Role of prolactin versus growth hormone on islet B-cell proliferation in vitro: Implications for pregnancy

This study investigated the effects of homologous rat PRL (rPRL) and rat GH (rGH) on islet growth as indicated by modifications in insulin secretion, islet cell proliferation, and islet volume with neonatal and adult rat islets in vitro. The number of proliferating cells was determined by immunocytochemical staining for 5-bromo-2′-deoxyuridine (BrdU) incorporated into replicating DNA during the final 24 h of culture. When neonatal rat islets were examined by laser scanning confocal microscopy, more than 90% of the BrdU-labeled nuclei were observed in B-cells with insulin immunoreactitivity. In neonatal rat islets, rPRL was much more effective than rGH in increasing insulin secretion (3.7-fold vs. 1.4-fold) during the 10 days of culture. The number of BrdU-labeled nuclei per islet was increased from 2.9 ± 0.4 (n = 77) in control islets to 47.3 ± 2.7 (n = 95) with rPRL (16.3-fold) and 9.7 ± 0.8 (n = 84) with rGH (3.3-fold). The effects of rPRL and rGH on both insulin secretion and BrdU labeling were approximately additive. After 10 days, an increased average islet volume was only observed with rPRL. When followed for 36 days, the total amount of islet tissue was unchanged for control islets (1.1-fold), more than doubled with rPRL (2.5-fold), and only slightly increased with rGH (1.4-fold). From the observed rates of islet cell proliferation and increases in islet volumes, doubling times of 23-24 days for rPRL and 89-91 days for rGH can be estimated. Of other proposed islet growth factors, cholecystokinin, epidermal growth factor, platelet-derived growth factor, and 2-aminoisobutyric acid, an increase in insulin secretion and islet cell proliferation was only observed with cholecystokinin in neonatal rat islets. However, both effects were less than 20% of those observed with rPRL. In adult rat islets, rPRL was also more effective than rGH in increasing insulin secretion (1.6-fold vs. 1.2-fold) during the 9 days of culture. The number of BrdU-labeled nuclei per islet was increased from 2.7 ± 0.5 (n = 96) in control islets to 9.5 ± 0.6 (n = 175) with rPRL (3.5-fold). In contrast to the neonatal islets, rGH had no effect on the number of BrdU-labeled nuclei per islet in adult rat islets (2.4 ± 0.3, n = 194). This study demonstrates that rPRL and rGH have direct effects on the growth of neonatal and adult rat islets in vitro. However, for all parameters examined the effects of rPRL were much larger than those observed with rGH. This suggests that lactogenic, rather than sommatotropic, activity is a potent regulator of islet function and supports our hypothesis that lactogens, either as PRL or placental lactogen, are regulators of islet function during pregnancy.