Sight and Life Magazine 1/2011

18 THE IMPORTANCE OF VITAMIN Afor the timely regulation of lung development and the relatedformation of the active metabolite RA. During embryonic development,RA regulates cell proliferation and differentiation, andregular morphogenesis. In the postnatal period, RA is important13, 14for lung growth, alveolarization, and elastin formation.“The combination of RA and EGF leadsto more than a six-fold increase of thesecretion of PGE₂”Vitamin A kinetics during fetal lung developmentLocal extrahepatic stores are present in fibroblast-like cells closeto the alveolar cells, in type II cells and in the respiratory epitheliumretinyl esters. The importance of these retinyl esters asan acute reserve during the development of the lung becomesapparent during the late phase of gestation and the beginningof lung maturation. During this period, rapid emptying of theretinyl ester stores in the lung of rat embryos occurs. 15 This depletionis the result of increased RA demand in the lung developmentprocess, because RA is instantly needed for the processof cellular differentiation and metabolic work. Indeed, RA is importantfor the formation of alveoli, and may rescue failed alveolarformation. 16,17 The effect of an adequate amount of RA onalveolar formation which starts prior to birth and lasts up to theage of eight years or even longer has recently been documented.Checkley and co-workers 18 reported that children of mothersfrom a region with vitamin A deficiency who were supplementedduring pregnancy and for six months after pregnancy with 7 mgpreformed vitamin A (7 mg retinol equivalents, RE) as a singleoral supplement once a week had significantly better lung functionat nine to 11 years old than those of mothers receiving eithera placebo or 42 mg -carotene (7 mg RE).“Vitamin A supplementation before,during and after pregnancy improvedlung function in offspring”was no further supplementation six months after delivery in thevitamin A deficient area, how might improvements of the lungfunction 10 years later be explained? One explanation might bethe sufficient repletion of vitamin A storing cells in the lung ofthe offspring, which may serve as storage sites for a longer timeperiod. Retinyl ester stores have been described in lipid-ladenfibroblasts 21 and in the bronchiolar epithelium. 22 These lipidinterstitial cells deliver RA, which induces alveolus formation. 23In the alveolus, the lipid-laden fibroblast is a major contributorto the formation of the extracellular matrix. 24 Following hydrolysisof retinyl esters to form retinol, retinol is oxidized via alcoholdehydrogenase (ADH) followed by irreversible oxidation to retinoicacid. All steps are tightly controlled via intracellular bindingproteins. Retinol bound to the cytoplasmic retinol binding protein(holo-CRBP) is protected from degradation and delivered tothe lecithin: retinol acyltransferase (LRAT) for esterification. 25Cytoplasmic retinoid binding proteins form a substrate-controllednetwork, which at least controls the delivery of RA to thenuclear-related metabolic enzymes (LRAT, ADH) via a feedbackmechanism. 26,27 This feedback network might explain why afigure 1: Decline of retinyl palmitate concentrationand in-crease of retinol in embryonic rat lungs prior to andshortly after birth (Geevarghese and Chytil) 15Retinyl palmitate (μg/g weight)12111098Birth7654321018 19 20 21 22Gestational age (days)2,50Vitamin A kinetics during lung developmentThe fact that the -carotene group had no benefit regardinglung function may be due to either poor absorption, a lowercleavage rate or polymorphism of the -carotene monooxygenase(BCMO), as discussed recently. 19,20 Administration of preformedvitamin A will contribute to a more sufficient supply ofthe lung. The effect of vitamin A on later lung function mightbe a consequence of adequate alveolar formation during fetallung development and during early childhood. However, if thereRetinol (μg/g weight)2,252,001,751,5018 19 20 21 22Gestational age (days)Birth