Review of studies on estrogen biosynthesis in the human.
Review of studies on estrogen biosynthesis in the human.
复制标题
人体雌激素生物合成研究综述。
作者：
P. Siiteri
虽然性腺和胎盘通常被认为是雌激素合成的主要部位，但现在已知许多其他组织也含有芳香酶。尽管有丰富的信息，但这种广泛分布的功能意义（如果有的话）尚不清楚。尽管如此，由于酶活性的明显增加或血液中底物可用性的增加而引起的雌激素产生升高对靶组织如乳房、子宫和骨骼有重要影响。我们早期的研究表明芳香化酶抑制剂可以有效地减少外周雌激素合成的影响，这已经被Santen和其他人的优雅研究充分证实。许多先前的研究表明芳香化酶活性可能存在于乳腺肿瘤中。对雌激素敏感肿瘤生长的深刻影响促使我们重新评估这个问题。使用我们最初的放射芳香酶测定的敏感修改，我们发现只有大约40%的人类乳腺肿瘤（n = 100）可检测到活性。只有很少（1/100）的芳香化酶活性超过1.0 pm/hr/g组织或人类胎盘中发现的0.001%。这些定量结果与一些已发表的报告相矛盾，这些报告表明大多数乳腺肿瘤含有生物学上显著水平的芳香酶活性。
While the gonads and placenta are usually thought of as the principal sites of estrogen synthesis, many other tissues are now known to contain the aromatase enzyme. Despite a wealth of information, the functional significance, if any, of this wide-spread distribution is not yet clear. Nonetheless, elevated estrogen production resulting from either an apparent increase in enzyme activity or increased substrate availability in blood can have important effects on target tissues such as the breast, uterus, and bone. Our early studies suggesting that aromatase inhibitors can effectively reduce the impact of peripheral estrogen synthesis have been amply confirmed by the elegant studies of Santen and others. Many previous studies have suggested that aromatase activity may be present in breast tumors. The profound implications for growth of estrogen-sensitive tumors led us to reevaluate this question. Using a sensitive modification of our original radiometric aromatase assay, we have found detectable activity in only about 40% of human breast tumors (n = 100). Only rarely (1/100) does the aromatase activity exceed 1.0 pm/hr/g tissue or 0.001% of that found in the human placenta. These quantitative results contradict several published reports which suggest that most breast tumors contain biologically significant levels of aromatase activity.