ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 P46

Adrenal retinoid receptors: new findings and new questions

Behling Cheng, Fatema Al-Shammari, Isra’a Ghader, Fatima Sequeira, Jitendra Thakkar & Soania Kettaneh

Biochemistry Department, Kuwait University Faculty of Medicine, Kuwait City, Kuwait.

Retinoid-X-receptor (RXR) and retinoic acid receptor (RAR) are transcription factors; each expresses in α, β and γ isoforms. Whereas RAR plays roles in growth and differentiation, RXR regulates lipids homeostasis. Specifically, RXRβ mediates intracellular control of cholesterol levels. RXR is activated by 9-cis-retinoic acid (9-cis-RA), cervonic acid, docosapentaenoic acid, adrenic acid and arachidonic acid. The present investigation was aimed to characterize adrenal retinoid receptors. Adrenals were collected from foetus (20th day of pregnancy), neonate and adult rats, and from the adult rats stimulated with ACTH (30 μg/100 g) for four consecutive days. Retinoid receptors were studied by western blotting. Cholesterol ester (CE) was determined by HPLC. Fatty acids and retinoic acids were analyzed by GC/MS and LC/MS, respectively. The results showed that development of rats from foetus/neonate to adult was accompanied by increased accumulation of CE and expression of RXRα, RXRβ and RARγ in the gland. In contrast, adrenal expression of RARα diminished. Ligand analysis revealed all-trans-retinoic acid, cervonic acid, docosapentaenoic acid, adrenic acid, and arachidonic acid; 9-cis-RA was not detectable. Based on these ligand-availabilities, RAR/RXR and RXR/RXR dimerizations could both exist in the gland; their specific isoforms in partnerships remained unknown. ACTH-stimulation resulted in altered adrenal retinoid receptor levels, but without a common pattern. Adrenal RXRβ was concentrated in the nuclear fraction, but was also found in the pellet resulted from a high speed centrifugation of the post-nuclear fraction, which could not entirely be explained as ‘contaminated’. No ACTH-induced translocation of RXRβ between nuclear and cytosolic fractions was observed. Despite new questions raised, the present data suggest a possible involvement of the retinoid receptors in regulation of rat adrenal development and steroidogenesis.

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