Hormonal regulation of hepatic P-enolpyruvate carboxykinase (GTP) during development

Abstract

Hepatic gluconeogenesis in the rat does not begin until birth. The enzyme P-enolpyruvate carboxykinase appears initially at birth and is the final enzyme in the gluconeogenic sequence to develop. The appearance of this enzyme in the cytosol of rat liver is caused by the stimulation of enzyme synthesis, probably due directly to an increase in the hepatic concentration of cAMP. Enzyme degradation does not begin until 36 hours after birth. Studies with fetal rats in utero have shown that dibutyryl cAMP or glucagon will stimulate P-enolpyruvate carboxykinase synthesis and that this effect can be blocked by insulin. Insulin is known to depress the synthesis of P-enolpyruvate carboxykinase in adult rat liver and in Reuber H-35 liver cells in culture. The glucocorticoids are without effect on the synthesis of the enzyme in fetal rat liver. Work by Girard et al. (J. Clin. Invest. 52: 3190, 1973) has established that the molar ratio of insulin to glucagon drops from 10 immediately after birth, to 1 after one hour. This is due to both a rise in glucagon and a fall in insulin concentrations at birth. These studies, together with our work on the synthesis of P-enolpyruvate carboxykinase, indicate that the sharp drop in the concentration of insulin may relieve the normal inhibition of enzyme synthesis. This would allow the initial stimulation of enzyme synthesis by the glucagon-mediated rise in the concentration of cAMP.—Hanson, R. W., L. Reshef and J. Ballard. Hormonal regulation of hepatic P-enolpyruvate carboxykinase (GTP) during development. Federation Proc. 34: 166–171, 1975.

From Session VI, Development and Aging at the Molecular Level, of the FASEB Conference on Biology of Development and Aging, presented at the 58th Annual Meeting of the Federation of American Societies for Experimental Biology, Atlantic City, N.J., April 11, 1974.

This work was supported in part by grants AM-11279, HD-05874, CA-10916 and AM-16009 from the National Institutes of Health.

Recipient of a Career Development Award, K4-AM-15365 from the Public Health Service.