title: Development of 17β-hydroxysteroid dehydrogenase type 3 as a target in hormone-dependent prostate cancer therapy.
abstract: 17β-Hydroxysteroid dehydrogenase type 3 (17β-HSD3) is expressed almost exclusively in the testes and specifically converts the weak androgenic androstenedione to active testosterone (T) in the presence of NADPH. Additionally, studies have demonstrated that 17β-HSD3 is over-expressed in hormone-dependent prostate cancer. T, which interacts with the androgen receptor (AR), eventually stimulates the growth of prostate cancer cells. Defects in T synthesis or action impair the development of the male phenotype during embryogenesis and cause the autosomal recessive disorder male pseudohermaphroditism. Affected individuals are often born with female-appearing external genitalia and are reared as females. Since 17β-HSD3 plays a central role in T production, it has been recognized as a promising therapeutic target to reduce the circulating level of androgens and to suppress androgen-sensitive tumor proliferation. In recent decades, improvements have been made in the development of 17β-HSD3 inhibitors. Herein, we give an overview of the main structure and function of human 17β-HSD3 and summarize steroidal and non-steroidal inhibitors of 17β-HSD3, which can be a potential target for prostate cancer.
authors.affiliation: Institute of Materia Medica and Guangdong Provincial Key Laboratory of New Pharmaceutical Dosage Form, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, PR China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Ning
authors.affiliation: Institute of Biomedicine and Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, Guangdong 510632, PR China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Materia Medica and Guangdong Provincial Key Laboratory of New Pharmaceutical Dosage Form, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, PR China.
authors.forename: Hong
authors.initials: H
authors.lastname: Deng
authors.affiliation: Institute of Biomedicine and Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, Guangdong 510632, PR China.
authors.forename: Qihao
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute of Biomedicine and Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, Guangdong 510632, PR China.
authors.forename: Yadong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Institute of Biomedicine and Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, Guangdong 510632, PR China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Su
authors.affiliation: Sinopharm Group Guangdong Medi-world Pharmaceutical Co. Ltd., Foshan 528200, PR China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Institute of Biomedicine and Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou, Guangdong 510632, PR China. Electronic address: txiangqi@jnu.edu.cn.
authors.forename: Qi
authors.initials: Q
authors.lastname: Xiang
authors.affiliation: Institute of Materia Medica and Guangdong Provincial Key Laboratory of New Pharmaceutical Dosage Form, Guangdong Pharmaceutical University, Guangzhou, Guangdong 510006, PR China. Electronic address: zzss_97@163.com.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhang
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000378:metabolism; D013739:Testosterone / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D013739:Testosterone; D015067:17-Hydroxysteroid Dehydrogenases; C476565:17beta-hydroxysteroid dehydrogenase type 3
keywords: 17β-Hydroxysteroid dehydrogenase type 3; Hormone-dependent prostate cancer; Inhibitor; Testosterone