Characterization of Prostate Cancer in a Functional Eunuch

Area of Science:

• Endocrinology
• Oncology
• Prostate Cancer Research

Background:

• Prostate cancer (CaP) is exceptionally rare in eunuchs, suggesting a critical role for androgens in its development.
• This study investigates a unique case of a 62-year-old functional eunuch who developed clinically localized CaP.

Observation:

• The patient, rendered eunuch by prepubertal mumps orchitis, presented with localized CaP.
• Serum and prostate tissue androgen levels were meticulously measured using liquid chromatography-tandem mass spectrometry.

Findings:

• Despite castrate serum testosterone and undetectable tissue testosterone, intracrine dihydrotestosterone (DHT) was synthesized within the prostate.
• Androgen receptor, androgen metabolism enzyme, and androgen-regulated genes were expressed in both CaP and benign prostate tissues, albeit at lower levels in CaP.
• DHT synthesis predominantly utilized the "backdoor" pathway, bypassing traditional androgen precursors like androstenedione and dehydroepiandrosterone.

Implications:

• This case challenges the established understanding of androgen requirements for CaP development.
• It highlights the potential for intracrine DHT production via alternative metabolic pathways, even in androgen-deficient states.
• Further research into the backdoor androgen synthesis pathway may reveal novel therapeutic targets for prostate cancer.