title: Fundamental studies of adrenal retinoid-X-receptor: Protein isoform, tissue expression, subcellular distribution, and ligand availability.
abstract: Adrenal gland reportedly expresses many nuclear receptors that are known to heterodimerize with retinoid-X-receptor (RXR) for functions, but the information regarding the glandular RXR is not adequate. Studies of rat adrenal homogenate by Western blotting revealed three RXR proteins: RXRα (55kDa), RXRβ (47kDa) and RXR (56kDa). RXRγ was not detectable. After fractionation, RXRα was almost exclusively localized in the nuclear fraction. In comparison, substantial portions of RXRβ and RXR were found in both nuclear and post-nuclear particle fractions, suggesting genomic and non-genomic functions. Cells immunostained for RXRα were primarily localized in zona fasciculata (ZF) and medulla, although some stained cells were found in zona glomerulosa (ZG) and zona reticularis (ZR). In contrast, cells immunostained for RXRβ were concentrated principally in ZG, although some stained cells were seen in ZR, ZF, and medulla (in descending order, qualitatively). Analysis of adrenal lipid extracts by LC/MS did not detect 9-cis-retinoic acid (a potent RXR-ligand) but identified all-trans retinoic acid. Since C20 and C22 polyunsaturated fatty acids (PUFAs) can also activate RXR, subcellular availabilities of unesterified fatty acids were investigated by GC/MS. As results, arachidonic acid (C20:4), adrenic acid (C22:4), docosapentaenoic acid (C22:5), and cervonic acid (C22:6) were detected in the lipids extracted from each subcellular fraction. Thus, the RXR-agonizing PUFAs are available in all the main subcellular compartments considerably. The present findings not only shed light on the adrenal network of RXRs but also provide baseline information for further investigations of RXR heterodimers in the regulation of adrenal steroidogenesis.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Kuwait University Health Science Center, P. O. Box 24923, Safat 13110, Kuwait. Electronic address: behling@hsc.edu.kw.
authors.forename: Behling
authors.initials: B
authors.lastname: Cheng
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Kuwait University Health Science Center, P. O. Box 24923, Safat 13110, Kuwait.
authors.forename: Fatema H
authors.initials: FH
authors.lastname: Al-Shammari
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Kuwait University Health Science Center, P. O. Box 24923, Safat 13110, Kuwait.
authors.forename: Isra'a A
authors.initials: IA
authors.lastname: Ghader
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Kuwait University Health Science Center, P. O. Box 24923, Safat 13110, Kuwait.
authors.forename: Fatima
authors.initials: F
authors.lastname: Sequeira
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Kuwait University Health Science Center, P. O. Box 24923, Safat 13110, Kuwait.
authors.forename: Jitendra
authors.initials: J
authors.lastname: Thakkar
authors.affiliation: Department of Medical Laboratory Science, Faculty of Allied Health, Kuwait University Health Science Center, P.O. Box 31470, Sulaibekhat 90805, Kuwait.
authors.forename: Thazhumpal C
authors.initials: TC
authors.lastname: Mathew
mesh_terms: D000302:Adrenal Cortex / Q000166:cytology / Q000378:metabolism; D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism*; D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D009928:Organ Specificity; D054730:Protein Interaction Domains and Motifs; D020033:Protein Isoforms / Q000819:agonists / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport; D017208:Rats, Wistar; D047490:Retinoid X Receptor alpha / Q000819:agonists / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D049230:Retinoid X Receptor beta / Q000819:agonists / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism*; D015383:Zona Fasciculata / Q000166:cytology / Q000378:metabolism; D015385:Zona Reticularis / Q000166:cytology / Q000378:metabolism
chemical_list: D015415:Biomarkers; D005231:Fatty Acids, Unsaturated; D008024:Ligands; D020033:Protein Isoforms; D047490:Retinoid X Receptor alpha; D049230:Retinoid X Receptor beta; D014212:Tretinoin
keywords: Adrenal cortex; Polyunsaturated fatty acid; Retinoic acid; Retinoid-X-receptor; Steroidogenesis