Article
Endocrinology & Metabolism
Yuta Tezuka, Nanako Atsumi, Amy R. Blinder, Juilee Rege, Thomas J. Giordano, William E. Rainey, Adina F. Turcu
Summary: Unlike the ZG and ZR, the ZF and the total adrenal cortex areas enlarge with aging. An abrupt decline of the ZG occurs with age in men only, possibly contributing to sexual dimorphism in cardiovascular risk.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2021)
Article
Peripheral Vascular Disease
Elle van de Wiel, Amir-Hossein Chaman Baz, Benno Kuesters, Kuniaki Mukai, Lidia van Bonzel, Merijn van Erp, Jaap Deinum, Johan Langenhuijsen
Summary: Based on the research on human ZG, we found that there is a correlation between age and CYP11B2 expression. As age increases, the relative CYP11B2 expressing area decreases, continuity decreases, gap length and CYP11B2 depth increase. These changes may indicate the involution of ZG and the formation of aldosterone-producing micronodules, and they occur bilaterally.
Article
Biochemistry & Molecular Biology
Kang-Yung Peng, Hung-Wei Liao, Jeff S. Chueh, Chien-Yuan Pan, Yen-Hung Lin, Yung-Ming Chen, Peng-Ying Chen, Chun-Lin Huang, Vin-Cent Wu
Summary: Mutated KCNJ5 channel plays a crucial role in the pathogenesis of aldosterone-producing adenoma, disrupting potassium ion selectivity and increasing autonomous aldosterone production. Immunohistochemical and patch-clamp experiments confirmed the functional properties of the mutation, while macrolide antibiotics were ineffective in interfering with the aberrant electrophysiological properties induced by the mutation.
Article
Endocrinology & Metabolism
Kazuki Nakai, Katsunori Manaka, Junichiro Sato, Maki Takeuchi, Yuto Yamazaki, Hironobu Sasano, Yuya Tsurutani, Jun Saito, Tetsuo Nishikawa, Taroh Ri, Masaomi Nangaku, Noriko Makita
Summary: This study investigates the association between the size and aldosterone-producing ability of aldosterone-producing adenomas. The results suggest that larger tumors have higher aldosterone-producing ability, and there are differences in pathology and gene mutations.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Review
Physiology
Paula Q. Barrett, Nick A. Guagliardo, Douglas A. Bayliss
Summary: Excessive aldosterone plays a role in hypertensive disorders, with mutations in ion channels contributing to the activation of zona glomerulosa cells. While dispersed ZG cells exhibit electrically quiescent behavior, ZG cells in native rosette structures are electrically excitable, generating periodic voltage spikes and bursts of Ca2+ oscillations. Understanding how a variety of conductances underlie these oscillations and how the rosette orchestrates the behavior of a functional network to control aldosterone secretion is a challenge for future research.
ANNUAL REVIEW OF PHYSIOLOGY, VOL 83
(2021)
Article
Cell Biology
Sining Leng, Diana L. Carlone, Nick A. Guagliardo, Paula Q. Barrett, David T. Breault
Summary: This article reviews the morphological features of the adrenal zona glomerulosa (zG) and recent cellular and molecular discoveries governing its formation, highlighting the organization of zG cells into rosettes and their impact on adrenal function. It discusses how rosettes arise through constriction at common cellular contact points and the role of adherens junctions in this process, as well as the invagination and folding of flat sheet-like domains in the nascent zG that give rise to compact round glomeruli in the adult zG.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Shogo Harashima, Yuto Yamazaki, Naoki Motomura, Yoshikiyo Ono, Kei Omata, Yuta Tezuka, Ryo Morimoto, Yasuhiro Nakamura, Fumitoshi Satoh, Hiroyoshi Suzuki, Go Eun Kwon, Man Ho Choi, Hironobu Sasano
Summary: This study analyzed the histological characteristics, cholesterol metabolism, and differences related to gene mutations in aldosterone-producing adenomas (APAs). The results showed that mutated KCNJ5 genes in APAs were associated with higher plasma aldosterone concentration and more lipid droplets in compact tumor cells compared to non-mutated APAs. Additionally, cholesterol uptake and synthesis were found to be different between clear and compact tumor cells, with mutated KCNJ5 APAs showing enhanced cholesterol ester uptake and de novo synthesis.
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
(2022)
Article
Peripheral Vascular Disease
Christina A. Gancayco, Molly R. Gerding, David T. Breault, Mark P. Beenhakker, Paula O. Barrette, Nick A. Guagliardo
Summary: This study investigated the relationship between ion channel dysfunction in aldosterone-producing cells and autonomous aldosterone production. The results showed that channel dysfunction can lead to spontaneous calcium oscillatory activity and drive substantial autonomous aldosterone production.
Article
Endocrinology & Metabolism
Liling Zhao, Jinjing Wan, Yujun Wang, Wenjun Yang, Qi Liang, Jinrong Wang, Ping Jin
Summary: This study presents a rare case of co-existing Cushing's syndrome and primary aldosteronism caused by bilateral adrenocortical adenomas secreting aldosterone and cortisol. Through clinical examinations and pathological analysis, it was found that the heterogeneity of tumor cell compositions and a mutation in the KCNJ5 gene may have led to different hormone secretions in the bilateral adrenal adenomas.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Anatomy & Morphology
Yumin Zhu, Xuefeng Zhang, Changlong Hu
Summary: Recent studies in mouse models have shown that the multi-cellular rosette structure of the adrenal zona glomerulosa (ZG) is crucial for aldosterone production by ZG cells. However, the rosette structure of human ZG has remained unclear. This study investigated the rosette structure of human adrenal with and without aldosterone-producing cell clusters (APCCs) and found that cells in APCCs form larger rosettes through enhanced adherens junctions. This study provides the first detailed characterization of the rosette structure of human adrenal ZG and suggests that the multi-cellular rosette structure may also be necessary for aldosterone production in APCCs.
JOURNAL OF ANATOMY
(2023)
Article
Multidisciplinary Sciences
Celine Duparc, Pamela Camponova, Malanie Roy, Herve Lefebvre, Michael Thomas
Summary: This research used immunohistochemical analyses to investigate the remodeling of the adrenal cortex in relation to aging. The results showed a lack of continuity in the functional zone between zona glomerulosa (ZG) and zona fasciculata (ZF) in younger individuals, but the development of aldosterone-producing micronodules (APMs) in older individuals. The study also found that steroidogenic cells are distributed throughout the cortex and medulla, suggesting that the functional zonation is not solely maintained by cell lineage conversion/migration.
Article
Endocrinology & Metabolism
Emma Roth, Simon Benoit, Baptiste Quentin, Brian Lam, Sarah Will, Marcella Ma, Nick Heeley, Tamana Darwish, Yashaswi Shrestha, Fiona Gribble, Frank Reimann, Irina Pshenichnaya, Giles Yeo, David J. Baker, James L. Trevaskis, Clemence Blouet
Summary: Combinatorial therapy of GLP-1R and CCK1R agonists in the brain was found to enhance rapid and sustained appetite suppression and weight loss by engaging specific neuronal populations, such as NTS/AP Calcrlthorn neurons, in discrete brain nuclei including the NTS.
MOLECULAR METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Mar Quinones, Rene Hernandez-Bautista, Daniel Beiroa, Violeta Heras, Francisco L. Torres-Leal, Brian Y. H. Lam, Ana Senra, Johan Ferno, Alicia Garcia Gomez-Valades, Markus Schwaninger, Vincent Prevot, Giles Yeo, Marc Claret, Miguel Lopez, Carlos Dieguez, Omar Al-Massadi, Ruben Nogueiras
Summary: SIRT3 in the hypothalamus, specifically in POMC neurons, plays a key role in regulating energy balance, leading to improved metabolic parameters and negative energy balance in male mice.
Article
Endocrinology & Metabolism
Georgina K. C. Dowsett, Brian Y. H. Lam, John A. Tadross, Irene Cimino, Debra Rimmington, Anthony P. Coll, Joseph Polex-Wolf, Lotte Bjerre Knudsen, Charles Pyke, Giles S. H. Yeo
Summary: This study provides a detailed single-cell level characterization of cells in the AP and NTS expressing receptors for key anti-obesity drugs, revealing their gene expression profiles under different nutritional states. The research also identifies the transcriptional sensitivity of oligodendrocytes to overnight fasting and shows that roughly half of GIPR-expressing cells are oligodendrocytes.
MOLECULAR METABOLISM
(2021)
Article
Biochemistry & Molecular Biology
Kaitlin H. Wade, Brian Y. H. Lam, Audrey Melvin, Warren Pan, Laura J. Corbin, David A. Hughes, Kara Rainbow, Jian-Hua Chen, Katie Duckett, Xiaoming Liu, Jacek Mokrosinski, Alexander Morseburg, Sam Neaves, Alice Williamson, Chen Zhang, I. Sadaf Farooqi, Giles S. H. Yeo, Nicholas J. Timpson, Stephen O'Rahilly
Summary: Mutations in the MC4R gene are associated with obesity, with the frequency of LoF mutations being higher than previously estimated. Carriers of such mutations may enter adulthood with a significant burden of excess adiposity.
Article
Cell & Tissue Engineering
Maki Asami, Brian Y. H. Lam, Marcella K. Ma, Kara Rainbow, Stefanie Braun, Matthew D. VerMilyea, Giles S. H. Yeo, Anthony C. F. Perry
Summary: Human embryonic transcription initiates at the one-cell stage, sooner than previously thought, with both upregulation and downregulation of genes impacting early development processes.
Article
Multidisciplinary Sciences
B. Y. H. Lam, A. Williamson, S. Finer, F. R. Day, J. A. Tadross, A. Goncalves Soares, K. Wade, P. Sweeney, M. N. Bedenbaugh, D. T. Porter, A. Melvin, K. L. J. Ellacott, R. N. Lippert, S. Buller, J. Rosmaninho-Salgado, G. K. C. Dowsett, K. E. Ridley, Z. Xu, I. Cimino, D. Rimmington, K. Rainbow, K. Duckett, S. Holmqvist, A. Khan, X. Dai, E. G. Bochukova, R. C. Trembath, H. C. Martin, A. P. Coll, D. H. Rowitch, N. J. Wareham, D. A. van Heel, N. Timpson, R. B. Simerly, K. K. Ong, R. D. Cone, C. Langenberg, J. R. B. Perry, G. S. Yeo, S. O'Rahilly
Summary: MC3R regulates the timing of sexual maturation, linear growth rate, and accrual of lean mass, while MC4R controls appetite, food intake, and energy expenditure. Loss of MC3R leads to delayed puberty, reduced linear growth, and decreased lean mass, while loss of MC4R results in delayed sexual maturation and insensitivity of reproductive cycle length to nutritional perturbation.
Article
Clinical Neurology
Alana M. Thackray, Brian Lam, Erin E. McNulty, Amy Nalls, Candace K. Mathiason, Srivathsa Subramanya Magadi, Walker S. Jackson, Olivier Andreoletti, Cristobal Marrero-Winkens, Hermann Schatzl, Raymond Bujdoso
Summary: This study finds that increased activity of the Hsp70 protein disaggregase system can clear human prions and neurotoxicity, establishing it as a potential therapeutic target for human prion disease.
Review
Cell Biology
Anthony C. F. Perry, Maki Asami, Brian Y. H. Lam, Giles S. H. Yeo
Summary: Gamete genomes are silent until embryonic genome activation (EGA) after fertilization. Recent findings suggest that EGA is triggered in one-cell embryos by fertilization. Post-translational modifications during fertilization may activate transcriptionally favorable chromatin and oocyte-derived transcription factors to initiate EGA. Cancer-associated pathways and genes upregulated by cancer-associated transcription factors suggest a mechanistic link between EGA and the trajectory to cancer.
TRENDS IN CELL BIOLOGY
(2023)
Article
Endocrinology & Metabolism
Katie Duckett, Alice Williamson, John W. R. Kincaid, Kara Rainbow, Laura J. Corbin, Hilary C. Martin, Ruth Y. Eberhardt, Qin Qin Huang, Matthew E. Hurles, Wen He, Raja Brauner, Angela Delaney, Leo Dunkel, Romina P. Grinspon, Janet E. Hall, Joel N. Hirschhorn, Sasha R. Howard, Ana C. Latronico, Alexander A. L. Jorge, Ken McElreavey, Veronica Mericq, Paulina M. Merino, Mark R. Palmert, Lacey Plummer, Rodolfo A. Rey, Raissa C. Rezende, Stephanie B. Seminara, Kathryn Salnikov, Indraneel Banerjee, Brian Y. H. Lam, John R. B. Perry, Nicholas J. Timpson, Peter Clayton, Yee-Ming Chan, Ken K. Ong, Stephen O'Rahilly
Summary: Deleterious variants in MC3R are more frequently found in patients with constitutional delay of growth and puberty (CDGP) compared to normosmic idiopathic hypogonadotropic hypogonadism (nIHH). However, these variants are not a common cause of CDGP.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Meeting Abstract
Peripheral Vascular Disease
Kha Chin Long, Norlela Sukor, Geok Chin Tan, Nor Azian Abdul Murad, Morris Jonathan Brown, Elena Aisha Azizan
JOURNAL OF HYPERTENSION
(2023)
Meeting Abstract
Peripheral Vascular Disease
Siti Khadijah Syed Mohammed Nazri, Rozman Zakaria, Nor Azian Abdul Murad, Rohaizak Muhammad, Geok Chin Tan, Norlela Sukor, Elena Aisha Azizan
JOURNAL OF HYPERTENSION
(2023)
Meeting Abstract
Peripheral Vascular Disease
Fatin Athirah Pauzi, Elena Aisha Azizan, Muaatamarulain Mustangin, Geok Chin Tan, Norlela Sukor, Ales Ryska, Jiri Ceral, Miroslav Solar, Azraai Bahari Nasruddin
JOURNAL OF HYPERTENSION
(2023)
Meeting Abstract
Peripheral Vascular Disease
Nurfatin Syazreen Mohd Rizam, Muaatamarulain Mustangin, Geok Chin Tan, Norlela Sukor, Fatin Saparuddin, Fatin Athirah Pauzi, Siti Khadijah Syed Muhammad Nazri, Azraai Bahari Nasruddin, Elena Aisha Azizan
JOURNAL OF HYPERTENSION
(2023)
Meeting Abstract
Peripheral Vascular Disease
Elena Aisha Azizan
JOURNAL OF HYPERTENSION
(2023)
Article
Endocrinology & Metabolism
Lukas Steuernagel, Brian Y. H. Lam, Paul Klemm, Georgina K. C. Dowsett, Corinna A. Bauder, John A. Tadross, Tamara Sotelo Hitschfeld, Almudena del Rio Martin, Weiyi Chen, Alain J. de Solis, Henning Fenselau, Peter Davidsen, Irene Cimino, Sara N. Kohnke, Debra Rimmington, Anthony P. Coll, Andreas Beyer, Giles S. H. Yeo, Jens C. Bruening
Summary: The hypothalamus plays a crucial role in coordinating fundamental body functions, but there is still a lack of unified catalog and molecular characterization of neuronal subtypes in this brain region. The integrated reference atlas "HypoMap" provides a systematic framework for functional annotation of hypothalamic cell types, serving as a crucial platform for unraveling the functional organization of hypothalamic neurocircuits and identifying druggable targets for treating metabolic disorders.