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Molecular Endocrinology Vol. 2, No. 12 1265-1275
doi:10.1210/mend-2-12-1265
Copyright © 1988 by the Endocrine Society.
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The Human Androgen Receptor: Complementary Deoxyribonucleic Acid Cloning, Sequence Analysis and Gene Expression in Prostate

Dennis B. Lubahn, David R. Joseph, Madhabananda Sar, Jiann-an Tan, Henry N. Higgs, Robert E. Larson, Frank S. French and Elizabeth M. Wilson

Laboratories for Reproductive Biology, and the Department of Pediatrics, Physiology, University of North Carolina at Chapel Hill Chapel Hill, North Carolina 27599
Department of Cell Biology and Anatomy, University of North Carolina at Chapel Hill Chapel Hill, North Carolina 27599
Department of Biology, University of North Carolina at Chapel Hill Chapel Hill, North Carolina 27599
Department of Biochemistry, University of North Carolina at Chapel Hill Chapel Hill, North Carolina 27599

Address requests for reprints to: Dr. Elizabeth M. Wilson, Laboratories for Reproductive Biology, CB#7500 MacNider Building, 202H, University of North Carolina, Chapel Hill, North Carolina 27599.

Abstract

Androgenic hormones mediate their effects on male sex differentiation and development through a high affinity receptor protein. We report here cloning of the complete coding sequence of the human androgen receptor (hAR). By sequence homology hAR is a member of the nuclear receptor family, with closest sequence identity to the progesterone, mineralocorticoid, and glucocorticoid receptors. Regions of highest homology include the DNA-binding domain and a small region within the hydrophobic ligand-binding domain. Comparison of the deduced 919 amino acid sequence of hAR (98,999 mol wt) to the 902 amino acid sequence of rat AR (98,227 mol wt) reveals identical sequences in the DNA- and hormone-binding domains, with an overall homology of 85%. In human prostate, the major androgen receptor mRNA species is 10 kilobases while a less abundant mRNA is approximately 7 kilobases. Rabbit polyclonal antibodies were raised against a synthetic peptide from the N-terminal region of hAR. Immunocytochemical analysis of human prostate tissue demonstrated that AR is localized predominantly in nuclei of glandular epithelial cells.

FOOTNOTES

Supported by Grants HD-16910, HD-04466, HD-21744, and P30-HD-18968 (recombinant DNA and histochemistry cores) from the National Institute of Child Health and Human Development Center for Population Research, and by NIH Grants NS-17479, T32-DK-07219, and by the Andrew W. Mellon Foundation.

Received for publication July 20, 1988. Accepted for publication August 22, 1988.




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