[Androgen binding proteins in the rat prostate: methodological problems and regulation (author's transl)]

Area of Science:

• Endocrinology
• Molecular Biology
• Biochemistry

Context:

• Androgen receptor (AR) research is crucial for understanding hormone-dependent processes.
• Quantifying AR binding constants and site numbers provides insights into AR function.
• Hormonal regulation of AR dynamics is key to cellular responses.

Purpose:

• To develop and apply a selective assay for measuring androgen receptor binding constants.
• To characterize the binding affinity of dihydrotestosterone (DHT) and related androgens.
• To investigate the regulation and cellular localization of the androgen receptor.

Summary:

• Protamine sulfate precipitation quantifies AR equilibrium binding constants, determining DHT's association constant (1 x 10(9) 1/mole) and site number (11,500/cell).
• Androgen affinity correlates with biological activity; estradiol, progesterone, and antiandrogens compete for receptor binding.
• Nuclear AR complexes have a 3-hour half-life post-castration; cytosol AR levels decrease then spontaneously increase, suggesting testosterone regulates its own receptor synthesis and degradation. AR is localized to epithelial cells.

Impact:

• Establishes a method for precise AR binding quantification.
• Provides a basis for understanding androgen action and developing targeted therapies.
• Reveals dynamic regulation of AR levels and localization, impacting therapeutic strategies for hormone-related conditions.