AROMATASE INHIBITORS, BREAST CANCER, AND OTHER DISEASES

在以前的研究中，4-羟基雄烯二酮(4-OHA)被发现是一种 雌激素生物合成的有效抑制因子。该化合物可降低雌激素。 并能使DMBA诱发的大鼠乳腺肿瘤消退。它 现建议对绝经后乳腺癌患者的4-OHA进行评估 在雌激素起作用的其他疾病的患者中也是如此。 最新发现4-OHA和其他类固醇芳香酶抑制剂导致 该酶的失活将通过动力学和 放射性标记技术。将使用放射性标记的芳香酶抑制剂 测定芳香酶的半衰期和结合位点数。 描述了研究4-OHA的不同效应 子宫和DMBA诱发的大鼠乳腺肿瘤。组织重量， 胞质和胞核的雌激素受体和孕激素受体将 量化的。据报道，血清雌二醇水平在 患有心肌梗塞和心绞痛的男性。芳香酶抑制剂治疗 可能对有心肌梗塞风险的患者有价值，如果 雌二醇在这种疾病中很重要。以确定是否增加了 患者体内的雌二醇量增加或清除量减少。 雌二醇、外周芳构化和代谢清除率 雌二醇将被测量，以及患者的血浆浓度。 如果血液水平的升高是由于产量的增加，研究 会调查雌二醇是否有任何病因 通过测定雌激素受体的浓度在疾病中的作用 人心脏和血管组织及雌二醇对其影响 冠状动脉的平滑肌层。影响芳构化反应的各种因素 外周组织也将在体外进行研究。

In previous studies 4-hydroxyandrostenedione (4-OHA) was found to be a potent inhibitor of estrogen biosynthesis. The compound reduces estrogen secretion and caused regression of DMBA-induced mammary tumors in rats. It is now proposed to evaluate 4-OHA in postmenopausal breast cancer patients and also in patients with other diseases in which estrogen plays a role. Recent findings that 4-OHA and other steroidal aromatase inhibitors cause inactivation of the enzyme will be investigated by kinetic and radiolabeling techniques. Radiolabeled aromatase inhibitor would be used to determine the half-life and number of binding sites of aromatase. Studies are described to investigate the differential effect of 4-OHA on the uterus and DMBA-induced mammary tumors of the rat. Tissue weight, cytosolic and nuclear estrogen receptors and progesterone receptors will be quantitated. Serum estradiol levels have been reported to be increased in men with myocardial infarction and angina. Aromatase inhibitor treatment might be of value in patients at risk for myocardial infarction if estradiol is important in this disease. To determine whether increased estradiol in patients is due to increased production or reduced clearance of estradiol, peripheral aromatization and metabolic clearance rate of estradiol would be measured as well as plasma concentrations in patients. If the increase in blood level is due to increased production, studies would be undertaken to investigate whether estradiol has any etiological role in the disease by determining concentrations of estrogen receptors in human heart and vascular tissue and the effect of estradiol on isolated coronary artery smooth muscle. Various factors affecting aromatization in peripheral tissue will also be investigated in vitro.