Estrogen formation in human prostatic tissue from patients with and without benign prostatic hyperplasia.
Estrogen formation in human prostatic tissue from patients with and without benign prostatic hyperplasia.
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患有或不患有良性前列腺增生的患者前列腺组织中雌激素的形成。
DOI：
10.1002/pros.2990090402
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Fishman,J
中科院分区：
文献类型：
--
作者：
Stone,NN;Fair,WR;Fishman,J
在膀胱切除术时切除的前列腺组织被分成尿道周围和外周区。在存在或不存在芳香酶抑制剂4-羟基雄烯二酮（4-OHAD）和5α-还原酶抑制剂4-MA（N，N-二乙基-4-甲基-3-氧代-4-氮杂-5 α-雄烷17β-甲酰胺）的情况下，将匀浆组织与[1，2，6，73 H]雄烯二酮一起孵育。通过[3 H]雌酮和[3 H]雌二醇的反向同位素稀释并结晶至恒定比活度来测定雌激素形成。使用加热的前列腺组织平行进行对照孵育。良性前列腺增生（BPH）患者尿道周围区产生的总雌激素为223 fmol/ mg蛋白/hr（SE ± 57），而非BPH患者为102 fmol（SE ± 17）。前列腺增生患者外周带雌激素生成量为175 fmol（SE ± 69），正常患者外周带雌激素生成量为105 fmol（SE ± 26）。前列腺芳香化酶表现出Michaelis门顿动力学，表观Km为90 nM。4-OHAD抑制前列腺组织芳构化57 - 93%。芳构化也被4-MA强烈抑制，表明4-MA是该组织中有效的芳香酶以及5α-还原酶抑制剂。这些结果表明，雄激素的芳构化雌激素在人类前列腺的进展在一个相当大的速度和局部雌激素的形成可能预先存在，并在BPH和前列腺癌的病因因素。
Prostatic tissue removed at the time of cystoprostatectomy was separated into periurethral and peripheral zones. Homogenized tissue was incubated with [1,2,6,73H] androstenedione in the presence or absence of an aromatase inhibitor, 4‐hydroxyandrostenedione (4‐OHAD) and a 5α‐reductase inhibitor 4‐MA (N,N‐diethyl‐4‐methyl‐3‐oxo‐4‐aza‐5α‐androstane 17β‐carboxamide). Estrogen formation was determined by reverse isotope dilution of [3H] estrone and [3H] estradiol and crystallization to constant specific activity. Control incubations were carried out in parallel utilizing heated prostatic tissue. Total estrogens produced in the periurethral zone in patients with benign prostatic hyperplasia (BPH) was 223 fmol/ mg protein/hr (SE ± 57) compared to 102 fmol (SE ± 17) in patients without BPH. Estrogen formation in the peripheral zone was 175 fmol (SE ± 69) and 105 fmol (SE ± 26) in patients with and without BPH, respectively. The prostatic aromatase exhibits Michaelis‐Menton kinetics with an apparent Km of 90 nM. 4‐OHAD inhibited aromatization in the prostatic tissue by 57‐93%. Aromatization was also strongly inhibited by 4‐MA, indicating that 4‐MA is a potent aromatase as well as a 5α‐reductase inhibitor in this tissue. These results suggest that aromatization of androgens to estrogens in the human prostate proceeds at a substantial rate and that local estrogen formation could preexist and be a factor in the etiology of BPH and prostatic cancer.