Rapid, nongenomic estrogen actions protect pancreatic islet survival.
The gonadal steroid, 17beta-estradiol (E(2)), acts as a protective hormone preventing beta-cell apoptosis in vivo in mice of both sexes and in cultured mouse and human islets. E(2) signals via the classical estrogen receptor (ER)alpha and ERbeta, an extranuclear form of ERalpha and the G protein-coupled estrogen receptor (GPER). In a recent study, we determined the contribution of these receptors to beta-cell survival, using a combination of genetic and pharmacological tools in mice and cultured mouse and human islets. We showed that E(2) favors islet survival by preventing apoptosis via ERalpha and ERbeta through ERE-independent, extra-nuclear mechanisms and with a predominant ERalpha effect. We also revealed that E(2) prevents apoptosis via GPER-dependent mechanisms. Here, we show that E(2) prevents apoptosis independently of gene transcription or de novo protein synthesis suggesting that E(2) cytoprotection happens independently of nuclear events. Furthermore, we report that E(2) islet cytoprotection can be mimicked by the nonfeminizing E(2) stereoisomer, 17alpha-estradiol, suggesting that it is partially non-estrogen receptor mediated. These studies identify novel estrogen pathways and targets to protect islet survival.
Liu
Suhuan
S
Department of Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL 60611, USA.
Mauvais-Jarvis
Franck
F
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects*; D004958:Estradiol / Q000494:pharmacology*; D047628:Estrogen Receptor alpha / Q000502:physiology; D047629:Estrogen Receptor beta / Q000502:physiology; D005260:Female; D006801:Humans; D007515:Islets of Langerhans / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D013997:Time Factors
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004958:Estradiol