Editorial: Molecular Endocrinology articles in the spotlight for November 2012.

Welcome to the November issue of Molecular Endocrinology. I am pleased to report that beginning with this issue, the editors will identify a single article each month to be made freely available upon publication. In addition, all minireviews will be freely available immediately upon publication effective with this issue. Our first freely available article is by Mao et al., “Circadian Gating of Epithelial-to-Mesenchymal Transition in Breast Cancer Cells via Melatonin-Regulation of GSK3 .” In this study, the authors investigated the connection between circadian/melatonin disruption and breast cancer risk in shift workers. Their studies used a unique xenograft model with human breast cancer cells maintained in nude rats. Disruption of nighttime melatonin production by exposure of the host to light at night has far-reaching biological consequences, including disruption and activation of key proliferative/survival pathways in the xenograft human breast cancer cells including MAPK/ERK and PI3K/AKT, which repress glycogen synthase kinase 3 (GSK3 ) activity and drive epithelial-tomesenchymal transition. Thus, this study identifies a molecular mechanism that could contribute to the increased risk of breast cancer incidence in industrialized nations characterized by excessive use of artificial light during the night. “20-HETE Induces Hyperglycemia through the cAMP/PKA-PhK-GP Pathway” by Lai et al. demonstrated that hyperglycemia and hypertension in CYP4F2 transgenic mice were ameliorated with HET0016 [a selective 20-hydroxyeicosatetraenoic acid (20-HETE) inhibitor] treatment. Furthermore, 20-HETE was shown to activate glycogen phosphorylase, which is a target for diabetes therapy. Therefore, through induction of glycogenolysis through the cAMP/protein kinase A-phosphorylase kinase-glycogen phosphorylase pathway, 20HETE could participate in the common pathogenesis of hypertension and hyperglycemia. This study implicates 20-HETE as a potential new target for hypertension and hyperglycemia therapy. Williams et al.’s “The microRNA (miR)-199a/214 Cluster Mediates Opposing Effects of Progesterone and Estrogen on Uterine Contractility during Pregnancy and Labor” investigates the role of the clustered miRNAs, miR-199a-3p and miR-214, as important mediators of the opposing action of progesterone (P4) vs. estradiol-17 (E2) on myometrial quiescence and contractility during pregnancy and labor. Specifically, P4 and E2 exert opposite effects on these clustered miRs with P4 triggering induction and E2 repression via differential effects on the zinc finger, E-box binding homeobox protein (ZEB1). Furthermore, miR199a-3p and miR-214 act to block TNF-induced myometrial contractility via an inhibition of cyclooxygenase-2, an enzyme that catalyzes the formation of proinflammatory cytokines. Their findings in mice and humans provide new insight into strategies to prevent preterm birth as specific targets are identified that respond differentially to endogenous steroid hormones during normal labor. These studies and others in this issue highlight the impact of endocrinology research in both prevention and treatment of many conditions. Congratulations to these researchers, as well as those who produced all of the excellent science in this issue, on broadening our knowledge in such diverse areas. We also hope you enjoy the new freely available articles that will hereafter be a monthly feature in Molecular Endocrinology. Donald B. DeFranco, Ph.D. Editor-in-Chief, Molecular Endocrinology