Developmental and tissue-specific regulation of proglucagon gene expression.

The pattern of glucagon gene expression and the posttranslational processing of proglucagon was studied in the fetal and neonatal rat. Pancreatic immunoreactive glucagon (IRG) and glucagon-like immunoreactivity (GLI) were low in both fetal pancreas and intestine, respectively. Immediately after birth, pancreatic IRG rose markedly and reached a peak concentration at postnatal day 7, followed by a gradual return to its adult level. Intestinal GLI was low until postnatal day 7 and rose steadily thereafter to adult levels. The levels of GLI in the hypothalamus were much lower than in intestine, yet the developmental accumulation of hypothalamic GLI resembled the pattern observed in intestine. In contrast, the levels of GLI and IRG in the brain stem were higher in the fetus and neonate, and decreased to adult levels. Proglucagon mRNA transcripts, uniform in size, were detected in RNA isolated from fetal or adult brainstem, pancreas, and intestine. However, fetal proglucagon mRNA transcripts were larger than adult proglucagon mRNA transcripts in pancreas and intestine, but not brainstem. The results of RNAse mapping studies, including analysis of both the 5'- and 3'-ends of the mRNA transcripts, demonstrated that the larger fetal mRNA transcripts could be accounted for by an increase in the length of the polyadenylate tail in the fetal tissues. These observations demonstrate that the developing rat exhibits tissue-specific differences in both proglucagon gene expression and the pattern of posttranslational processing of the prohormone.