Adaptation of pancreatic islet B-cells during the last third of pregnancy:regulation of B-cell function and proliferation by lactogenic hormones in rats

In rodents, placental lactogen (PL)-I is considered to be the first trigger to enhance pancreatic islet B-cell function, and after its secretion is di minished at mid-pregnancy, PL-II takes over this role, However little infor mation is available on the regulation of islet B-cell function and prolifer ation by lactogenic hormones during the last third of pregnancy This was th e focus of the present study using rats in which pregnancy was forcibly pro longed. This rat possesses unique characteristics in that PL-I is re-secret ed during the prolonged period of pregnancy and the peak concentrations in maternal circulation are comparable with those observed during mid-pregnanc y in normal-pregnancy rats. Pregnancy was prolonged by successive administr ation of pregnant mare's serum gonadotropin (30IU/rat, s.c. on day 12) and human chorionic gonadotropin (10 IU/rat, i.v. on day 14), When the insulin secretory responses to 10 mmol/l glucose in islets obtained from normal-pre gnancy and prolonged-pregnancy rats were tested, each insulin secretory res ponse correlated well with the values of plasma lactogenic activity through out the period of pregnancy and lactation. Examination of B-cell proliferat ion in normal-pregnancy rats showed that 5-bromo-2'-deoxyuridine (BrdU) inc orporation into dividing B-cells reached a maximum on day 15 and then decre ased markedly towards term. No increase in B-cell proliferation was observe d on day 19 when plasma lactogenic activity reached the maximum. In prolong ed-pregnancy rats, BrdU incorporation also continued to decrease as observe d in normal-pregnancy rats after day 15, and then no enhancement in B-cell proliferation was observed even when the plasma lactogenic activity, includ ing re-secreted PL-I, reached maximum. These results suggest that, in the l ast third of pregnancy, B-cell proliferation is no longer stimulated by lac togenic hormones in contrast to the insulin secretory response which is sus tained.