Growth hormone stimulates insulin gene expression in cultured human fetal pancreatic islets

The total body mass of the human fetus increases about 100-fold from 10-20 weeks of gestation, and peak serum GH concentrations occur at 20 weeks. Since insulin has an essential growth-promoting influence in the fetus, these experiments were designed to determine whether GH can function as a growth factor with insulin-releasing activity by stimulating insulin gene expression during embryogenesis. Pancreatic islets were isolated from human fetuses (n = 36) of 18-22 weeks gestational age. Insulin gene expression was quantified by measuring insulin mRNA by blot hybridization analysis using a [32P] cDNA probe encoding human insulin. We found that by 48 h of culture insulin gene expression was stimulated by 1.25 micrograms recombinant human GH/mL medium to 216% of the control value (n = 2). Insulin secretory capacity was expressed as a fractional stimulation ratio (FSR = F2/F1) of insulin release rates during two successive 1-h static incubations. After 48 h of culture 1.25 micrograms/mL GH stimulated the FSR value to 273% of the control value (n = 5). We conclude that recombinant human GH significantly enhances the steady state level of insulin mRNA concurrent with an increase in insulin secretory capacity, hence providing evidence for a regulatory function of GH on insulin gene expression during fetal development.