Growth hormone stimulates islet B-cell replication in neonatal rat pancreatic monolayer cultures

A possible role for growth hormone (GH) in stimulating islet B-cell replication was examined in neonatal rat pancreatic monolayer cultures. Addition of ovine GH (1000 ng/ml) to serum-free medium for 2 days resulted in a significant increase (+114%) in [3H]thymidine labeling of B-cells in aldehyde-thionine-stained autoradiographs, and a similar increase in the B-cell mitotic index. The stimulatory effects of GH on islet B-cell replication were greatest in serum-free medium, unaffected by glucose concentrations (2.8--16.7 mM), and not accompanied by any stimulation of insulin release. The threshold concentration of GH for a significant stimulatory effect on B-cell replication was 30 ng/ml. The insulin-like growth factor, multiplication stimulating activity (MSA), also effectively stimulated B-cell replication. Although some effects of GH are mediated by the insulin-like growth factors (IGFs), the effects of GH on B-cell replication did not appear to be mediated by IGFs since (1) the maximal effect of GH (+156%) was significantly greater than that of MSA (+91%); (2) the combination of maximal stimulatory concentrations of GH and MSA produced an additive effect; and (3) a significant effect of GH on B-cell replication was observed as early (8 h) as that produced by MSA. These results suggest that GH can stimulate islet B-cell replication directly, and that this effect may not depend on production of either insulin-like growth factors.