Retinol dehydrogenase 11 is essential for the maintenance of retinol homeostasis in liver and testis in mice.

Retinol dehydrogenase 11 (RDH11) is a microsomal short-chain dehydrogenase/reductase that recognizes all- trans - and cis -retinoids as substrates and prefers NADPH as a cofactor. Previous work has suggested that RDH11 contributes to the oxidation of 11- cis -retinol to 11- cis -retinaldehyde during the visual cycle in the eye's retinal pigment epithelium. However, the role of RDH11 in metabolism of all- trans -retinoids remains obscure. Here, we report that microsomes isolated from the testes and livers of Rdh11 -/- mice fed a regular diet exhibited a 3- and 1.7-fold lower rate of all- trans -retinaldehyde conversion to all- trans -retinol, respectively, than the microsomes of WT littermates. Testes and livers of Rdh11 -/- mice fed a vitamin A-deficient diet had ∼35% lower levels of all- trans -retinol than those of WT mice. Furthermore, the conversion of β-carotene to retinol via retinaldehyde as an intermediate appeared to be impaired in the testes of Rdh11 -/- /retinol-binding protein 4 -/- (Rbp4 -/- ) mice, which lack circulating holo RBP4 and rely on dietary supplementation with β-carotene for maintenance of their retinoid stores. Together, these results indicate that in mouse testis and liver, RDH11 functions as an all- trans -retinaldehyde reductase essential for the maintenance of physiological levels of all- trans -retinol under reduced vitamin A availability.