Characterization of Prostate Cancer in a Functional Eunuch

Abstract

Background Eunuchs rarely, if ever, develop prostate cancer (CaP). This article reports on a 62-year-old functional eunuch from prepubertal mumps orchitis who developed clinically localized CaP. Methods Serum and CaP and benign prostate tissue androgen levels were measured using a validated liquid chromatography-tandem mass spectrometry assay. The assay measures testosterone; dihydrotestosterone (DHT); the adrenal androgens, androstenedione and dehydroepiandrosterone; and the androgen metabolites, androsterone and androstanedione. Gene and protein expression levels of androgen metabolism enzymes, and androgen receptor and androgen-regulated genes were measured using quantitative reverse-transcription polymerase chain reaction and immunohistochemistry, respectively. Results Intracrine androgen metabolism produced tissue DHT when serum and tissue testosterone levels were castrate and undetectable, respectively. Androgen receptor, androgen-regulated, and androgen metabolism enzyme genes were expressed but at lower levels in CaP than benign tissues. Conclusions DHT was synthesized using the primary backdoor androgen metabolism pathway and not using androstenedione or dehydroepiandrosterone via the frontdoor or secondary backdoor pathways.

Serum‐free complete medium, an alternative medium to mimic androgen deprivation in human prostate cancer cell line models

“…Therefore, LC‐MS/MS was performed to determine if media composition impacted T metabolism. LAPC‐4 cells were used because LAPC‐4 cells express SRD5A enzymes that metabolize T to DHT (Figure A, modified from ), unlike LNCaP or C4‐2 cells, which cannot metabolize T to DHT . LC‐MS/MS revealed that LAPC‐4 cells cultured for 6 days in CM alone produced higher levels of DHT (all P ‐values <0.05; Supplemental Table S5) than LAPC‐4 cells cultured for 6 days in SFM or CSM alone (Figures B and C, and Supplemental Table S5).…”

Mathematical modeling of intracrine androgen metabolism in prostate cancer: Methodological aspects

“…CRPC is driven in part by DHT derived from intratumoral metabolism of adrenal androgens . DHT biosynthesis involves three androgen biosynthesis pathways (Figure , modified from). In the frontdoor pathway, the adrenal androgens (dehydroepiandrosterone [DHEA] and androstenedione [ASD]) are T precursors, and T is reduced by 5α‐reductases (SRD5A) to form DHT.…”

“…Androgen biosynthesis pathways (modified from). Prostate cancer (CaP) cells can produce dihydrotestosterone (DHT) via three androgen biosynthesis pathways.…”

Sexual steroids in serum and prostatic tissue of human non‐cancerous prostate (STERPROSER trial)

“…They found a significant positive correlation between the local prostatic serum DHT levels and both prostate weight and peripheral serum levels. As prostate cancer is able to synthesize DHT in an intracrine manner, the presence of cancer could lead to biased assessments. For this reason, study regarding relationship between sex steroid concentrations and prostate enlargement requires exclusion of the presence of cancer through a complete pathological examination.…”