Effects of pregnancy hormones on pancreatic islets in organ culture.

Pregnancy is associated with hyperinsulinaemia and decreased glucose tolerance which may lead to gestational diabetes. Sera from pregnant women in the last trimester were found to stimulate insulin secretion of mouse pancreatic islets maintained in organ culture suggesting a direct effect of pregnancy hormones and/or metabolites on the endocrine pancreas. Previous studies have shown that progesterone and human placental lactogen (hPL) had direct effects on isolated islets and in the present study the effects of combined addition of these hormones to the cultured islets were evaluated. hPL, 1 microgram/ml was found to prevent the decrease in the islet insulin content due to progesterone 100 ng/ml, and hPL induced an increase in the DNA-content compared with the progesterone treated islets. The effect of the hormones on the DNA synthesis was evaluated by incorporation of [3H]thymidine into newborn rat islets. Progesterone in a high concentration, 1 microgram/ml, inhibited while 0.1 and 1 microgram/ml hPL stimulated the [3H]thymidine incorporation. These results indicate that progesterone may contribute to the increased glucose-induced insulin release during pregnancy and hPL to the beta-cell hyperplasia. Since progesterone and hPL counteracted each other with regard to both insulin content and DNA-synthesis in the islets, the direct interaction between these two hormones on the beta-cell may be of importance for the changes in glucose metabolism during pregnancy.