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竞争性逆转录-聚合酶链反应分析表明,女性臀部、大腿和腹部脂肪组织中芳香化酶细胞色素P450转录本水平随年龄增长而升高。

Competitive reverse transcription-polymerase chain reaction analysis indicates that levels of aromatase cytochrome P450 transcripts in adipose tissue of buttocks, thighs, and abdomen of women increase with advancing age.

作者信息

Bulun S E, Simpson E R

机构信息

Cecil H. and Ida Green Center for Reproductive Biology Sciences, Department of Obstetrics-Gynecology, University of Texas Southwestern Medical Center, Dallas 75235-9051.

出版信息

J Clin Endocrinol Metab. 1994 Feb;78(2):428-32. doi: 10.1210/jcem.78.2.8106632.

Abstract

Circulating androstenedione is converted to estrone in adipose tissue, which is the principal site of estrogen biosynthesis in postmenopausal women. This reaction is catalyzed by a specific form of cytochrome P450 (P450arom; the product of the CYP19 gene). The fractional conversion of plasma androstenedione to estrone as well as the specific activity of aromatase in adipose stromal cells were previously shown to increase with advancing age. To determine whether this positive effect of aging on estrogen biosynthesis is due to an alteration in tissue levels of P450arom transcripts, we quantified P450arom mRNA levels in sc fat biopsy samples (n = 33) from buttocks, thighs, and abdomen of 11 women who ranged in age from 23-61 yr. Competitive polymerase chain reaction linked to reverse transcription was used to quantify P450arom transcripts in total RNA that was isolated from sc fat obtained by needle aspiration. In each sample, primer extension and coamplification of a rat P450arom cRNA as an internal standard were used to control possible differences in amplification efficiencies between samples. The results demonstrate that with advancing age in women, there is a progressive and statistically significant increase in adipose tissue P450arom transcript levels (normalized to total RNA content) in buttocks, thighs, and abdomen (correlation coefficients: r = 0.704, 0.854, and 0.933, respectively). The levels of transcripts observed in the older subjects reach 2- to 4-fold greater than those observed in the young women. Adipose tissue P450arom transcript levels were highest in the buttocks, followed by the thighs, and lowest in the abdomen. This increase in P450arom transcript levels is likely to be a major factor contributing to the increased extragonadal estrogen biosynthesis in elderly women.

摘要

循环中的雄烯二酮在脂肪组织中转化为雌酮,脂肪组织是绝经后女性雌激素生物合成的主要部位。该反应由一种特定形式的细胞色素P450(P450arom;CYP19基因的产物)催化。先前研究表明,血浆雄烯二酮向雌酮的转化率以及脂肪基质细胞中芳香化酶的比活性会随着年龄的增长而增加。为了确定衰老对雌激素生物合成的这种积极影响是否归因于P450arom转录本的组织水平改变,我们对11名年龄在23至61岁之间女性的臀部、大腿和腹部皮下脂肪活检样本(n = 33)中的P450arom mRNA水平进行了定量。采用逆转录竞争性聚合酶链反应来定量从针吸获得的皮下脂肪中分离出的总RNA中的P450arom转录本。在每个样本中,使用大鼠P450arom cRNA作为内标进行引物延伸和共扩增,以控制样本间扩增效率的可能差异。结果表明,随着女性年龄的增长,臀部、大腿和腹部的脂肪组织P450arom转录本水平(相对于总RNA含量进行标准化)呈渐进性且具有统计学意义的增加(相关系数分别为:r = 0.704、0.854和0.933)。老年受试者中观察到的转录本水平比年轻女性中观察到的高出2至4倍。脂肪组织P450arom转录本水平在臀部最高,其次是大腿,在腹部最低。P450arom转录本水平的这种增加可能是导致老年女性性腺外雌激素生物合成增加的主要因素。

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