of androgen levels in the mouse testis. These include genes whose products function as transcription factors, cell surface molecules including ion channels, extra- and intracellular signaling molecules, and secreted enzymes with the potential of regulating cell-to-cell attachment. The transcription factors CREB1 (down-regulated) and MYC (up-regulated) may mediate the most important initial phases of the testicular response to reduced levels of androgens. These results suggest specific avenues for further research that will lead to a better understanding of how androgens regulate spermatogenesis.
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  • Article
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  • In Copyright
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  • Peter Petrusz et al.; licensee BioMed Central Ltd.
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Journal title
  • Reproductive Biology and Endocrinology
Journal volume
  • 3
Journal issue
  • 1
Page start
  • 70
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1477-7827
Bibliographic citation
  • Reproductive Biology and Endocrinology. 2005 Dec 09;3(1):70
Publisher
  • BioMed Central Ltd
Access right
  • Open Access
Date uploaded
  • September 5, 2012

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file details 1477-7827-3-70.pdf 2019-05-06 Public Download
file details This file is a Table listing all of the 198 genes whose expression was down-regulated by a factor of 2 or more in the testes of ABP-transgenic mice as compared to controls. 2019-05-06 Public Download
file details This is a Table listing all of the 381 genes whose expression was up-regulated by a factor of 2 or more in the testes ABP-transgenic mice as compared to controls. 2019-05-06 Public Download
file details 1477-7827-3-70.xml 2019-05-06 Public Download