AROMATIZATION OF ANDROSTENEDIONE TO ESTRONE BY HUMAN ADIPOSE-TISSUE INVITRO - CORRELATION WITH ADIPOSE-TISSUE MASS, AGE, AND ENDOMETRIAL NEOPLASIA
AROMATIZATION OF ANDROSTENEDIONE TO ESTRONE BY HUMAN ADIPOSE-TISSUE INVITRO - CORRELATION WITH ADIPOSE-TISSUE MASS, AGE, AND ENDOMETRIAL NEOPLASIA
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DOI：
10.1210/jcem-53-1-192
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发表时间：
1981-01-01
影响因子：
5.8
通讯作者：
MACDONALD, PC
中科院分区：
文献类型：
--
作者：
FORNEY, JP;MILEWICH, L;MACDONALD, PC
为了探讨腺外雌激素形成与年龄、体重和子宫内膜肿瘤等临床参数之间的关系，建立了一种测定人脂肪组织中雄激素前体形成雌激素的速率的方法。底物，[3 H]雄烯二酮，是更有效的芳香化酶系统在这个组织中比[3 H]睾酮。雄激素转化为雌激素的最高速率发生在组织切片中，而不是在切碎或微粒体制剂中。在切片或切碎物中，不需要添加辅因子NADPH来进行芳构化，这可能是组织内源性产生NADPH的结果。当[3 H]雄烯二酮用作底物时，[3 H]雌酮是孵育中鉴定的唯一雌激素产物，而[3 H]雌二醇-17 β。当使用[3 H]睾酮时检测到的唯一雌激素。在组织切片中，由[3 H]雄烯二酮生成[3 H]雌酮的速率与孵育时间呈线性关系，直至孵育2 h，与组织质量呈线性关系，直至组织质量为1.0g。这些组织中芳香化酶活性的最适温度为37 ℃。C，脂肪组织芳香化酶对雄烯二酮的表观Km为0.25 μ M。还开发了一种方法来测量用于孵育的组织切片中的DNA含量。当从48名妇女，17名患有子宫内膜瘤的妇女和31名没有子宫内膜瘤的妇女的腹壁获得的脂肪组织中测量[3 H]雄烯二酮向[3 H]雌酮的转化率和DNA含量时，每单位质量脂肪组织（g）雄烯二酮转化为雌酮的速率与计算的脂肪组织的身体成分质量和计算的单位细胞数显著相关（106个细胞）存在于脂肪组织中。与年龄无关。从子宫内膜增生或癌的妇女获得的脂肪组织中雌酮的平均产生率显着高于从同等体重的妇女没有子宫内膜瘤。
To explore the relationship between extraglandular estrogen formation and the clinical parameters of age, weight and endometrial neoplasia, an assay was developed to measure the rate of estrogen formation from androgen precursors in human adipose tissue. The substrate, [3H]androstenedione, was more efficient than [3H]testosterone for the aromatase system in this tissue. The highest rate of conversion of androgen to estrogen occurred in tissue slices rather than in minces or microsomal preparations. The addition of cofactor NADPH was not required for aromatization in slices or minces, probably as a consequence of endogenous production of NADPH by the tissue. [3H]Estrone was the sole estrogenic product identified in incubations when [3H]androstenedione was used as the substrate, whereas [3H]estradiol-17.beta. was the exclusive estrogen detected when when using [3H]testosterone. The rate of [3H]estrone formation from [3H]androstenedione in tissue slices was linear with time of incubation up to 2 h and with tissue mass up to 1.0 g. The optimal temperature for aromatase activity in these tissues was 37.degree. C, and the apparent Km of adipose tissue aromatase for androstenedione was 0.25 .mu.M. A method was also developed to measure DNA content in the tissue slices used for incubation. When the conversion rates of [3H]androstenedione to [3H]estrone and DNA content were measured in adipose tissue obtained from the abdominal wall of 48 women, 17 women with and 31 women without endometrial neoplasia, the rate of conversion of androstenedione to estrone per unit mass of adipose tissue (g) correlated significantly with calculated body component mass of adipose tissue and with calculated unit cell number (106 cells) present in adipose tissue. There was no correlation with age. The mean rate of estrone production in the adipose tissue obtained from women with endometrial hyperplasia or carcinoma was significantly higher than that obtained from equivalent weight women without endometrial neoplasia.