EXPRESSION OF THE HEPATIC INSULIN-RECEPTOR GENE IN THE RAT DURING POSTNATAL-DEVELOPMENT

Changes in the expression of the liver insulin receptor are known to o ccur in the rat during postnatal development. To assess whether such c hanges occur at the level of gene expression, steady-state levels of i nsulin receptor mRNA and transcription rates of the receptor gene have been measured in livers of rats from birth (1 day) to adulthood (60 d ays). Northern blot analysis of liver RNA revealed two major insulin r eceptor mRNA species of 9.5 and 7.5 kb. When normalized to beta actin mRNA, insulin receptor mRNA levels increased 4-fold between 1 and 15 d ays, remained stable between 15 and 30 days, and decreased 2-fold betw een 30 and 60 days. These changes were fully suppressed by in vivo tre atment with actinomycin D, an inhibitor of gene transcription. In vitr o nuclear transcription assays showed that the rate of transcription o f the insulin receptor gene increased 2-fold between 1 and 30 days, In sulin receptor concentration in liver membrane fractions did not exact ly parallel insulin receptor mRNA levels since it increased by 20-30% from 1 to 10 days and decreased 2-fold from 10 to 60 days. During the suckling-weaning transition, insulin receptor mRNA level decreased 2-f old in rats weaned onto a high carbohydrate diet but remained unchange d in rats weaned onto a high fat diet. Throughout postnatal life, an i nverse relationship was observed between liver insulin receptor mRNA a nd plasma insulin levels. These results show that transcriptional chan ges in insulin receptor gene expression occur postnatally and suggest that such changes may be insulin-related.