Zhu Yuan-Shan, Imperato-McGinley Julianne L
Division of Endocrinology, Department of Medicine, Weill Cornell Medical College, New York, New York 10065, USA.
Ann N Y Acad Sci. 2009 Feb;1155:43-56. doi: 10.1111/j.1749-6632.2009.04115.x.
Androgens acting via the androgen receptor play critical roles in prostate development, growth, and pathogenesis. There are two potent androgens, testosterone and dihydrotestosterone (DHT), in humans and mammals. DHT is converted from testosterone by 5alpha-reductase isozymes. Two 5alpha-reductase isozymes have been identified. Although both isozymes are expressed, 5alpha-reductase-2 is the predominant isozyme in the human prostate. Mutations in 5alpha-reductase-2 gene cause the 5alpha-reductase-2 deficiency syndrome. Affected 46, XY individuals have a small, nonpalpable, and rudimentary prostate in adulthood. Neither benign prostate hyperplasia (BPH) nor prostate cancer has been reported in these patients. The prostate is small in animals with 5alpha-reductase-2 gene knockout or treated with specific 5alpha-reductase inhibitors. 5alpha-reductase isozymes are molecular targets for the prevention and treatment of BPH and prostate cancer. Moreover, androgen actions on prostate gene expression and cell growth are directly modulated by estrogen receptor ligands via protein-protein interactions. The studies of 5alpha-reductases and androgen actions highlight the importance of 5alpha-reductase isozymes in male sexual differentiation and prostate physiology and pathophysiology.
雄激素通过雄激素受体发挥作用，在前列腺的发育、生长和发病机制中起着关键作用。在人类和哺乳动物体内有两种强效雄激素，即睾酮和双氢睾酮（DHT）。DHT由5α-还原酶同工酶将睾酮转化而来。已鉴定出两种5α-还原酶同工酶。虽然两种同工酶均有表达，但5α-还原酶-2是人类前列腺中的主要同工酶。5α-还原酶-2基因突变会导致5α-还原酶-2缺乏综合征。受影响的46, XY个体在成年后前列腺小、触诊不到且发育不全。这些患者中均未报告有良性前列腺增生（BPH）或前列腺癌。在5α-还原酶-2基因敲除的动物或用特定5α-还原酶抑制剂治疗的动物中，前列腺较小。5α-还原酶同工酶是预防和治疗BPH及前列腺癌的分子靶点。此外，雌激素受体配体通过蛋白质-蛋白质相互作用直接调节雄激素对前列腺基因表达和细胞生长的作用。对5α-还原酶和雄激素作用的研究突出了5α-还原酶同工酶在男性性分化以及前列腺生理和病理生理中的重要性。
