Effects of vitamin A deficiency and retinoic acid treatment on expression of a phosphoenolpyruvate carboxykinase-bovine growth hormone gene in transgenic mice.

Vitamin A regulation of specific promoter domains of the phosphoenolpyruvate carboxykinase (PEPCK) gene was tested in a PEPCK/bovine growth hormone (bGH) transgenic mouse model. Vitamin A deficiency causes a significant decrease in hepatic bGH mRNA when expression is driven by either a 533-base-pair (bp) PEPCK promoter fragment (from position -460 to +73) or a 428-bp PEPCK promoter fragment (from position -355 to +73). Treatment of vitamin A deficient transgenic mice with all-trans retinoic acid (RA) increases bGH mRNA levels above those measured with the deficiency. Hepatic retinoic acid receptor (RAR)beta mRNA levels also change with vitamin A deficiency and supplementation, but not RAR alpha mRNA levels. These results indicate that all-trans RA plays a physiologic role in regulating expression of a gluconeogenic gene in liver.