Persistence of peptidylglycine alpha-amidating monooxygenase activity and elevated thyrotropin-releasing hormone concentrations in fetal rat islets in culture

Abstract

Two experimental systems were used to investigate the relationship between TRH content and peptidylglycine alpha-amidating monooxygenase (PAMase) activity of the neonatal rat pancreatic islets: freshly isolated islets from rats aged 1-14 days, and fetal islets maintained in culture for 3 weeks. TRH was present in freshly isolated islets and in newly formed fetal islets in culture. However, while the TRH concentration in freshly isolated islets measured by RIA followed the same ontogenic pattern as that in the total pancreas, peaking during the first week of life (78 pg/micrograms DNA on day 4) and decreasing thereafter to reach 4 pg/micrograms DNA on day 14, the TRH content of fetal islets in culture did not decrease with time (65 pg/micrograms DNA on day 1 and 80 pg/micrograms DNA after 3 weeks in culture). Similarly, using immunocytochemistry, immunoreactive cells were only seen at day 2 in freshly isolated islets. In contrast, in fetal islets, TRH cells were present throughout the culture period. In both experimental systems, TRH was localized in beta-cells. PAMase activity paralleled TRH concentration, peaking during the first week of life in freshly isolated islets and remaining unchanged in the fetal islets in culture. PAMase activity is, therefore, present in the endocrine pancreas. The results suggest that PAMase activity is a rate-limiting step in TRH biosynthesis in this tissue.