Low systemic testosterone levels induce androgen maintenance in benign rat prostate tissue

Area of Science:

• Endocrinology
• Oncology
• Molecular Biology

Background:

• Prostate cancer (PC) risk increases with age, despite declining systemic androgen levels.
• Systemic androgens don't always reflect prostate tissue androgen levels, especially in metastatic PC.
• Age-related changes in prostate tissue androgen levels may contribute to tumorigenesis.

Purpose of the Study:

• To investigate if the rat prostate can maintain functional androgen levels despite low serum testosterone.
• To explore the relationship between serum and prostate androgen concentrations and androgen receptor (AR) signaling.
• To identify potential mechanisms by which the prostate regulates androgen levels.

Main Methods:

• Rats were castrated and implanted with capsules to control serum testosterone levels (castrate, sub-physiological, physiological, supra-physiological).
• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) quantified testosterone and dihydrotestosterone (DHT) in serum and prostate tissue.
• Quantitative reverse transcription polymerase chain reaction (RT-PCR) assessed androgen-regulated gene expression.

Main Results:

• Prostate tissue testosterone and DHT concentrations were similar across different serum testosterone levels.
• Androgen-regulated gene expression in the prostate remained consistent across treatment groups.
• Low-testosterone treatment altered androgen biosynthesis gene expression, suggesting a regulatory mechanism.

Conclusions:

• The rat prostate can maintain functionally active androgen levels independent of systemic testosterone fluctuations.
• This prostate-specific androgen regulation may play a role in age-related PC development.
• Altered expression of androgen biosynthesis genes indicates a mechanism for maintaining local androgen homeostasis.