Physicochemical characterization of the androgen receptor from hyperplastic human prostate

Area of Science:

• Endocrinology
• Molecular Biology
• Urology

Background:

• Benign prostatic hyperplasia (BPH) is a common condition in aging men.
• Androgen receptor (AR) plays a critical role in the development and progression of BPH.
• Understanding AR characteristics in BPH tissue is crucial for targeted therapies.

Purpose of the Study:

• To characterize the biochemical and biophysical properties of the androgen receptor (AR) in human benign prostatic hypertrophied (BPH) tissue.
• To determine the binding affinity and specificity of the AR for various androgens and related steroids.
• To investigate the structural and functional characteristics of the AR in BPH.

Main Methods:

• Cytosol from BPH tissue was labeled with radioligands to identify specific androgen receptor sites.
• An exchange assay was developed to determine binding affinity (Kd) and capacity.
• Sedimentation analysis, gel filtration, and chromatofocusing were used to characterize receptor properties.

Main Results:

• A high-affinity androgen receptor was detected with a Kd of 1.3 +/- 0.8 nM and a binding capacity of 15 +/- 7 fmol/mg protein.
• The receptor exhibited high specificity for androgens, with R1881 showing the highest affinity (Ki = 0.09 nM).
• Biophysical analysis indicated a sedimentation coefficient of 4.1 S, a Stokes radius of 6.5 nm, and a Mr of 120,000.

Conclusions:

• Benign prostatic hypertrophied (BPH) tissue contains an androgen receptor (AR) with high affinity and specificity for androgens.
• The characterized AR in BPH tissue shares similarities with ARs found in other androgen-responsive tissues.
• These findings contribute to understanding the role of AR in BPH pathogenesis and may inform therapeutic strategies.