title: Human castration resistant prostate cancer rather prefer to decreased 5α-reductase activity.
abstract: Physiologically relevant steroid 5α-reductase (SRD5A) activity that is essential for dihydrotestosterone (DHT) biosynthesis in human castration-resistant prostate cancer (CRPC) has not been fully characterized yet. In this study to ascertain the potential SRD5A activity, we cultured two human CRPC cell lines, C4-2 and C4-2AT6, with the steroid precursor: ¹³C-[2,3,4]-androstenedione (13C-Adione), and analyzed the sequential biosynthesis of ¹³C-[2,3,4]-testosterone (13C-T) and ¹³C-[2,3,4]-DHT (13C-DHT) by liquid chromatography/mass spectrometry (LC/MS/MS). The 13C-DHT/13C-T concentration ratio detected by LC/MS/MS in C4-2AT6 cells appeared to reflect the SRD5A activity. The ratio in C4-2AT6 was significantly lower than that in C4-2. An increased concentration of DHT did not have a positive effect on cell proliferation, rather it exhibited inhibitory effects. 5α-reductase inhibitors did not have any inhibitory effect at clinically achievable concentrations. These results indicate that CRPC cells may have an unknown regulation system to protect themselves from an androgenic suppressive effect mediated by SRD5A activity.
authors: Department of Urology, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan.
authors: Takeo
authors: T
authors: Kosaka
authors: Akira
authors: A
authors: Miyajima
authors: Hirohiko
authors: H
authors: Nagata
authors: Takahiro
authors: T
authors: Maeda
authors: Eiji
authors: E
authors: Kikuchi
authors: Mototsugu
authors: M
authors: Oya
mesh_terms: D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000735:Androstenedione / Q000737:chemistry; D002247:Carbon Isotopes / Q000737:chemistry; D002369:Castration; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002851:Chromatography, High Pressure Liquid; D018920:Coculture Techniques; D013196:Dihydrotestosterone / Q000032:analysis / Q000378:metabolism; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000601:surgery; D012333:RNA, Messenger / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D013739:Testosterone / Q000032:analysis / Q000096:biosynthesis
chemical_list: D002247:Carbon Isotopes; D008565:Membrane Proteins; D012333:RNA, Messenger; D013196:Dihydrotestosterone; D013739:Testosterone; D000735:Androstenedione; D013741:3-Oxo-5-alpha-Steroid 4-Dehydrogenase; C548467:SRD5A1 protein, human; C548468:SRD5A2 protein, human