Effect of castration monotherapy on the levels of adrenal androgens in cancerous prostatic tissues

• Published in: Steroids Vol. 76; no. 3; pp. 301 - 308
• Main Authors: Arai, Seiji, Miyashiro, Yoshimichi, Shibata, Yasuhiro, Tomaru, Yukio, Kobayashi, Mikio, Honma, Seijiro, Suzuki, Kazuhiro
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier Inc 01.02.2011; Elsevier
• Subjects: Adrenal androgen; Adrenal Glands - metabolism; Androgens - analysis; Androgens - metabolism; Androstenediol - analysis; Androstenediol - metabolism; Androstenedione - analysis; Androstenedione - metabolism; Benign prostatic hyperplasia; Biological and medical sciences; Castration - methods; Chromatography, Liquid; Dehydroepiandrosterone - analysis; Dehydroepiandrosterone - metabolism; Dihydrotestosterone - analysis; Dihydrotestosterone - metabolism; Fundamental and applied biological sciences. Psychology; Gynecology. Andrology. Obstetrics; Humans; Liquid chromatography–tandem mass spectrometry; Male; Male genital diseases; Medical sciences; Nephrology. Urinary tract diseases; Prostate - metabolism; Prostate - pathology; Prostate - surgery; Prostate cancer; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - surgery; Prostatic Neoplasms - therapy; Solid-phase extraction; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Vertebrates: endocrinology; Adrenal androgen; Benign prostatic hyperplasia; Prostate cancer; Solid-phase extraction; Liquid chromatography–tandem mass spectrometry; Urinary system disease; Prostate disease; Androgen; Adrenal glands; Liquid chromatography-tandem mass spectrometry; Malignant tumor; Extraction; Benign neoplasm; Sex steroid hormone; Male genital diseases; Mass spectrometry; Cancer
• ISSN: 0039-128X; 1878-5867
• DOI: 10.1016/j.steroids.2010.12.001

▶ We developed an analytical method for quantifying DHEA, Adione, Adiol, T and DHT simultaneously. ▶ The levels of adrenal androgens in PCa tissues after ADT were similar to those in untreated PCa. ▶ DHEA was the most existing androgen precursor in PCa tissues after ADT. The mechanism accounting for the development of castration-resistant prostate cancer (CRPC) remains unclear. Studies in CRPC tissues suggest that, after androgen deprivation therapy (ADT), the adrenal androgens may be an important source of testosterone (T) and 5-alpha dihydrotestosterone (DHT) in CRPC tissues. To clarify the role of adrenal androgens in the prostatic tissues (prostatic tissue adrenal androgens) during ADT, we developed a high sensitive and specific quantification method for the levels of androgens in prostatic tissue using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Human prostatic tissues were purified using mixed-mode reversed-phase, strong anion exchange Oasis cartridges (Oasis MAX). Analysis of steroids was performed using LC–MS/MS after picolinic acid derivatization. The validation tests showed that our method of quantitative analysis was precise and sensitive enough for the quantification of dehydroepiandrosterone (DHEA), androstenedione, androstenediol, T, and DHT in the prostatic tissue. The levels of adrenal androgens in prostate cancer tissues after ADT were similar to those in untreated PCa. Especially, DHEA was the most existing androgen precursor in PCa tissues after ADT. The levels of DHEA were high in PCa tissues, irrespective of ADT. We assumed that DHEA played a significant role in the synthesis of T and DHT in PCa tissues after ADT.