Postnatal changes in gene expression of retinal dehydrogenase and retinoid receptors in liver of rats.

Retinoic acid (RA) plays important roles in cellular differentiation and proliferation in various tissues including the liver. To explore a possible role of RA in the postnatal development of hepatic function, we analyzed RA-generation enzyme activity and the RA-related hepatic gene expressions in the suckling and weaning rats. At 5 days after birth, retinal dehydrogenase (RALDH) activity in the liver was relatively high. Its activity decreased by 70% until day 17, and then it gradually increased to a high level by the completion of weaning period. Northern blot analysis showed that RALDH2 mRNA levels decreased in the suckling period, whereas RALDH1 mRNA levels increased in the weaning period. Retinoid X receptor alpha (RXRalpha) mRNA levels increased in the suckling period and attained to a higher level at 17 days after birth. Retinoic acid receptor alpha (RARalpha) mRNA level showed only a slight and temporary increase on day 13. The mRNA levels of hepatocyte nuclear factors (HNF-4 and HNF-1alpha) exhibited parallel increases around suckling-weaning period, and the transcript levels of albumin, a typical target gene of the hepatocyte nuclear factors, increased during the suckling-weaning transition period. Electrophoretic mobility shift assay using a putative nuclear receptor-binding element on rat HNF-1 alpha gene revealed that HNF-4 homodimer, but not RXRalpha homodimer, bound to this element. These results suggest that postnatal expressions of hepatocyte-specific genes might be up-regulated by retinoid receptors, which may be related with the alterations of RALDH expression during postnatal development in the liver.