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      Vitamin A, endocrine tissues and hormones: interplay and interactions

      review-article
      1 , 2 , 3 , 1 , 3 , 1 , 2 , 3 ,
      Endocrine Connections
      Bioscientifica Ltd
      vitamin A, retinol, hormones

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          Abstract

          Vitamin A (retinol) is a micronutrient critical for cell proliferation and differentiation. In adults, vitamin A and metabolites such as retinoic acid (RA) play major roles in vision, immune and brain functions and tissue remodelling and metabolism. This review presents the physiological interactions of retinoids and endocrine tissues and hormonal systems. Two endocrine systems have been particularly studied. In the pituitary, retinoids target the corticotrophs with a possible therapeutic use in corticotropinomas. In the thyroid, retinoids interfere with iodine metabolism and vitamin A deficiency aggravates thyroid dysfunction caused by iodine-deficient diets. Retinoids use in thyroid cancer appears less promising than expected. Recent and still controversial studies investigated the relations between retinoids and metabolic syndrome. Indeed, retinoids contribute to pancreatic development and modify fat and glucose metabolism. However, more detailed studies are needed before planning any therapeutic use. Finally, retinoids probably play more minor roles in adrenal and gonads development and function apart from their major effects on spermatogenesis.

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          Most cited references94

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          A transcriptional co-repressor that interacts with nuclear hormone receptors.

          Transcriptional silencing mediated by nuclear receptors is important in development, differentiation and oncogenesis. The mechanism underlying this effect is unknown but is one key to understanding the molecular basis of hormone action. Here we identify a receptor-interacting factor, SMRT, as a silencing mediator (co-repressor) for retinoid and thyroid-hormone receptors. SMRT is a previously undiscovered protein whose association with receptors both in solution and bound to DNA-response elements is destabilized by ligand. The interaction with mutant receptors correlates with their transcriptional silencing activities. In vivo, SMRT functions as a potent co-repressor, and a GAL4 DNA-binding domain fusion of SMRT behaves as a frank repressor of a GAL4-dependent reporter. Together, our results identify a new class of cofactors which may be important mediators of hormone action.
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            A membrane receptor for retinol binding protein mediates cellular uptake of vitamin A.

            Vitamin A has diverse biological functions. It is transported in the blood as a complex with retinol binding protein (RBP), but the molecular mechanism by which vitamin A is absorbed by cells from the vitamin A-RBP complex is not clearly understood. We identified in bovine retinal pigment epithelium cells STRA6, a multitransmembrane domain protein, as a specific membrane receptor for RBP. STRA6 binds to RBP with high affinity and has robust vitamin A uptake activity from the vitamin A-RBP complex. It is widely expressed in embryonic development and in adult organ systems. The RBP receptor represents a major physiological mediator of cellular vitamin A uptake.
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              Retinoids, retinoic acid receptors, and cancer.

              Retinoids (i.e., vitamin A, all-trans retinoic acid, and related signaling molecules) induce the differentiation of various types of stem cells. Nuclear retinoic acid receptors mediate most but not all of the effects of retinoids. Retinoid signaling is often compromised early in carcinogenesis, which suggests that a reduction in retinoid signaling may be required for tumor development. Retinoids interact with other signaling pathways, including estrogen signaling in breast cancer. Retinoids are used to treat cancer, in part because of their ability to induce differentiation and arrest proliferation. Delivery of retinoids to patients is challenging because of the rapid metabolism of some retinoids and because epigenetic changes can render cells retinoid resistant. Successful cancer therapy with retinoids is likely to require combination therapy with drugs that regulate the epigenome, such as DNA methyltransferase and histone deacetylase inhibitors, as well as classical chemotherapeutic agents. Thus, retinoid research benefits both cancer prevention and cancer treatment.

                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                October 2017
                18 July 2017
                : 6
                : 7
                : R121-R130
                Affiliations
                [1 ]Université de Bordeaux Nutrition et Neurobiologie Intégrée, Bordeaux, France
                [2 ]Department of Nuclear Medicine CHU de Bordeaux, Pessac, France
                [3 ]INRA Nutrition et Neurobiologie Intégrée, UMR1286, Bordeaux, France
                Author notes
                Correspondence should be addressed to J B Corcuff; Email: jean-benoit.corcuff@ 123456chu-bordeaux.fr
                Article
                EC170101
                10.1530/EC-17-0101
                5551430
                28720593
                41348033-f65d-49a5-b06d-48e7c3ede127
                © 2017 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

                History
                : 3 July 2017
                : 18 July 2017
                Categories
                Review

                vitamin a,retinol,hormones
                vitamin a, retinol, hormones

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