衰老对正常及增生性人前列腺上皮和基质中5α-还原酶动力学参数的影响。

Effect of aging on kinetic parameters of 5 alpha-reductase in epithelium and stroma of normal and hyperplastic human prostate.

作者信息

Tunn S, Hochstrate H, Grunwald I, Flüchter S H, Krieg M

机构信息

Institute of Clinical Chemistry and Laboratory Medicine, University Clinic Bergmannsheil Bochum, West Germany.

出版信息

J Clin Endocrinol Metab. 1988 Nov;67(5):979-85. doi: 10.1210/jcem-67-5-979.

DOI:10.1210/jcem-67-5-979

PMID:2460487

Abstract

Altered 5 alpha-dihydrotestosterone (DHT) metabolism and stromal-epithelial cell interactions are two factors hypothesized to explain the development of benign prostatic hyperplasia (BPH). Furthermore, the development of BPH is clearly age dependent. Therefore, we studied the age-dependent alteration of 5 alpha-reductase, the enzyme that catalyzes the irreversible conversion of testosterone to DHT in epithelium and stroma of the human prostate. For this purpose kinetic parameters [Km Vmax] of 5 alpha-reductase were determined separately in epithelium and stroma of normal prostatic tissue (NPR) from 5 and BPH tissue from 20 men, and the results were correlated with the age of the donors (15-86 yr). The mean Km in epithelium [NPR, 14.3 +/- 1.8 (+/- SE); BPH, 29.5 +/- 2.7 nmol/L] was significantly (P less than 0.0001) lower than that in stroma (NPR, 78.4 +/- 8.5; BPH, 185.8 +/- 13.6 nmol/L). The mean Vmax in epithelium [NPR, 23.8 +/- 3.9 (+/- SE); BPH, 27.9 +/- 3.0 pmol/mg protein.h] was significantly (P less than 0.0001) lower than that in stroma (NPR, 68.3 +/- 4.4; BPH, 173.8 +/- 12.2 pmol/mg protein.h). The DHT-forming index (Vmax/Km) in NPR epithelium [1.6 +/- 0.2 (+/- SE)] was significantly (P less than 0.01) higher than that in NPR stroma (0.9 +/- 0.1), while in BPH the DHT-forming index was nearly identical in epithelium (1.1 +/- 0.1) and stroma (1.0 +/- 0.1). The Km values in epithelium and stroma both correlated positively (P less than 0.01) with age, but the Vmax values correlated positively with age (P less than 0.0001) only in stroma. The DHT-forming index decreased significantly with age in epithelium (P less than 0.01), but remained constant in stroma. These results indicate that there is a nonuniform age-dependent alteration of Km and Vmax in epithelium and stroma of the human prostate independent of the presence of BPH, which might have an impact on the conversion rate of testosterone to DHT with advancing age.

摘要

5α-二氢睾酮（DHT）代谢改变和基质-上皮细胞相互作用是被认为可解释良性前列腺增生（BPH）发病机制的两个因素。此外，BPH的发生明显与年龄相关。因此，我们研究了5α-还原酶随年龄的变化，该酶催化睾酮在人前列腺上皮和基质中不可逆地转化为DHT。为此，分别测定了20名男性正常前列腺组织（NPR）上皮和基质以及BPH组织中5α-还原酶的动力学参数[Km、Vmax]，并将结果与供体年龄（15 - 86岁）进行关联。上皮中的平均Km值[NPR，14.3±1.8（±SE）；BPH，29.5±2.7 nmol/L]显著低于基质（NPR，78.4±8.5；BPH，185.8±13.6 nmol/L）（P＜0.0001）。上皮中的平均Vmax值[NPR，23.8±3.9（±SE）；BPH，27.9±3.0 pmol/mg蛋白·小时]显著低于基质（NPR，68.3±4.4；BPH，173.8±12.2 pmol/mg蛋白·小时）（P＜0.0001）。NPR上皮中的DHT生成指数（Vmax/Km）[1.6±0.2（±SE）]显著高于NPR基质（0.9±0.1）（P＜0.01），而在BPH中，上皮（1.1±0.1）和基质（1.0±0.1）中的DHT生成指数几乎相同。上皮和基质中的Km值均与年龄呈正相关（P＜0.01），但只有基质中的Vmax值与年龄呈正相关（P＜0.0001）。上皮中的DHT生成指数随年龄显著下降（P＜0.01），但在基质中保持不变。这些结果表明，无论是否存在BPH，人前列腺上皮和基质中Km和Vmax随年龄的变化是不均匀的，这可能会随着年龄增长对睾酮向DHT的转化率产生影响。