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Aldosterone-Regulating Receptors and Aldosterone-Driver Somatic Mutations

التفاصيل البيبلوغرافية
العنوان: Aldosterone-Regulating Receptors and Aldosterone-Driver Somatic Mutations
المؤلفون: Jung Soo Lim, Samuel W. Plaska, Juilee Rege, William E. Rainey, Adina F. Turcu
المصدر: Frontiers in Endocrinology, Vol 12 (2021)
Frontiers in Endocrinology
بيانات النشر: Frontiers Media S.A., 2021.
سنة النشر: 2021
مصطلحات موضوعية: 0301 basic medicine, Aldosterone synthase, Male, Angiotensin receptor, adrenal cortex, Endocrinology, Diabetes and Metabolism, Gene mutation, lcsh:Diseases of the endocrine glands. Clinical endocrinology, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Adrenal Glands, Receptor, Original Research, Aldosterone, Adrenal cortex, High-Throughput Nucleotide Sequencing, Steroid 17-alpha-Hydroxylase, Middle Aged, medicine.anatomical_structure, Female, Receptor, Melanocortin, Type 2, psychological phenomena and processes, Adenoma, Adult, medicine.medical_specialty, endocrine system, education, adrenocorticotropic hormone (ACTH), 030209 endocrinology & metabolism, Adrenocorticotropic hormone, Biology, Real-Time Polymerase Chain Reaction, Receptor, Angiotensin, Type 1, 03 medical and health sciences, Young Adult, Adrenocorticotropic Hormone, Internal medicine, mental disorders, medicine, Humans, Aged, primary aldosteronism, aldosterone, lcsh:RC648-665, Membrane Proteins, angiotensin, Angiotensin II, 030104 developmental biology, chemistry, G Protein-Coupled Inwardly-Rectifying Potassium Channels, Receptors, Corticotropin, adrenal, Mutation, biology.protein, Steroid 11-beta-Hydroxylase
الوصف: BackgroundSomatic gene mutations that facilitate inappropriate intracellular calcium entrance have been identified in most aldosterone-producing adenomas (APAs). Studies suggest that angiotensin II and adrenocorticotropic hormone (ACTH) augment aldosterone production from APAs. Little is known, however, regarding possible variations in response to hormonal stimuli between APAs with different aldosterone-driver mutations.ObjectiveTo analyze the transcript expression of type 1 angiotensin II receptors (AGTR1), ACTH receptors (MC2R), and melanocortin 2 receptor accessory protein (MRAP) in APAs with known aldosterone-driver somatic mutations.MethodsRNA was isolated from APAs with mutations in: KCNJ5 (n = 14), ATP1A1 (n = 14), CACNA1D (n = 14), and ATP2B3 (n = 5), and from normal adjacent adrenal tissue (n = 45). Transcript expression of MC2R, MRAP, AGTR1, aldosterone synthase (CYP11B2), 17α-hydroxylase/17,20-lyase (CYP17A1), and 11β-hydroxylase (CYP11B1) were quantified using quantitative RT-PCR and normalized to β-actin.ResultsCompared to adjacent normal adrenal tissue, APAs had higher transcript levels of CYP11B2 (2,216.4 [1,112.0, 2,813.5]-fold, p < 0.001), MC2R (2.88 [2.00, 4.52]-fold, p < 0.001), and AGTR1 (1.80 [1.02, 2.80]-fold, p < 0.001]), and lower transcript levels of MRAP, CYP17A1, and CYP11B1 (0.28–0.36, p < 0.001 for all). MC2R and CYP11B2 transcripts were lower in APAs with KCNJ5 vs. other mutations (p < 0.01 for both). MC2R expression correlated positively with that of AGTR1 in APAs harboring KCNJ5 and CACNA1D mutations, and with MRAP expression in APAs harboring ATPase mutations.ConclusionsWhile MC2R and AGTR1 are expressed in all APAs, differences were observed based on the underlying aldosterone-driver somatic mutations. In tandem, our findings suggest that APAs with ATPase-mutations are more responsive to ACTH than KCNJ5-mutated APAs.
اللغة: English
تدمد: 1664-2392
الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8c80e97709b133d6615b24fc22ee2803Test
https://www.frontiersin.org/articles/10.3389/fendo.2021.644382/fullTest
حقوق: OPEN
رقم الانضمام: edsair.doi.dedup.....8c80e97709b133d6615b24fc22ee2803
قاعدة البيانات: OpenAIRE
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Array ( [Name] => Abstract [Label] => Description [Group] => Ab [Data] => BackgroundSomatic gene mutations that facilitate inappropriate intracellular calcium entrance have been identified in most aldosterone-producing adenomas (APAs). Studies suggest that angiotensin II and adrenocorticotropic hormone (ACTH) augment aldosterone production from APAs. Little is known, however, regarding possible variations in response to hormonal stimuli between APAs with different aldosterone-driver mutations.ObjectiveTo analyze the transcript expression of type 1 angiotensin II receptors (AGTR1), ACTH receptors (MC2R), and melanocortin 2 receptor accessory protein (MRAP) in APAs with known aldosterone-driver somatic mutations.MethodsRNA was isolated from APAs with mutations in: KCNJ5 (n = 14), ATP1A1 (n = 14), CACNA1D (n = 14), and ATP2B3 (n = 5), and from normal adjacent adrenal tissue (n = 45). Transcript expression of MC2R, MRAP, AGTR1, aldosterone synthase (CYP11B2), 17α-hydroxylase/17,20-lyase (CYP17A1), and 11β-hydroxylase (CYP11B1) were quantified using quantitative RT-PCR and normalized to β-actin.ResultsCompared to adjacent normal adrenal tissue, APAs had higher transcript levels of CYP11B2 (2,216.4 [1,112.0, 2,813.5]-fold, p &lt; 0.001), MC2R (2.88 [2.00, 4.52]-fold, p &lt; 0.001), and AGTR1 (1.80 [1.02, 2.80]-fold, p &lt; 0.001]), and lower transcript levels of MRAP, CYP17A1, and CYP11B1 (0.28–0.36, p &lt; 0.001 for all). MC2R and CYP11B2 transcripts were lower in APAs with KCNJ5 vs. other mutations (p &lt; 0.01 for both). MC2R expression correlated positively with that of AGTR1 in APAs harboring KCNJ5 and CACNA1D mutations, and with MRAP expression in APAs harboring ATPase mutations.ConclusionsWhile MC2R and AGTR1 are expressed in all APAs, differences were observed based on the underlying aldosterone-driver somatic mutations. In tandem, our findings suggest that APAs with ATPase-mutations are more responsive to ACTH than KCNJ5-mutated APAs. )
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