Matthew J. Fuxjager, Jae-Hyung Lee, Tak-Ming Chan, J. Bahn, Jenifer G. Chew, X. Xiao, B. Schlinger
{"title":"Research Resource: Hormones, Genes, and Athleticism: Effect of Androgens on the Avian Muscular Transcriptome.","authors":"Matthew J. Fuxjager, Jae-Hyung Lee, Tak-Ming Chan, J. Bahn, Jenifer G. Chew, X. Xiao, B. Schlinger","doi":"10.1210/me.2015-1270","DOIUrl":"https://doi.org/10.1210/me.2015-1270","url":null,"abstract":"Male vertebrate social displays vary from physically simple to complex, with the latter involving exquisite motor command of the body and appendages. Studies of these displays have, in turn, provided substantial insight into neuromotor mechanisms. The neotropical golden-collared manakin (Manacus vitellinus) has been used previously as a model to investigate intricate motor skills because adult males of this species perform an acrobatic and androgen-dependent courtship display. To support this behavior, these birds express elevated levels of androgen receptors (AR) in their skeletal muscles. Here we use RNA sequencing to explore how testosterone (T) modulates the muscular transcriptome to support male manakin courtship displays. In addition, we explore how androgens influence gene expression in the muscles of the zebra finch (Taenopygia guttata), a model passerine bird with a limited courtship display and minimal muscle AR. We identify androgen-dependent, muscle-specific gene regulation in both species. In addition, we identify manakin-specific effects that are linked to muscle use during the manakin display, including androgenic regulation of genes associated with muscle fiber contractility, cellular homeostasis, and energetic efficiency. Overall, our results point to numerous genes and gene networks impacted by androgens in male birds, including some that underlie optimal muscle function necessary for performing acrobatic display routines. Manakins are excellent models to explore gene regulation promoting athletic ability.","PeriodicalId":18812,"journal":{"name":"Molecular endocrinology","volume":"30 2 1","pages":"254-71"},"PeriodicalIF":0.0,"publicationDate":"2016-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1210/me.2015-1270","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66016145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Hurt, S. Suzuki, T. Mayama, E. Charmandari, T. Kino
{"title":"Structural Analysis on the Pathologic Mutant Glucocorticoid Receptor Ligand-Binding Domains.","authors":"D. Hurt, S. Suzuki, T. Mayama, E. Charmandari, T. Kino","doi":"10.1210/me.2015-1177","DOIUrl":"https://doi.org/10.1210/me.2015-1177","url":null,"abstract":"Glucocorticoid receptor (GR) gene mutations may cause familial or sporadic generalized glucocorticoid resistance syndrome. Most of the missense forms distribute in the ligand-binding domain and impair its ligand-binding activity and formation of the activation function (AF)-2 that binds LXXLL motif-containing coactivators. We performed molecular dynamics simulations to ligand-binding domain of pathologic GR mutants to reveal their structural defects. Several calculated parameters including interaction energy for dexamethasone or the LXXLL peptide indicate that destruction of ligand-binding pocket (LBP) is a primary character. Their LBP defects are driven primarily by loss/reduction of the electrostatic interaction formed by R611 and T739 of the receptor to dexamethasone and a subsequent conformational mismatch, which deacylcortivazol resolves with its large phenylpyrazole moiety and efficiently stimulates transcriptional activity of the mutant receptors with LBP defect. Reduced affinity of the LXXLL peptide to AF-2 is caused mainly by disruption of the electrostatic bonds to the noncore leucine residues of this peptide that determine the peptide's specificity to GR, as well as by reduced noncovalent interaction against core leucines and subsequent exposure of the AF-2 surface to solvent. The results reveal molecular defects of pathologic mutant receptors and provide important insights to the actions of wild-type GR.","PeriodicalId":18812,"journal":{"name":"Molecular endocrinology","volume":"30 2 1","pages":"173-88"},"PeriodicalIF":0.0,"publicationDate":"2016-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1210/me.2015-1177","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66016114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Alice K Treen, V. Luo, J. Chalmers, P. Dalvi, D. Tran, Wenqing Ye, G. Kim, Z. Friedman, D. Belsham
{"title":"Divergent Regulation of ER and Kiss Genes by 17β-Estradiol in Hypothalamic ARC Versus AVPV Models.","authors":"Alice K Treen, V. Luo, J. Chalmers, P. Dalvi, D. Tran, Wenqing Ye, G. Kim, Z. Friedman, D. Belsham","doi":"10.1210/me.2015-1189","DOIUrl":"https://doi.org/10.1210/me.2015-1189","url":null,"abstract":"Kisspeptin (Kiss) and G-protein-coupled receptor (Gpr)54 have emerged as key regulators of reproduction. 17β-estradiol (E2)-mediated regulation of these neurons is nuclei specific, where anteroventral periventricular (AVPV) Kiss neurons are positively regulated by E2, whereas arcuate nucleus (ARC) neurons are inhibited. We have generated immortalized Kiss cell lines from male and female adult-derived murine hypothalamic primary culture, as well as cell lines from microdissected AVPV and ARC from female Kiss-green fluorescent protein (GFP) mice. All exhibit endogenous Kiss-1 expression, estrogen receptors (ER)s (ERα, ERβ, and Gpr30), as well as known markers of AVPV Kiss neurons in the mHypoA-50 and mHypoA-Kiss/GFP-4, vs markers of ARC Kiss neurons in the mHypoA-55 and the mHypoA-Kiss/GFP-3 lines. There was an increase in Kiss-1 mRNA expression at 24 hours in the AVPV lines and a repression of Kiss-1 mRNA at 4 hours in the ARC lines. An E2-mediated decrease in ERα mRNA expression at 24 hours in the AVPV cell lines was detected, and a significant decrease in Gpr30, ERα, and ERβ mRNA levels at 4 hours in the ARC cell lines was evident. ER agonists and antagonists determined the specific ERs responsible for mediating changes in gene expression. In the AVPV, ERα is required but not ERβ or GPR30, vs the ARC Kiss-expressing cell lines that require GPR30, and either ERα and/or ERβ. We determined cAMP response element-binding protein 1 was necessary for the down-regulation of Kiss-1 mRNA expression using small interfering RNA knockdown in the ARC cell model. These studies elucidate some of the molecular events involved in the differential E2-mediated regulation of unique and specific Kiss neuronal models.","PeriodicalId":18812,"journal":{"name":"Molecular endocrinology","volume":"30 2 1","pages":"217-33"},"PeriodicalIF":0.0,"publicationDate":"2016-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1210/me.2015-1189","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66016172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Makiko Fukaya, C. Brorsson, Kira Meyerovich, L. Catrysse, Diane Delaroche, E. Vanzela, F. Ortis, R. Beyaert, L. Nielsen, M. L. Andersen, H. Mortensen, F. Pociot, G. van Loo, J. Størling, A. K. Cardozo
{"title":"A20 Inhibits β-Cell Apoptosis by Multiple Mechanisms and Predicts Residual β-Cell Function in Type 1 Diabetes.","authors":"Makiko Fukaya, C. Brorsson, Kira Meyerovich, L. Catrysse, Diane Delaroche, E. Vanzela, F. Ortis, R. Beyaert, L. Nielsen, M. L. Andersen, H. Mortensen, F. Pociot, G. van Loo, J. Størling, A. K. Cardozo","doi":"10.1210/me.2015-1176","DOIUrl":"https://doi.org/10.1210/me.2015-1176","url":null,"abstract":"Activation of the transcription factor nuclear factor kappa B (NFkB) contributes to β-cell death in type 1 diabetes (T1D). Genome-wide association studies have identified the gene TNF-induced protein 3 (TNFAIP3), encoding for the zinc finger protein A20, as a susceptibility locus for T1D. A20 restricts NF-κB signaling and has strong antiapoptotic activities in β-cells. Although the role of A20 on NF-κB inhibition is well characterized, its other antiapoptotic functions are largely unknown. By studying INS-1E cells and rat dispersed islet cells knocked down or overexpressing A20 and islets isolated from the β-cell-specific A20 knockout mice, we presently demonstrate that A20 has broader effects in β-cells that are not restricted to inhibition of NF-κB. These involves, suppression of the proapoptotic mitogen-activated protein kinase c-Jun N-terminal kinase (JNK), activation of survival signaling via v-akt murine thymoma viral oncogene homolog (Akt) and consequently inhibition of the intrinsic apoptotic pathway. Finally, in a cohort of T1D children, we observed that the risk allele of the rs2327832 single nucleotide polymorphism of TNFAIP3 predicted lower C-peptide and higher hemoglobin A1c (HbA1c) levels 12 months after disease onset, indicating reduced residual β-cell function and impaired glycemic control. In conclusion, our results indicate a critical role for A20 in the regulation of β-cell survival and unveil novel mechanisms by which A20 controls β-cell fate. Moreover, we identify the single nucleotide polymorphism rs2327832 of TNFAIP3 as a possible prognostic marker for diabetes outcome in children with T1D.","PeriodicalId":18812,"journal":{"name":"Molecular endocrinology","volume":"46 1","pages":"48-61"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1210/me.2015-1176","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66016105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Table of Contents.","authors":"intellipap de DeVilbiss","doi":"10.1210/mend.2016.30.issue-8.toc","DOIUrl":"https://doi.org/10.1210/mend.2016.30.issue-8.toc","url":null,"abstract":"","PeriodicalId":18812,"journal":{"name":"Molecular endocrinology","volume":"30 8 1","pages":"5A-6A"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66020922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Editorial: Centennial Celebration - An Interview With Professor Evan Simpson on Hormones and Cancer.","authors":"","doi":"10.1210/me.2016-1126","DOIUrl":"https://doi.org/10.1210/me.2016-1126","url":null,"abstract":"","PeriodicalId":18812,"journal":{"name":"Molecular endocrinology","volume":"30 10 1","pages":"1013-1014"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1210/me.2016-1126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66016811","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jing Li, Jun Song, H. Weiss, Todd Weiss, C. Townsend, B. Evers
{"title":"Activation of AMPK Stimulates Neurotensin Secretion in Neuroendocrine Cells.","authors":"Jing Li, Jun Song, H. Weiss, Todd Weiss, C. Townsend, B. Evers","doi":"10.1210/me.2015-1094","DOIUrl":"https://doi.org/10.1210/me.2015-1094","url":null,"abstract":"AMP-activated protein kinase (AMPK), a critical fuel-sensing enzyme, regulates the metabolic effects of various hormones. Neurotensin (NT) is a 13-amino acid peptide predominantly localized in enteroendocrine cells of the small bowel and released by fat ingestion. Increased fasting plasma levels of pro-NT (a stable NT precursor fragment produced in equimolar amounts relative to NT) are associated with an increased risk of diabetes, cardiovascular disease, and mortality; however, the mechanisms regulating NT release are not fully defined. We previously reported that inhibition of the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) increases NT secretion and gene expression through activation of the MEK/ERK pathway. Here, we show that activation of AMPK increases NT secretion from endocrine cell lines (BON and QGP-1) and isolated mouse crypt cells enriched for NT-positive cells. In addition, plasma levels of NT increase in mice treated with 5-aminoimidazole-4-carboxamide riboside, a pharmacologic AMPK activator. Small interfering RNA-mediated knockdown of AMPKα decrease, whereas overexpression of the subunit significantly enhances, NT secretion from BON cells treated with AMPK activators or oleic acid. Similarly, small interfering RNA knockdown of the upstream AMPK kinases, liver kinase B1 and Ca(2+) calmodulin-dependent protein kinase kinase 2, also attenuate NT release and AMPK phosphorylation. Moreover, AMPK activation increases NT secretion through inhibition of mTORC1 signaling. Together, our findings show that AMPK activation enhances NT release through inhibition of mTORC1 signaling, thus demonstrating an important cross talk regulation for NT secretion.","PeriodicalId":18812,"journal":{"name":"Molecular endocrinology","volume":"30 1 1","pages":"26-36"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1210/me.2015-1094","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66015867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Table of Contents.","authors":"J. Huseynov, Committee Chair","doi":"10.1210/mend.2016.30.issue-2.toc","DOIUrl":"https://doi.org/10.1210/mend.2016.30.issue-2.toc","url":null,"abstract":"The dissertation of Javid J. Huseynov is approved and is acceptable in quality and form for publication on microfilm and in digital formats: ii DEDICATION To my mother and to all others that are dear to me...","PeriodicalId":18812,"journal":{"name":"Molecular endocrinology","volume":"30 2 1","pages":"4A-5A"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66020558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Derick Albers, Joseph Belisle, Akshay Chakravarthy, Edward Y. Chen, Abigayle Farris Dang, Benjamin Daniels, John Evans, Aaron K. Block, Annabel R. Chang, Laura Crane, David A. Curfman, Lisa Nunn DeBord, Nicholas J. Demeropolis, Alexander S. Elson, Justin K. Gelfand, Kevin R. Grondahl, M. Grossmann, A. R. Hansberry, Eric J. Andalman, M. Mailloux, J. R. Mourning, John J. Schoemehl, S. Papacostas, Elizabeth A. Peters, Melissa A. Reinckens, Daniel S. Riemer, Michael Rueckheim, Adrienne E. Van Winkle, Elizabeth White, Benjamin D. Sandahl, K. Schopp, J. Seeder, Anne J. Siarnacki, Benjamin J. Siders, Megan A. Sindel, Jessica J. Smith, S. Solimani, D. Spira, Scott Talkov, Wakaba Tessier, Daniel Tierney, Elizabeth K. Tomasovic, J. V. Duren, Miriam Volchenboum, Alana C. Hake, Jefferson Hayden, Elisheva Hirshman-Green, Amanda Katzenstein, Corinne Mattli, Amanda Norris, Nathan R. Jones, Rebecca J. Keyworth, Michael E. Klenov, Aditi D. Kothekar, S. Kuehnel, Kate M Lesciotto, Steven K. Luther, Colman Mccarthy, Jessica
{"title":"Editorial Board.","authors":"Derick Albers, Joseph Belisle, Akshay Chakravarthy, Edward Y. Chen, Abigayle Farris Dang, Benjamin Daniels, John Evans, Aaron K. Block, Annabel R. Chang, Laura Crane, David A. Curfman, Lisa Nunn DeBord, Nicholas J. Demeropolis, Alexander S. Elson, Justin K. Gelfand, Kevin R. Grondahl, M. Grossmann, A. R. Hansberry, Eric J. Andalman, M. Mailloux, J. R. Mourning, John J. Schoemehl, S. Papacostas, Elizabeth A. Peters, Melissa A. Reinckens, Daniel S. Riemer, Michael Rueckheim, Adrienne E. Van Winkle, Elizabeth White, Benjamin D. Sandahl, K. Schopp, J. Seeder, Anne J. Siarnacki, Benjamin J. Siders, Megan A. Sindel, Jessica J. Smith, S. Solimani, D. Spira, Scott Talkov, Wakaba Tessier, Daniel Tierney, Elizabeth K. Tomasovic, J. V. Duren, Miriam Volchenboum, Alana C. Hake, Jefferson Hayden, Elisheva Hirshman-Green, Amanda Katzenstein, Corinne Mattli, Amanda Norris, Nathan R. Jones, Rebecca J. Keyworth, Michael E. Klenov, Aditi D. Kothekar, S. Kuehnel, Kate M Lesciotto, Steven K. Luther, Colman Mccarthy, Jessica ","doi":"10.1210/mend.2016.30.issue-7.edboard","DOIUrl":"https://doi.org/10.1210/mend.2016.30.issue-7.edboard","url":null,"abstract":"","PeriodicalId":18812,"journal":{"name":"Molecular endocrinology","volume":"30 7 1","pages":"3A"},"PeriodicalIF":0.0,"publicationDate":"2016-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66021350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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