The following studies, among others, will be published in Endocrine Society journals. Before print, they are edited and posted online in each journal’s Early Release section. You can access the journals at www.endocrine.org.
Penetrance and Clinical Features of Pheochromocytoma in a Six-Generation Family Carrying a Germline TMEM127 Mutation • Sergio P. A. Toledo, Delmar M. Lourenço, Jr., Tomoko Sekiya, Antonio M. Lucon, Renato C. Baena, Claudio C. Castro, Luiz A. Bortolotto, Maria C. N. Zerbini, Sheila A. C. Siqueira, Rodrigo A. Toledo, and Patricia L. M. Dahia • Tumor multicentricity, nodular adrenomedullary hyperplasia, and the occurrence of symptoms more than a decade earlier than the age at diagnosis are novel findings in TMEM127-related PHEO. The high penetrance of pheochromocytoma in this condition validates the benefits of genetic testing of at-risk relatives. We thus recommend that TMEM127 genetic testing should be offered to at-risk individuals at age 22 years and mutation carriers should undergo clinical surveillance annually.
The Novel Heat Shock Protein 90 Inhibitor NVP-AUY922 Synergizes with the Histone Deacetylase Inhibitor PXD101 in Induction of Death of Anaplastic Thyroid Carcinoma Cells • Si Hyoung Kim, Jun Goo Kang, Chul Sik Kim, Sung-Hee Ihm, Moon Gi Choi, Hyung Joon Yoo, and Seong Jin Lee • Our results demonstrate that AUY922 potently induces cytotoxicity with concomitant modulation of hsp90 client proteins in ATC cells. Moreover, AUY922 has a synergistic activity with PXD101 in induction of cytotoxicity in conjunction with the inactivation of PI3K/Akt signaling and surviving and the activation of DNA damage response in ATC cells.
Smoking as an Effect Modifier of the Association of Calcium Intake with Bone Mineral Density • Lutz P. Breitling • Even though the present results cannot rule out that smoking-associated differences in calcium absorption exist, they do suggest that smoking behavior does not have any relevant impact on the beneficial effects of calcium intake on bone mineral density at the population level.
Mitigating or Exacerbating Effects of Maternal-Fetal Programming of Female Mice Through the Food Choice Environment • Bonnie Brenseke, Javiera Bahamonde, Michael Talanian, Ellie Kornfeind, Jacquiline Daly, Grayson Cobb, Jinhua Zhang, M. Renee Prater, George C. Davis, and Deborah J. Good • The model defined herein can be used as the basis for future studies to characterize the cycle of inter- and intragenerational obesity, and whether more realistic diet environments, especially those including choice, can mitigate phenotype.
AGEs-RAGE System Downregulates Sirt1 Through the Ubiquitin-Proteasome Pathway to Promote FN and TGF-ß1 Expression in Male Rat Glomerular Mesangial Cells • Kai-Peng Huang, Cheng Chen, Jie Hao, Jun-Ying Huang, Pei-Qing Liu, and He-Qing Huang • These results indicated that the AGEs-RAGE system increased the ubiquitination and subsequent proteasome-mediated degradation of Sirt1 by reducing USP22 level, and AGEsRAGE-USP22-Sirt1 formed a cascade pathway that regulated FN and TGF-ß1 level, which participated in the pathological progression of diabetic nephropathy.
Measurement of Testosterone by Immunoassays and Mass Spectrometry in Mouse Serum, Testicular and Ovarian Extracts • David J. Handelsman, Mark Jimenez, Gurmeet K. S. Singh, Jenny Spaliviero, Reena Desai, and Kirsty A. Walters • The authors conclude that these direct testosterone immunoassay kits provide relatively, but not absolutely, accurate results with male mouse serum and testis extracts but not with female mouse serum and ovary extracts, with performance improved by pre-assay extraction. Whether relative accuracy is fit for purpose depends on the experimental aims, design, and interpretation.
In Vitro and Mouse Studies Supporting Therapeutic Utility of Triiodothyroacetic Acid in MCT8 Deficiency • Simone Kersseboom, Sigrun Horn, W. Edward Visser, Jiesi Chen, Edith C. H. Friesema, Catherine Vaurs-Barrière, Robin P. Peeters, Heike Heuer, and Theo J. Visser • The authors demonstrated uptake of TA3 in neuronal cells and in fibroblasts of MCT8 patients and similar gene responses to T3 and TA3. This indicates that TA3 bypasses MCT8 and may be used to improve the neural status of MCT8 patients.
Thermogenic Activity of UCP1 in Human White Fat-Derived Beige Adipocytes • Stefano Bartesaghi, Stefan Hallen, Li Huang, Per-Arne Svensson, Remi A. Momo, Simonetta Wallin, Eva K. Carlsson, Anna Forslöw, Patrick Seale, and Xiao-Rong Peng • This study reveals that hASCs can be readily differentiated into beige adipocytes that, upon activation, undergo uncoupling protein 1-dependent thermogenesis.
Persistent ERK/MAPK Activation Promotes Lactotrope Differentiation and Diminishes Tumorigenic Phenotype • Allyson Booth, Tammy Trudeau, Crystal Gomez, M. Scott Lucia, and Arthur Gutierrez-Hartmann • These data demonstrate that activated MAPK promotes differentiation and is not sufficient to drive tumorigenesis, suggesting that pituitary lactotrope tumor cells have the ability to evade the tumorigenic fate that is often associated with Ras/MAPK activation.