N-(4-HYDROXYPHENYL)RETINAMIDE (FENRETINIDE) AND NEPHRECTOMY ALTER NORMAL PLASMA RETINOL-BINDING PROTEIN-METABOLISM

We have reported previously that injecting vitamin A-deficient rats wi th N-(4-hydroxyphenyl)retinamide causes a significant reduction in the liver retinol-binding protein concentration and a 2 fold rise in the kidney retinol-binding protein concentration. This presumably reflects a rapid translocation of retinol-binding protein from the liver to th e kidney through the plasma, although no rise in plasma retinol-bindin g protein is detected. In the present studies, nephrectomized rats wer e used to determine if retinol-binding protein accumulating in kidneys passes through the plasma. Bilateral nephrectomy in control rats caus ed the plasma retinol-binding protein concentration to approximately d ouble by 5 hr postsurgery. However, nephrectomy plus N-(4-hydroxypheny l)retinamide treatment did not result in an increase in the plasma ret inol-binding protein concentration. Therefore, the lowering of liver r etinol-binding protein concentration in response to N-(4-hydroxyphenyl )retinamide treatment was not accounted for by an accumulation of reti nol-binding protein in the plasma compartment. Interestingly, the musc le retinol-binding protein concentration increased with nephrectomy pl us N-(4-hydroxyphenyl)retinamide treatment. The ratio of muscle retino l-binding protein plasma retinol-binding protein in vitamin A-deficien t nephrectomized rats treated with N-(4-hydroxyphenyl)retinamide was s ignificantly higher than in comparable rats treated with either carrie r or retinol. We conclude that in vivo N-(4-hydroxyphenyl)retinamide i nduces the secretion of retinol-binding protein from the liver. Since the N-(4-hydroxyphenyl)retinamide-retinol-binding protein complex does not bind with transthyretin it rapidly leaves the plasma. In non-neph rectomized rats this complex is rapidly filtered by the kidney. Nephre ctomizing rats causes the retinol-binding protein secreted in response to N-(4-hydroxyphenyl)retinamide to diffuse into interstitial fluid