Effect of 17 beta-estradiol on the expression of progesterone receptors in RINm5F pancreatic beta cells

Abstract

During the pregnancy it takes place some metabolic adjustments that enable fetal development and maintenance of maternal homeostasis. Despite of these adjustments, a number of women can develop gestational diabetes (GD), a condition that results of the poor adaptation of pancreatic islets to the increased insulin demand. Recently, it has been suggested that progesterone, whose high concentrations at the second trimester of pregnancy overlaps with GD onset, could contribute to the insufficient adaptation of insulin secretion. In contrast, other researchers showed that estradiol possess an antidiabetic function. Beginning from theses evidences, we established in our laboratory an in vitro model to study the effects of progesterone and estradiol on pancreatic ² cell death. Results showed that progesterone induces apoptotic death of these cells and that estradiol potentiated the progesterone effect. Since previous works have reported that female rats exhibit low levels of progesterone receptors (Pgr) when subjected to knockout of the ER± receptor, we suggested that the estradiol could be involved in the regulation of the expression of Pgr in ² cells, contributing to their susceptible to progesterone effects. So, the objective of this study is to verify the effect of 17²-estradiol in inducing the expression of Pgr in pancreatic cells. For this purpose, RINm5F cells will be used. Cells will be treated with progesterone and 17²-estradiol in different concentrations (0.2 to 100 µM) and periods of incubation (24 and 48h). The expression of progesterone receptors will be evaluated by real time PCR.(AU)