ArticleThe Journal of clinical endocrinology and metabolism2015
LGR5 Activates Noncanonical Wnt Signaling and Inhibits Aldosterone Production in the Human Adrenal.
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Article in The Journal of clinical endocrinology and metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22citing papers in PubMed
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22 citing papers in PubMed, 37 citations in OpenAlex.
- Human adrenocortical organoids for tissue regeneration and disease modeling.Stem cell reports · 2025Article
- Single-nucleus and spatial transcriptome reveal adrenal homeostasis in normal and tumoural adrenal glands.Clinical and translational medicine · 2024Article
- Personalized Driver Gene Prediction Using Graph Convolutional Networks with Conditional Random Fields.Biology · 2024Article
- Aging induces region-specific dysregulation of hormone synthesis in the primate adrenal gland.Nature aging · 2024Article
- Evaluating the role of aldosterone synthesis on adrenal cell fate.Frontiers in endocrinology · 2024Review
- Primary aldosteronism: molecular medicine meets public health.Nature reviews. Nephrology · 2023Review
- Article
- RNA-Seq reveals ACTH-induced steroid hormone pathway participating in goat adrenal gland response to castration.Scientific reports · 2023Article
- Somatic mutations of CADM1 in aldosterone-producing adenomas and gap junction-dependent regulation of aldosterone production.Nature genetics · 2023Article
- Disruption of stem cell niche-confined R-spondin 3 expression leads to impaired hematopoiesis.Blood advances · 2023Article
- Ectopic localization of CYP11B1 and CYP11B2-expressing cells in the normal human adrenal gland.PloS one · 2022Article
- Primary aldosteronism: Pathophysiological mechanisms of cell death and proliferation.Frontiers in endocrinology · 2022Review
- Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause.Nature genetics · 2021Article
- ANO4 (Anoctamin 4) Is a Novel Marker of Zona Glomerulosa That Regulates Stimulated Aldosterone Secretion.Hypertension (Dallas, Tex. : 1979) · 2019Article
- Primary Aldosteronism: KCNJ5 Mutations and Adrenocortical Cell Growth.Hypertension (Dallas, Tex. : 1979) · 2019Article
- Targeting LGR5 in Colorectal Cancer: therapeutic gold or too plastic?British journal of cancer · 2018Review
- Review of Markers of Zona Glomerulosa and Aldosterone-Producing Adenoma Cells.Hypertension (Dallas, Tex. : 1979) · 2017Review
- Physiological and Pathological Roles in Human Adrenal of the Glomeruli-Defining Matrix Protein NPNT (Nephronectin).Hypertension (Dallas, Tex. : 1979) · 2017Article
- Cell signaling pathways in the adrenal cortex: Links to stem/progenitor biology and neoplasia.Molecular and cellular endocrinology · 2017Review
- Transcriptome Pathway Analysis of Pathological and Physiological Aldosterone-Producing Human Tissues.Hypertension (Dallas, Tex. : 1979) · 2016Article
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15 authors at 1 institution in 1 country.
Lalarukh Haris ShaikhClinical Pharmacology Unit (L.H.S., J.Z., A.E.D.T., S.G., J.J.M., E.A.B.A., A.P.D., M.J.B.) and Cardiovascular Division (N.F., H.Y., M.R.B.), Department of Medicine, University of Cambridge, Cambridge National Institute for Health Research (S.G.N.), Biomedical Research Centre, Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge Metabolic Research Laboratories (G.S.Y.), Institute of Metabolic Science, Addenbrooke's Hospital, and Human Research Tissue Bank (W.Z.), Cambridge University Hospitals Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Medicine (E.A.B.A.), Faculty of Medicine, The National University of Malaysia Medical Centre, Kuala Lumpur 56000, Malaysia; and Medical Research Council Cancer Unit (G.M.), University of Cambridge, Cambridge CB2 0XZ, United Kingdom.
Junhua ZhouClinical Pharmacology Unit (L.H.S., J.Z., A.E.D.T., S.G., J.J.M., E.A.B.A., A.P.D., M.J.B.) and Cardiovascular Division (N.F., H.Y., M.R.B.), Department of Medicine, University of Cambridge, Cambridge National Institute for Health Research (S.G.N.), Biomedical Research Centre, Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge Metabolic Research Laboratories (G.S.Y.), Institute of Metabolic Science, Addenbrooke's Hospital, and Human Research Tissue Bank (W.Z.), Cambridge University Hospitals Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Medicine (E.A.B.A.), Faculty of Medicine, The National University of Malaysia Medical Centre, Kuala Lumpur 56000, Malaysia; and Medical Research Council Cancer Unit (G.M.), University of Cambridge, Cambridge CB2 0XZ, United Kingdom.
Ada E D TeoClinical Pharmacology Unit (L.H.S., J.Z., A.E.D.T., S.G., J.J.M., E.A.B.A., A.P.D., M.J.B.) and Cardiovascular Division (N.F., H.Y., M.R.B.), Department of Medicine, University of Cambridge, Cambridge National Institute for Health Research (S.G.N.), Biomedical Research Centre, Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge Metabolic Research Laboratories (G.S.Y.), Institute of Metabolic Science, Addenbrooke's Hospital, and Human Research Tissue Bank (W.Z.), Cambridge University Hospitals Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Medicine (E.A.B.A.), Faculty of Medicine, The National University of Malaysia Medical Centre, Kuala Lumpur 56000, Malaysia; and Medical Research Council Cancer Unit (G.M.), University of Cambridge, Cambridge CB2 0XZ, United Kingdom.
Sumedha GargClinical Pharmacology Unit (L.H.S., J.Z., A.E.D.T., S.G., J.J.M., E.A.B.A., A.P.D., M.J.B.) and Cardiovascular Division (N.F., H.Y., M.R.B.), Department of Medicine, University of Cambridge, Cambridge National Institute for Health Research (S.G.N.), Biomedical Research Centre, Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge Metabolic Research Laboratories (G.S.Y.), Institute of Metabolic Science, Addenbrooke's Hospital, and Human Research Tissue Bank (W.Z.), Cambridge University Hospitals Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Medicine (E.A.B.A.), Faculty of Medicine, The National University of Malaysia Medical Centre, Kuala Lumpur 56000, Malaysia; and Medical Research Council Cancer Unit (G.M.), University of Cambridge, Cambridge CB2 0XZ, United Kingdom.
Sudeshna Guha NeogiClinical Pharmacology Unit (L.H.S., J.Z., A.E.D.T., S.G., J.J.M., E.A.B.A., A.P.D., M.J.B.) and Cardiovascular Division (N.F., H.Y., M.R.B.), Department of Medicine, University of Cambridge, Cambridge National Institute for Health Research (S.G.N.), Biomedical Research Centre, Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge Metabolic Research Laboratories (G.S.Y.), Institute of Metabolic Science, Addenbrooke's Hospital, and Human Research Tissue Bank (W.Z.), Cambridge University Hospitals Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Medicine (E.A.B.A.), Faculty of Medicine, The National University of Malaysia Medical Centre, Kuala Lumpur 56000, Malaysia; and Medical Research Council Cancer Unit (G.M.), University of Cambridge, Cambridge CB2 0XZ, United Kingdom.
Nichola FiggClinical Pharmacology Unit (L.H.S., J.Z., A.E.D.T., S.G., J.J.M., E.A.B.A., A.P.D., M.J.B.) and Cardiovascular Division (N.F., H.Y., M.R.B.), Department of Medicine, University of Cambridge, Cambridge National Institute for Health Research (S.G.N.), Biomedical Research Centre, Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge Metabolic Research Laboratories (G.S.Y.), Institute of Metabolic Science, Addenbrooke's Hospital, and Human Research Tissue Bank (W.Z.), Cambridge University Hospitals Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Medicine (E.A.B.A.), Faculty of Medicine, The National University of Malaysia Medical Centre, Kuala Lumpur 56000, Malaysia; and Medical Research Council Cancer Unit (G.M.), University of Cambridge, Cambridge CB2 0XZ, United Kingdom.
Giles S YeoClinical Pharmacology Unit (L.H.S., J.Z., A.E.D.T., S.G., J.J.M., E.A.B.A., A.P.D., M.J.B.) and Cardiovascular Division (N.F., H.Y., M.R.B.), Department of Medicine, University of Cambridge, Cambridge National Institute for Health Research (S.G.N.), Biomedical Research Centre, Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge Metabolic Research Laboratories (G.S.Y.), Institute of Metabolic Science, Addenbrooke's Hospital, and Human Research Tissue Bank (W.Z.), Cambridge University Hospitals Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Medicine (E.A.B.A.), Faculty of Medicine, The National University of Malaysia Medical Centre, Kuala Lumpur 56000, Malaysia; and Medical Research Council Cancer Unit (G.M.), University of Cambridge, Cambridge CB2 0XZ, United Kingdom.
Haixiang YuClinical Pharmacology Unit (L.H.S., J.Z., A.E.D.T., S.G., J.J.M., E.A.B.A., A.P.D., M.J.B.) and Cardiovascular Division (N.F., H.Y., M.R.B.), Department of Medicine, University of Cambridge, Cambridge National Institute for Health Research (S.G.N.), Biomedical Research Centre, Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge Metabolic Research Laboratories (G.S.Y.), Institute of Metabolic Science, Addenbrooke's Hospital, and Human Research Tissue Bank (W.Z.), Cambridge University Hospitals Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Medicine (E.A.B.A.), Faculty of Medicine, The National University of Malaysia Medical Centre, Kuala Lumpur 56000, Malaysia; and Medical Research Council Cancer Unit (G.M.), University of Cambridge, Cambridge CB2 0XZ, United Kingdom.
Janet J MaguireClinical Pharmacology Unit (L.H.S., J.Z., A.E.D.T., S.G., J.J.M., E.A.B.A., A.P.D., M.J.B.) and Cardiovascular Division (N.F., H.Y., M.R.B.), Department of Medicine, University of Cambridge, Cambridge National Institute for Health Research (S.G.N.), Biomedical Research Centre, Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge Metabolic Research Laboratories (G.S.Y.), Institute of Metabolic Science, Addenbrooke's Hospital, and Human Research Tissue Bank (W.Z.), Cambridge University Hospitals Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Medicine (E.A.B.A.), Faculty of Medicine, The National University of Malaysia Medical Centre, Kuala Lumpur 56000, Malaysia; and Medical Research Council Cancer Unit (G.M.), University of Cambridge, Cambridge CB2 0XZ, United Kingdom.
Wanfeng ZhaoClinical Pharmacology Unit (L.H.S., J.Z., A.E.D.T., S.G., J.J.M., E.A.B.A., A.P.D., M.J.B.) and Cardiovascular Division (N.F., H.Y., M.R.B.), Department of Medicine, University of Cambridge, Cambridge National Institute for Health Research (S.G.N.), Biomedical Research Centre, Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge Metabolic Research Laboratories (G.S.Y.), Institute of Metabolic Science, Addenbrooke's Hospital, and Human Research Tissue Bank (W.Z.), Cambridge University Hospitals Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Medicine (E.A.B.A.), Faculty of Medicine, The National University of Malaysia Medical Centre, Kuala Lumpur 56000, Malaysia; and Medical Research Council Cancer Unit (G.M.), University of Cambridge, Cambridge CB2 0XZ, United Kingdom.
Martin R BennettClinical Pharmacology Unit (L.H.S., J.Z., A.E.D.T., S.G., J.J.M., E.A.B.A., A.P.D., M.J.B.) and Cardiovascular Division (N.F., H.Y., M.R.B.), Department of Medicine, University of Cambridge, Cambridge National Institute for Health Research (S.G.N.), Biomedical Research Centre, Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge Metabolic Research Laboratories (G.S.Y.), Institute of Metabolic Science, Addenbrooke's Hospital, and Human Research Tissue Bank (W.Z.), Cambridge University Hospitals Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Medicine (E.A.B.A.), Faculty of Medicine, The National University of Malaysia Medical Centre, Kuala Lumpur 56000, Malaysia; and Medical Research Council Cancer Unit (G.M.), University of Cambridge, Cambridge CB2 0XZ, United Kingdom.
Elena A B AzizanClinical Pharmacology Unit (L.H.S., J.Z., A.E.D.T., S.G., J.J.M., E.A.B.A., A.P.D., M.J.B.) and Cardiovascular Division (N.F., H.Y., M.R.B.), Department of Medicine, University of Cambridge, Cambridge National Institute for Health Research (S.G.N.), Biomedical Research Centre, Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge Metabolic Research Laboratories (G.S.Y.), Institute of Metabolic Science, Addenbrooke's Hospital, and Human Research Tissue Bank (W.Z.), Cambridge University Hospitals Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Medicine (E.A.B.A.), Faculty of Medicine, The National University of Malaysia Medical Centre, Kuala Lumpur 56000, Malaysia; and Medical Research Council Cancer Unit (G.M.), University of Cambridge, Cambridge CB2 0XZ, United Kingdom.
Anthony P DavenportClinical Pharmacology Unit (L.H.S., J.Z., A.E.D.T., S.G., J.J.M., E.A.B.A., A.P.D., M.J.B.) and Cardiovascular Division (N.F., H.Y., M.R.B.), Department of Medicine, University of Cambridge, Cambridge National Institute for Health Research (S.G.N.), Biomedical Research Centre, Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge Metabolic Research Laboratories (G.S.Y.), Institute of Metabolic Science, Addenbrooke's Hospital, and Human Research Tissue Bank (W.Z.), Cambridge University Hospitals Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Medicine (E.A.B.A.), Faculty of Medicine, The National University of Malaysia Medical Centre, Kuala Lumpur 56000, Malaysia; and Medical Research Council Cancer Unit (G.M.), University of Cambridge, Cambridge CB2 0XZ, United Kingdom.
Grahame McKenzieClinical Pharmacology Unit (L.H.S., J.Z., A.E.D.T., S.G., J.J.M., E.A.B.A., A.P.D., M.J.B.) and Cardiovascular Division (N.F., H.Y., M.R.B.), Department of Medicine, University of Cambridge, Cambridge National Institute for Health Research (S.G.N.), Biomedical Research Centre, Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge Metabolic Research Laboratories (G.S.Y.), Institute of Metabolic Science, Addenbrooke's Hospital, and Human Research Tissue Bank (W.Z.), Cambridge University Hospitals Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Medicine (E.A.B.A.), Faculty of Medicine, The National University of Malaysia Medical Centre, Kuala Lumpur 56000, Malaysia; and Medical Research Council Cancer Unit (G.M.), University of Cambridge, Cambridge CB2 0XZ, United Kingdom.
Morris J BrownClinical Pharmacology Unit (L.H.S., J.Z., A.E.D.T., S.G., J.J.M., E.A.B.A., A.P.D., M.J.B.) and Cardiovascular Division (N.F., H.Y., M.R.B.), Department of Medicine, University of Cambridge, Cambridge National Institute for Health Research (S.G.N.), Biomedical Research Centre, Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge Metabolic Research Laboratories (G.S.Y.), Institute of Metabolic Science, Addenbrooke's Hospital, and Human Research Tissue Bank (W.Z.), Cambridge University Hospitals Foundation Trust, Addenbrooke's Hospital, Cambridge CB2 0QQ, United Kingdom; Department of Medicine (E.A.B.A.), Faculty of Medicine, The National University of Malaysia Medical Centre, Kuala Lumpur 56000, Malaysia; and Medical Research Council Cancer Unit (G.M.), University of Cambridge, Cambridge CB2 0XZ, United Kingdom.
National Institute for Health Research · GB
Funding
British Heart Foundation FS/11/35/28871British Heart Foundation FS/12/33/29561British Heart Foundation FS/12/8/29377British Heart Foundation FS/14/12/30540British Heart Foundation FS/14/75/31134British Heart Foundation PG/07/085/23349British Heart Foundation RG/13/14/30314British Heart Foundation SP/08/002/24118Medical Research Council G0800784Medical Research Council G1000847Medical Research Council MC_UU_12012/5Wellcome TrustWellcome Trust 085686/Z/08/A
Abstract
contextAldosterone synthesis and cellularity in the human adrenal zona glomerulosa (ZG) is sparse and patchy, presumably due to salt excess. The frequency of somatic mutations causing aldosterone-producing adenomas (APAs) may be a consequence of protection from cell loss by constitutive aldosterone production.
objectiveThe objective of the study was to delineate a process in human ZG, which may regulate both aldosterone production and cell turnover.
designThis study included a comparison of 20 pairs of ZG and zona fasciculata transcriptomes from adrenals adjacent to an APA (n = 13) or a pheochromocytoma (n = 7).
interventionsInterventions included an overexpression of the top ZG gene (LGR5) or stimulation by its ligand (R-spondin-3).
main outcome measuresA transcriptome profile of ZG and zona fasciculata and aldosterone production, cell kinetic measurements, and Wnt signaling activity of LGR5 transfected or R-spondin-3-stimulated cells were measured.
resultsLGR5 was the top gene up-regulated in ZG (25-fold). The gene for its cognate ligand R-spondin-3, RSPO3, was 5-fold up-regulated. In total, 18 genes associated with the Wnt pathway were greater than 2-fold up-regulated. ZG selectivity of LGR5, and its absence in most APAs, were confirmed by quantitative PCR and immunohistochemistry. Both R-spondin-3 stimulation and LGR5 transfection of human adrenal cells suppressed aldosterone production. There was reduced proliferation and increased apoptosis of transfected cells, and the noncanonical activator protein-1/Jun pathway was stimulated more than the canonical Wnt pathway (3-fold vs 1.3-fold). ZG of adrenal sections stained positive for apoptosis markers.
conclusionLGR5 is the most selectively expressed gene in human ZG and reduces aldosterone production and cell number. Such conditions may favor cells whose somatic mutation reverses aldosterone inhibition and cell loss.
Indexed as
Adrenal GlandsAldosteroneCell CountDown-RegulationGene Expression ProfilingHumansImmunohistochemistryMicroarray AnalysisReceptors, G-Protein-CoupledTumor Cells, CulturedUp-RegulationWnt Signaling PathwayZona FasciculataZona GlomerulosaAldosteroneLGR5 protein, humanReceptors, G-Protein-Coupled
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