CONICET | Buscador de Institutos y Recursos Humanos

It has been previously described that transgenic female mice overexpressing b subunit of human chorionic gonadotropin (hCGb+), exhibited elevated levels of hCG, developed hyperprolactinemia, infertility and obesity with presence of abdominal fat at adulthood. These transgenic females presented with alterations on glucidic and lipidic metabolism, with elevated basal insulinemia and serum triglycerides. The aim of this study was to analyze the influence of hyperprolactinemia on the metabolic disturbances described in this model. To this end, the dopamine agonist, cabergoline (500 µg/kg; vía i.p.) was administrated to 5-week-old transgenic female mice every other day during a week (hCGb+cab). At 6 month of age intraperitoneal glucose tolerance test (IGTT) and Intraperitoneal insulin tolerance test (ITT) were performed in mice fasted for 6 and 4 hr respectively. With respect to IGTT 2 g/kg of glucose were injected (i.p.), whereas 0,75 UI/kg of insulin (i.p.) were injected for ITT; then, serum glucose levels were determined at 0, 30, 60 and 90 minutes post-injection. Cabergoline treatment produce a partial recovery of IGTT and a full prevention of insulin resistance on transgenic females (p<0,001). Besides, a significant decrease in serum insulin and triglycerides levels in hCGb+cab respect to control hCGb+ females was observed. On the other hand, pancreatic genic expression of preproinsulin (Ins-1, Ins-2) and glucagon (Gcg) was analyze by quantitative Real Time PCR. hCGb+cab females presented with a significant decrease in Ins-1 e Ins-2 gene expression levels in comparison to hCGb+ females (p<0,05), and no changes in expression levels of Gcg were observed. In conclusion, cabergoline treatment was able to reverse metabolic disturbances observed in transgenic females hypersecreting hCG, thus demonstrating a key role of hyperprolactinemia on the transgenic phenotype.