Submit Manuscript | http://medcraveonline.com Abbreviations: Ct, crossing threshold; E, estriol; ETD, estradiol; GD, gestational diabetes, GC, gene of control; GI, gene of interest; HPRT, phosphoribosyltransferase; PBS, phosphate-buffered saline; PI, propidium iodide; PG, progesterone; PR, progesterone receptor; PGRMC1, progesterone receptor membrane component 1; PRA, progesterone receptor isoform A; PRB, progesterone receptor isoform B; TNF- a, tumor necrosis factor alpha Introduction Among the complications in pregnancy, gestational diabetes (GD) is one of the most common, affecting about 3-7% of pregnant women. 1 GD is a condition characterized by intolerance to carbohydrates resulting in hyperglycemia, which may persist after delivery. 2 According to the study of Hyperglycemia and Adverse Pregnancy Outcome 3 and the International Diabetes Federation, 4 pregnant women with GD, when untreated, have increased risk of premature rupture of membranes and preterm delivery. The fetus, on the other hand, has an increased chance to develop respiratory distress syndrome, cardiomyopathy, polycythemia, hypocalcemia and hypomagnesemia, hypoglycemia and macrosomia. The GD pathophysiology is still unknown, but many studies have focused on the understanding of the action of specifc hormones in pregnancy and its relationship to changes in carbohydrate metabolism during this period. 5,6 Regardless, it has been shown that progesterone, whose high levels in the second trimester overlaps with GD onset, could contribute to insuffcient insulin secretion to the increased demands of pregnancy. 1 High progesterone levels have been also correlated with the development of glucose abnormalities in pregnancy and progesterone receptor-knockout mice are found to have improved glucose tolerance. 7 Accordingly, Rebarber et al., 8 studied the incidence of GD among pregnant women who have received weekly doses of 250 mg progesterone intramuscularly for preterm delivery prevention. The results showed that the incidence of DG was higher inwomen who received progesterone (12.9%) compared to the control group (4.9%). Many studies, in contrast, have suggested a possible antidiabetic effect of estrogens. Le May et al., 9 demonstrated that estradiol, through the binding to ERα receptor, protected β-cells from apoptosis induced by oxidative damage. Another report showed that mice treated with estradiol showed β-cell hypertrophy, preventing diabetes development. 10 The molecular mechanism involved in the progesterone action in DG scenario has not yet been clarifed, however we have shown that progesterone is able to induce pancreatic β-cell death by an oxidative stress-dependent mechanism. 11 Although estradiol and estriol have been related to cell protection from oxidative stress induced apoptosis, these hormones potentiated progesterone effect on β-cell death when used in pharmacological concentrations, even though they were proved to be much less toxic than progesterone. Endocrinol Metab Int J. 2018;6(2):142‒147. 142 © 2018 Borcari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and build upon your work non-commercially. Estrogens modulate progesterone receptor expression and may contribute to progesterone- mediated apoptotic β-cell death Volume 6 Issue 2 - 2018 Nathalia Ruder Borcari, 1 Jeniffer Farias dos Santos, 1 Sarah Ingrid Farias dos Santos, 1 Felipe Santiago Chambergo Alcalde, 1 Anna Karenina Azevedo-Martins, 1 Viviane Abreu Nunes 1 1 School of Arts, Sciences and Humanities, Brazil 2 Federal University of Juiz de Fora, Brazil Correspondence: Viviane Abreu Nunes, School of Arts, Sciences and Humanities of University of Sao Paulo, Av. Arlindo Bettio, 1000, Ermelino Matarazzo, CEP 03170-050, Sao Paulo, SP, Brazil, Tel +55 (11) 3091-8828, Email vanunes@ib.usp.br Received: November 10, 2017 | Published: April 10, 2018 Abstract InThe use of progesterone to prevent preterm delivery has been related to the increased risk of gestational diabetes (GD) development. We have shown previously that PG is able to trigger β-cells death and estrogens potentiated this progesterone effect. Since the expression of progesterone receptors (PR) is under control of estrogens in some tissues, we hypothesized that these hormones could regulate PR expression in pancreatic β-cells. The aim of this work was to evaluate the effect of estriol and estradiol on the regulation of the PRB (a physiologically active cytosolic receptor) and of PGRMC1 (the membrane component 1) expression in insulin-producing RINm5F cells. Cells were treated with the steroids hormones (estriol and 17b-estradiol) in pregnancy physiological or pharmacological concentrations for 6 or 24 h. RNA were extracted by TRIzol® method. Gene expression was analyzed by quantitative PCR using specific primers for PRB and PGRMC1. Treatment of cells with estriol or estradiol by 6 h slightly affected PGRMC1 expression. In contrast, 0.1, 1.0 and 10 μM estriol treatment for 6 h increased PRB expression by 15, 28 and 8-fold, respectively in comparison to untreated cells. Expression of PR was less affected after incubation of RINm5F cells for 24 h with the estrogens. These results confirmed that estrogens can regulate the expression of PR also in pancreatic cells, which may represent a mechanism to modulate progesterone action in these cells. The presented data may contribute to the better understanding of the interaction between steroid hormones and insulin producing cells, opening perspectives to the future treatment and therapeutic strategies for the GD management. Keywords: progesterone, estrogens, progesterone receptors, b-cells, gestational diabetes Endocrinology & Metabolism International Journal Research Article Open Access