Title: | New mechanisms of hormone secretion: MDR-like gene products as extrusion pumps for hormones? |
Author(s): | Becker KF; Allmeier H; Hollt V; |
Address: | "Department of Physiology, University of Munich, Germany" |
ISSN/ISBN: | 0018-5043 (Print) 0018-5043 (Linking) |
Abstract: | "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" |
Keywords: | "ATP Binding Cassette Transporter, Subfamily B, Member 1 ATP-Binding Cassette Transporters/chemistry/*genetics Amino Acid Sequence Animals Drug Resistance/*genetics Hormones/*metabolism/physiology Humans Membrane Glycoproteins/chemistry/*genetics Molecular;" |
Notes: | "MedlineBecker, K F Allmeier, H Hollt, V eng Review Germany 1992/05/01 Horm Metab Res. 1992 May; 24(5):210-3. doi: 10.1055/s-2007-1003295" |