Thijssen J H, Blankenstein M A
Department of Endocrinology, University Hospital, Utrecht, The Netherlands.
Eur J Cancer Clin Oncol. 1989 Dec;25(12):1953-9. doi: 10.1016/0277-5379(89)90377-5.
Because of a well-established mechanism of action, tissue concentrations of steroid hormones are thought to be more closely related than blood levels to the biological effects exerted by these hormones. The results of studies on oestrogen and androgen concentrations in malignant and normal breast tissues are presented. Normal fatty and epithelial breast tissues and malignant tumour samples which had been obtained from pre- and postmenopausal women of two countries (Poland and The Netherlands) differing in the incidence of this malignancy were studied. In both countries highly comparable oestradiol concentrations in the breast were found. The median hormone levels in tumour tissue of 0.65 pmol/g tissue did not change with age. They were significantly higher than in normal epithelial (0.48 and 0.25 pmol/g in pre- and postmenopausal women) and fatty tissues (0.54 and 0.19 pmol/g respectively). Particularly in postmenopausal women, hormone levels in tumour tissue were much higher than plasma concentrations, which are comparable in both populations. Oestrone levels decreased with age in normal and malignant breast tissues. In both countries median levels in normal and fatty tissues of premenopausal women were similar (1.10 pmol/g tissue) but higher than those in postmenopausal patients (0.45 pmol/g tissue. Significantly lower levels were found in the malignant tissue samples of Polish premenopausal women (0.70 pmol/g) than in Dutch women (1.05 pmol/g); similarly, after menopause the tissue concentrations were higher in Dutch (0.55 pmol/g) than in Polish (0.31 pmol/g) patients. Thus lower oestrone tissue levels were observed in tumours from the country with the lower incidence for breast cancer. In a comparable study of uterine tissues, obtained from pre- and postmenopausal women, higher oestradiol concentrations than in the breast were found, whereas estrone levels were very similar. The levels in the uterus did not correlate with those in the plasma; no relation with histology was observed. The results of androgen measurements in breast tissues were in agreement with the concept that, particularly, androstenedione and testosterone could play a role as substrates for local aromatization. Lower concentrations were observed in the tumours than in the normal and fatty tissues. More extensive investigations will be needed to clarify the role of local formation (aromatization, hydrolysis by sulphatase) of oestrogens in tissues and of the interconversion of less active (oestrone) to more active (oestradiol) oestrogens.
由于作用机制明确,人们认为类固醇激素的组织浓度比血液水平与这些激素所产生的生物学效应联系更为紧密。本文展示了对恶性和正常乳腺组织中雌激素和雄激素浓度的研究结果。研究对象为来自两个乳腺癌发病率不同的国家(波兰和荷兰)的绝经前和绝经后女性的正常脂肪和上皮乳腺组织以及恶性肿瘤样本。在这两个国家,均发现乳腺中雌二醇浓度具有高度可比性。肿瘤组织中激素水平的中位数为0.65 pmol/g组织,且不随年龄变化。它们显著高于正常上皮组织(绝经前和绝经后女性分别为0.48和0.25 pmol/g)和脂肪组织(分别为0.54和0.19 pmol/g)。特别是在绝经后女性中,肿瘤组织中的激素水平远高于血浆浓度,而这两个人群的血浆浓度具有可比性。在正常和恶性乳腺组织中,雌酮水平随年龄下降。在这两个国家,绝经前女性正常和脂肪组织中的中位数水平相似(1.10 pmol/g组织),但高于绝经后患者(0.45 pmol/g组织)。波兰绝经前女性的恶性组织样本中(0.70 pmol/g)的水平显著低于荷兰女性(1.05 pmol/g);同样,绝经后荷兰患者(0.55 pmol/g)的组织浓度高于波兰患者(0.31 pmol/g)。因此在乳腺癌发病率较低国家的肿瘤中观察到较低的雌酮组织水平。在一项对来自绝经前和绝经后女性的子宫组织的类似研究中,发现子宫中的雌二醇浓度高于乳腺,而雌酮水平非常相似。子宫中的水平与血浆中的水平无关;未观察到与组织学的关系。乳腺组织中雄激素测量的结果与以下概念一致,即特别是雄烯二酮和睾酮可能作为局部芳香化的底物发挥作用。在肿瘤中观察到的浓度低于正常和脂肪组织。需要进行更广泛的研究来阐明组织中雌激素的局部形成(芳香化、硫酸酯酶水解)以及活性较低的雌激素(雌酮)向活性较高的雌激素(雌二醇)的相互转化所起的作用。