Concepedia

The Human Androgen Receptor: Complementary Deoxyribonucleic Acid Cloning, Sequence Analysis and Gene Expression in Prostate

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

Molecular Endocrinology · 1988 · 570 citations · 62 references

DOIFull text

Open access

Concepts

TL;DR

Androgenic hormones influence male development through a high‑affinity nuclear receptor, the human androgen receptor (hAR), which shares strong homology—especially in its DNA‑binding domain—with progesterone, mineralocorticoid, and glucocorticoid receptors. The authors generated rabbit polyclonal antibodies against a synthetic N‑terminal peptide of hAR to facilitate detection. The complete coding sequence of hAR was cloned, revealing a 919‑residue protein with 85 % homology to rat AR and identical DNA‑ and hormone‑binding domains; in human prostate, the predominant mRNA is 10 kb, and immunocytochemistry shows AR localized mainly in glandular epithelial nuclei.

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.

References

62

DNA sequencing with chain-terminating inhibitors

Frederick Sanger, S. Nicklen, Alan Coulson · Proceedings of the National Academy of Sciences · 1977

+20

69.1K citations

A simple method for displaying the hydropathic character of a protein

Jack Kyte, Russell F. Doolittle · Journal of Molecular Biology · 1982

+12

22.9K citations

Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease

John M. Chirgwin, Alan Przybyla, Raymond J. MacDonald et al. · Biochemistry · 1979

22.2K citations

A comprehensive set of sequence analysis programs for the VAX

John Devereux, Paul Haeberli, Oliver Smithies · Nucleic Acids Research · 1984

14.4K citations

8.4K citations