Vermeulen A
Cancer Surv. 1986;5(3):585-95.
Oestrogen-progesterone imbalance in favour of the oestrogens is considered to be an important factor in the development of mammary cancer, although oestrogens are not directly mitogenic. Moreover, this promoter effect of carcinogenesis may be limited in time. Except for increased plasma (free) oestradiol levels, plasma sex hormone levels in breast cancer patients are comparable to those in normal women, matched for age and weight. In both benign and malignant breast tissue, sex hormone concentrations (ng/g) are significantly higher than in plasma (ng/mg), except for dehydroepiandrosterone sulphate, oestrone sulphate and testosterone, but in breast cancer tissues, dehydroepiandrosterone sulphate (DHEAS), 5 alpha-androstane-3 alpha-17 beta-diol and progesterone concentrations are lower than in normal breast tissue. As to the origin of these sex hormones in breast tissue, a positive arteriovenous gradient across the breast tissue has been observed for androstenedione and oestradiol, suggesting uptake from plasma by the tissues. Aromatization of androstenedione, on the other hand, is probably only a minor source of oestrogens in breast tissue. Hydrolysis of oestrone sulphate taken up from the blood, or oestradiol-17 beta fatty acid esters may be another source, but data are too scarce at present to draw a final conclusion as to their role as source of tissue oestrogens. 17 beta-hydroxysteroid dehydrogenase activity, inactivating oestradiol into oestrone, may be an important determinant of tissue oestradiol concentration. This enzyme activity was found to be higher in oestrogen receptor positive than in oestrogen receptor negative tissues and was negatively correlated with DHEA and DHEAS concentrations. As it was shown that the latter two steroids are non-competitive inhibitors of the 17 beta-hydroxysteroid dehydrogenase as well as of the oestrogen-sulphotransferase, it appears that DHEA may be an important modulator of tissue oestradiol concentration, whereas the 17 beta-hydroxysteroid dehydrogenase might constitute an additional marker of hormone dependency of breast cancer.
雌激素与孕激素失衡且雌激素占优势被认为是乳腺癌发生发展的一个重要因素，尽管雌激素并非直接具有促有丝分裂作用。此外，这种致癌的启动效应可能在时间上是有限的。除了血浆（游离）雌二醇水平升高外，乳腺癌患者的血浆性激素水平与年龄和体重匹配的正常女性相当。在良性和恶性乳腺组织中，性激素浓度（ng/g）均显著高于血浆（ng/mg），硫酸脱氢表雄酮、硫酸雌酮和睾酮除外，但在乳腺癌组织中，硫酸脱氢表雄酮（DHEAS）、5α-雄烷-3α-17β-二醇和孕酮浓度低于正常乳腺组织。关于乳腺组织中这些性激素的来源，已观察到雄烯二酮和雌二醇在乳腺组织中存在正向动静脉梯度，提示组织从血浆中摄取。另一方面，雄烯二酮的芳香化作用可能只是乳腺组织中雌激素的一个次要来源。从血液中摄取的硫酸雌酮或雌二醇-17β脂肪酸酯的水解可能是另一个来源，但目前数据太少，无法就它们作为组织雌激素来源的作用得出最终结论。17β-羟类固醇脱氢酶活性可将雌二醇转化为雌酮，可能是组织雌二醇浓度的一个重要决定因素。发现该酶活性在雌激素受体阳性组织中高于雌激素受体阴性组织，且与脱氢表雄酮（DHEA）和硫酸脱氢表雄酮（DHEAS）浓度呈负相关。由于已表明后两种类固醇是17β-羟类固醇脱氢酶以及雌激素磺基转移酶的非竞争性抑制剂，似乎DHEA可能是组织雌二醇浓度的重要调节剂，而17β-羟类固醇脱氢酶可能构成乳腺癌激素依赖性的另一个标志物。
