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Glycogen phosphorylase: developmental expression in rat liver
C A Bloch1, M A Ozbun, S A Khan
1Department of Pediatrics, University of Colorado School of Medicine, Denver.
Insights
Fetal rats show increased hepatic glycogen phosphorylase mRNA and enzyme activity near term. Gene expression is regulated post-transcriptionally, likely via enhanced mRNA stability, ensuring adequate glucose supply for newborns.
Area of Science:
- Biochemistry
- Developmental Biology
- Molecular Endocrinology
Background:
- Fetal vulnerability to hypoglycemia due to compromised transplacental substrate supply.
- Hepatic glycogen phosphorylase is crucial for glucose homeostasis.
Purpose of the Study:
- To investigate hepatic glycogen phosphorylase gene expression during late fetal and early neonatal development in rats.
- To elucidate the regulatory mechanisms controlling glycogen phosphorylase expression in the developing liver.
Main Methods:
- Quantification of hepatic phosphorylase enzyme activity (total and phosphorylase a).
- Measurement of cellular phosphorylase mRNA concentrations using Northern blot or similar techniques.
- Assessment of transcription rates via isolated liver nuclei assays at different gestational and postnatal ages.
Main Results:
- Hepatic phosphorylase enzyme activity and mRNA levels progressively increased from 19 days of gestation until term.
- The rate of phosphorylase mRNA transcription was highest at 19 days of gestation and decreased significantly towards term.
- A discrepancy between declining transcription rates and increasing mRNA levels suggests post-transcriptional regulation.
Conclusions:
- Hepatic glycogen phosphorylase gene expression is primarily regulated post-transcriptionally in late fetal rat development.
- Increased stability of phosphorylase mRNA towards term likely contributes to the observed rise in enzyme levels.
- This regulatory mechanism ensures sufficient hepatic glycogenolytic capacity for neonatal glucose homeostasis.
Abstract:
The developing fetus is vulnerable to hypoglycemia if its transplacental substrate supply is compromised. Consequently, we examined hepatic glycogen phosphorylase gene expression in the developing rat liver by comparing the relative activities of the hepatic phosphorylase enzyme, concentrations of cellular phosphorylase mRNA, and rates of transcription in isolated liver nuclei of fetal rats at 19 days of gestation, 21 days of gestation, neonatal rats, and suckling rats. Cellular phosphorylase mRNA and enzyme activity (total and phosphorylase a) increased until term. Reciprocally, the rate of phosphorylase mRNA transcription was rapid in the rats at 19 days of gestation, and declined progressively until term. These data indicate that glycogen phosphorylase gene expression is regulated post-transcriptionally in late gestation, perhaps by an increase in phosphorylase mRNA stability towards term. This results in increased phosphorylase mRNA and enzyme expression.