Fundamental studies of adrenal retinoid-X-receptor: Protein isoform, tissue expression, subcellular distribution, and ligand availability.

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), RXRß (47kDa) and RXR (56kDa). RXRγ was not detectable. After fractionation, RXRα was almost exclusively localized in the nuclear fraction. In comparison, substantial portions of RXRß 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 RXRß 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.

Levels and profiles of organochlorines and flame retardants in car and house dust from Kuwait and Pakistan: implication for human exposure via dust ingestion.

There are only few studies documenting indoor pollution in the Middle East and the Indian subcontinent. In present study, we have evaluated the occurrence of various organochlorines (OCs) and flame retardants (FRs) in dust from cars and houses of Pakistan and Kuwait. Polybrominated diphenyl ethers (PBDEs), novel brominated flame retardants (NBFRs), organophosphate FRs (PFRs), polychlorinated biphenyls (PCBs), and organochlorine pesticides (OCPs) were investigated in indoor dust from urban houses (N=15 per country) and cars (N=15 per country). PFRs were the major analytes in all four microenvironments, followed by PBDEs>NBFRs>OCPs>PCBs. For all classes of analytes, relatively lower levels were observed in car and house dust from Pakistan than Kuwait. Levels of ∑PBDEs, ∑NBFRs and ∑PFRs were higher in car dust, while ∑OCPs and ∑PCBs were higher in house dust from both countries. ∑PFRs occurred at average concentrations of 16,900, 87,900, 475, and 2500ng/g in Kuwaiti house and car, and Pakistani house and car dust, respectively. For both countries, the profiles of analytes in car dust were different from those in the house dust. Different exposure scenarios using 5th percentile, median, mean, and 95th percentile levels were estimated for adult, taxi drivers and toddlers. For Kuwaiti toddlers, assuming high dust intake and mean and 95th percentile concentrations, the values computed for ∑OCPs (1500ng/kg bw/day) were higher than RfD values, while for ∑PCBs (14.5ng/kg bw/day) it was only two-fold lower than the corresponding RfDs.