Minireview: β-cell Replacement Therapy for Diabetes in the Twenty-First Century: Manipulation of Cell Fate by Directed Differentiation

摘要

Theorphannuclearreceptorsteroidogenicfactor1(SF-1,alsocalledAd4BP,encodedbytheNR5A1gene)isanessentialregulatorofendocrinedevelopmentandfunction.Initiallyidentifiedasatissue-specifictranscriptionalregulatorofcytochromeP450steroidhydroxylases, studies of both global and tissue-specific knockout mice have demonstrated that SF-1 is required for the develop-ment of the adrenal glands, gonads and ventromedial hypothalamus and for the proper functioning of pituitary gonadotropes.ManygenesaretranscriptionallyregulatedbySF-1,andmanyproteinsinturninteractwithSF-1andmodulateitsactivity.Whereasmice with heterozygous mutations that disrupt SF-1 function have only subtle abnormalities, humans with heterozygous SF-1mutations can present with XY sex reversal (i.e., testicular failure), ovarian failure and occasionally adrenal insufficiency; dys-regulationofSF-1hasbeenlinkedtodiseasessuchasendometriosisandadrenocorticalcarcinoma.ThecurrentstateofknowledgeofthisimportanttranscriptionfactorwillbereviewedwithaparticularemphasisonthepioneeringworkonSF-2bythelateKeithParker.