Inhibition of estrogen biosynthesis and regression of mammary tumors by aromatase inhibitors.
Inhibition of estrogen biosynthesis and regression of mammary tumors by aromatase inhibitors.
复制标题
芳香酶抑制剂抑制雌激素生物合成和消退乳腺肿瘤。
DOI：
10.1007/978-1-4615-7192-6_11
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发表时间：
1981
影响因子：
--
通讯作者：
Wu,JT
中科院分区：
文献类型：
--
作者：
Brodie,AM;Brodie,HJ;Romanoff,L;Williams,JG;Williams,KI;Wu,JT
芳香酶抑制剂对雌激素依赖型癌症患者有潜在的治疗作用。这种方法的基本原理是，在所有产生雌激素的组织中，与芳香化酶相互作用的化合物可以提供选择性和有效的抑制。雄激素转化为雌激素是类固醇生物合成中的一种独特反应，因为它涉及类固醇分子A环的芳构化。这是从胆固醇到雌激素生物合成过程中的最后一系列步骤。因此，与那些影响类固醇合成早期步骤的化合物相比，抑制介导芳构化的酶系统的化合物有望成为更特异的雌激素生物合成抑制剂(Lipton和Santen，1974；Levin等人，1976)。在女性中，雌激素主要由卵巢产生，但性腺外组织(Longcope等人，1978；Hemsell等人，1974)，如脂肪、肌肉和某些乳腺肿瘤(Miller等人，1974；De Thibault等人，1974；Valera和Dao，1978)也合成雌激素，促进肿瘤生长。因此，作用于所有组织部位的芳香酶抑制剂可能比目前减少雌激素产生的方法更有效，也更具特异性。
Aromatase inhibitors are potentially useful therapeutic agents for patients with estrogen-dependent cancer. The rationale for this approach is that compounds interacting with aromatizing enzyme in all estrogen producing tissues could provide both selective and effective inhibition. The conversion of androgens to estrogens is a unique reaction in the biosynthesis of steroids since it involves aromatization of the A ring of the steroid molecule. This is the last series of steps in the biosynthetic progression from cholesterol to the estrogens. Therefore, compounds inhibiting the enzyme system mediating aromatization would be expected to be more specific inhibitors of estrogen biosynthesis than those influencing steps earlier in steroidogenesis (Lipton and Santen, 1974; Levin et al., 1976). In women, estrogens are produced primarily by the ovaries but extragonadal tissues (Longcope et al., 1978; Hemsell et al., 1974) such as fat, muscle and certain breast tumors (Miller et al., 1974; de Thibault et al., 1974; Valera and Dao, 1978) also synthesize estrogens which contribute to tumor growth. Thus, aromatase inhibitors acting in all tissue sites may be more effective as well as more specific than present methods for reducing estrogen production.