Specificity of cellular retinol-binding protein for compounds with vitamin A activity

Abstract

THE importance of vitamin A (retinol) for normal growth and development of vertebrates is well established¹ but its mechanism(s) of action, except in vision, remains obscure. Retinol can influence differentiation of epithelial cells² and is required for normal development of the testis and for maintenance of pregnancy³, suggesting a regulatory role resembling that of certain hormones in some aspects of its activity. The action of many steroid hormones is apparently mediated through specific cellular binding proteins⁴. We have found that rat tissues^5,6 and human⁵ and rabbit lungs⁷ contain a protein able to bind all-trans-retinol, the most potent vitamin A compound, with high affinity and specificity. In all species studied so far, this protein has the same apparent size (molecular weight 14,000, sedimenting in the 2S region on sucrose gradients) and seems to carry retinol as a non-covalently bound ligand in vivo^6,7. It has a lower molecular weight and a different fluorescence excitation spectrum⁶ than that reported for the intensively studied retinol binding protein of serum⁸, demonstrating that we are dealing with a different protein. We have purified this cellular binding protein 1,000-fold from rat testes⁶ and 600-fold from rabbit lung⁷ and report here its specificity in binding various compounds exhibiting vitamin A activity in vivo.