Vitamin A, endocrine tissues and hormones: interplay and interactions

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 targets 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.

Figure 1

Retinol bound in the plasma to retinol-binding protein (RBP) and transthyretin is uptaken by an RBP-binding transporter, STRA6. Retinyl esters enter the cells associated with chylomicrons (4) to be transformed into retinol by retinyl ester hydrolase. This step can be reversed by lecithin:retinol acyltransferase (2). All-trans retinol is metabolised by retinol dehydrogenases (3) into all-trans retinaldehyde. This step can be reversed by retinal reductase (4). All-trans retinaldehyde is metabolised into all-trans retinoic acid (atRA) by retinaldehyde dehydrogenase (5). atRA is degraded by oxidation/catabolised by cytochrome P450 enzymes (mainly CYP26A1) (6). atRA actions are mediated primarily by RA receptors via heterodimers of retinoic acid receptor (RAR) and retinoic X receptors (RXR) acting with cofactors (CoF) on RA response elements (RAREs) of target genes. In the absence of retinoid ligand, RAR/RXR heterodimers are bound to transcriptional repressors. Upon retinoid ligand binding, the heterodimers are bound to coactivator proteins. atRA may also exert non-genomic effects through cytoplasmic kinases (20, 22).