Effect of estriol on the induction of progesterone receptor expression in RINm5F cells: an in vitro model for the study of gestational diabetes

Abstract

During pregnancy occur great adjustments to the maternal organism. The carbohydrate metabolism is one of the most affected aspects. Significant changes are observed in the insulin sensitivity, however, the variations of glycemia are normally slight, because of the plasticity of pancreatic ²-cells. Nevertheless, the inability of the pregnant woman's islets to respond to the increased insulin demand can result in gestational diabetes (GD). The hormones estrogen and progesterone are greatly affected during pregnancy and have their concentrations increased. Some authors suggest that these hormonal modifications could contribute to the insufficient adaptation of pancreatic ²-cells and insulin secretion. From this evidence, studies were performed by our group, and it was observed that the progesterone-induced pancreatic ²-cells death and 17-² estradiol, in combination with progesterone, raised the total of dead cells. As in other tissues, an important function of estrogen receptors is the upregulation of progesterone receptors transcription, it is possible to suggest that the estrogens, or some of its compounds, are able to regulate the progesterone receptors' expression on pancreatic cells also, leaving them more susceptible to the action of this hormone. Based on these data, the aims of this work are to determine the effect of estriol on the expression of progesterone receptors and the kinetics of cell growth in the presence of different concentrations of progesterone and estriol in insulin-secreting cells, RINm5F. The realization of this project opens perspectives for a better understanding of the pathophysiology of DG and may allow the development of strategies for both prevention and treatment of this disease.(AU)