Editorial: Molecular Endocrinology Articles in the Spotlight for May 2012

This month’s issue of Molecular Endocrinology features many excellent articles. We have picked some of the most compelling new research to spotlight: In “Mutations in MCT8 in Patients With AllanHerndon-Dudley-Syndrome Affecting Its Cellular Distribution,” Kersseboom et al (freely available at http://mend.endojournals.org/) observes cell-type dependent effects of mutations within the monocarboxylate transporter 8 (MCT8) thyroid hormone transporter, suggesting tissue-specific effects on thyroid hormone transport in patients with MCT8 mutations. Patients with Allan-Herndon-Dudley-syndrome exhibit severe psychomotor retardation illustrating the importance of MCT8 in maintaining thyroid hormone homeostasis in the brain, particularly during development. The authors identify 2 distinct cellular pathogenic mechanisms of MCT8 mutations: some mutations result in partial or complete loss of thyroid hormone transport activity without affecting cellular MCT8 protein distribution, whereas other mutations mainly disturb protein expression and trafficking. The severity of the phenotype of patients with MCT8 mutations is independent of the underlying pathogenic mechanism, suggesting that even minor perturbations in thyroid hormone transport via MCT8 could have severe consequences on brain development. The report by Katano-Toki et al, “THRAP3 Interacts With HELZ2 and Plays a Novel Role in Adipocyte Differentiation,” used coimmunoprecipitation coupled with liquid chromatography and tandem mass spectrometry to identify Thrap3 (thyroid hormone receptor-associated protein 3), a putative component of the Mediator/tartrate-resistant acid phosphatase complex, as a Helz2 associating protein. The authors also showed that endogenous Helz2, Thrap3, and peroxisome proliferator-activating receptor(PPAR) associate with each other in mature 3T3-L1 adipocytes. Furthermore, Thrap3 and Helz2 are corecruited to PPAR-response elements within the Fabp4/aP2 and Adipoqenhancers in 3T3-L1 cells in response to PPARligands andcooperativelyenhancePPAR-mediatedgenetranscription in vitro. Thus, Thrap3 is a novel PPAR cofactor that plays an important role in the terminal differentiation of adipocytes. “An Essential Role for Insulin and IGF1 Receptors in Regulating Sertoli Cell Proliferation, Testis Size, and FSH Action in Mice” by Pitetti et al provides in vivo evidence that IGFs are the major regulators of Sertoli cell number and testis size in mammals. Both the insulin receptor and the type I IGF1 receptor are required to obtain an optimal number of adult Sertoli cells and testis size. It was also found that the pituitary hormone FSH requires the insulin/IGF1 signaling pathway to mediate its proliferative effects on immature Sertoli cells and thus testis size. These resultssuggestthatgermcellsthemselvesmayregulatethe number of Sertoli cells and thus testis size and daily sperm outputthroughthesecretionofgrowthfactorspromoting Sertoli cell survival and maturation during postnatal testicular development. Congratulations to these researchers as well as those who produced all of the outstanding science in the May issue.