Benassayag C, Vallette G, Hassid J, Raymond J P, Nunez E A
Endocrinology. 1986 Jan;118(1):1-7. doi: 10.1210/endo-118-1-1.
Nonesterified fatty acids (NEFAs) have been recently shown in the rat to be involved in steroid hormone expression, having effects on plasma transport and intracellular activity. This study examines the influence of saturated and unsaturated NEFAs on estradiol (E2) binding to cytosol from human uterus, breast, and melanoma. Binding was analyzed after separation with dextran-coated charcoal or hydroxylapatite and by sucrose density gradient centrifugation. Unsaturated NEFAs induced a 2- to 10-fold increase (P less than 0.001) in E2 binding to cytosol from normal, fibromatous, and neoplastic uteri, while saturated NEFAs had a slight inhibitory effect (P less than 0.05). Similar effects were seen with cytosol from metastatic melanoma lymph nodes and neoplastic breast tissues. By contrast, unsaturated NEFAs did not increase E2 binding to serum from these patients. Density gradient centrifugation indicated that the increased binding was associated with the proteins present in the 2- to 4 S region. Analysis of E2 metabolites in the presence of unsaturated NEFAs showed the formation of water-soluble derivatives. Seventy percent of these E2 derivatives were trichloracetic acid precipitable, suggesting a covalent link between the steroid and a protein. The existence of such water-soluble metabolites could be erroneously interpreted as a true binding to soluble cytoplasmic receptors.
最近在大鼠中发现，非酯化脂肪酸（NEFAs）参与甾体激素的表达，对血浆转运和细胞内活性有影响。本研究考察了饱和及不饱和NEFAs对雌二醇（E2）与人子宫、乳腺及黑色素瘤细胞溶质结合的影响。用葡聚糖包被活性炭或羟基磷灰石分离后，通过蔗糖密度梯度离心法分析结合情况。不饱和NEFAs使E2与正常、纤维瘤性及肿瘤性子宫细胞溶质的结合增加2至10倍（P＜0.001），而饱和NEFAs有轻微抑制作用（P＜0.05）。转移性黑色素瘤淋巴结及肿瘤性乳腺组织的细胞溶质也有类似效应。相比之下，不饱和NEFAs并未增加E2与这些患者血清的结合。密度梯度离心表明，结合增加与2至4S区域的蛋白质有关。对不饱和NEFAs存在时E2代谢产物的分析显示形成了水溶性衍生物。这些E2衍生物的70%可被三氯乙酸沉淀，提示甾体与蛋白质之间存在共价连接。这种水溶性代谢产物的存在可能会被错误地解释为与可溶性细胞质受体的真正结合。
