Becker K F, Allmeier H, Höllt V
Department of Physiology, University of Munich, Germany.
Horm Metab Res. 1992 May;24(5):210-3. doi: 10.1055/s-2007-1003295.
P-glycoprotein, the product of the multidrug resistance (MDR1) gene, is an ATP-driven transmembrane pump that increases the resistance of cells by actively exporting toxic chemicals. In addition to transporting anticancer drugs, P-glycoprotein has been reported to extrude a variety of lipophilic drugs, such as calcium channel blockers, phenothiazines, cyclosporines etc. Interestingly, recent experiments suggest that steroid hormones may be physiologic substrates for P-glycoprotein. In addition, there exists a family of transporter genes with high structural homology to P-glycoprotein, the so-called ABC (ATP-binding casette) family. Although the physiological ligands for most of these transporters are unknown, there is increasing evidence that peptides may be transported by some of these proteins. Thus, the a-factor, a farnesylated pheromone with 13 amino acids, is exported from yeast cells by the product of the STE6 gene, a transporter protein with high homology to P-glycoprotein. Recently, we have cloned a novel member of the ABC-transporter gene family from neuroblastoma x glioma hybrid (NG-108-15) cells. This putative transporter gene ("NG-TRA") is expressed in the adrenal gland, kidney and in the brain. High amounts of NG-TRA mRNA are found in a variety of human brain tumors. Whether NG-TRA and/or other MDR-related transporters are involved in the transport of steroids, peptide hormones or growth factors remains to be established. If so, the cellular export of hormones by active pumps may represent a new mechanism of hormone secretion.
P-糖蛋白是多药耐药（MDR1）基因的产物，是一种由ATP驱动的跨膜泵，通过主动输出有毒化学物质来增加细胞的耐药性。除了转运抗癌药物外，据报道P-糖蛋白还能排出多种亲脂性药物，如钙通道阻滞剂、吩噻嗪类、环孢素等。有趣的是，最近的实验表明甾体激素可能是P-糖蛋白的生理底物。此外，还存在一个与P-糖蛋白具有高度结构同源性的转运蛋白基因家族，即所谓的ABC（ATP结合盒）家族。虽然这些转运蛋白中大多数的生理配体尚不清楚，但越来越多的证据表明某些蛋白质可能转运肽。因此，a因子是一种含13个氨基酸的法尼基化信息素，由STE6基因的产物从酵母细胞中输出，STE6基因是一种与P-糖蛋白具有高度同源性的转运蛋白。最近，我们从神经母细胞瘤x胶质瘤杂交（NG-108-15）细胞中克隆了ABC转运蛋白基因家族的一个新成员。这个假定的转运蛋白基因（“NG-TRA”）在肾上腺、肾脏和大脑中表达。在多种人类脑肿瘤中发现了大量的NG-TRA mRNA。NG-TRA和/或其他与多药耐药相关的转运蛋白是否参与甾体激素、肽类激素或生长因子的转运仍有待确定。如果是这样，主动泵对激素的细胞输出可能代表了一种新的激素分泌机制。
