ARMC5 mutations are associated with high levels of proliferating cell nuclear antigen and the presence of the serotonin receptor 5HT4R in PMAH nodules
Autor(a) principal: | |
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Data de Publicação: | 2020 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Arquivos de Endocrinologia e Metabolismo (Online) |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972020000400390 |
Resumo: | ABSTRACT Objective To analyze the morphological and functional characteristics of primary macronodular adrenal hyperplasia (PMAH) nodules carrying or not carrying ARMC5 mutations and the consequences of the presence of mutations in terms of the pattern of macronodule composition and functional state. Subjects and methods The analyses were performed by hematoxylin-eosin staining, immunohistochemistry, microdissection of spongiocyte tissue and RT-qPCR of histological sections from 16 patients diagnosed with PMAH with germline (5) or germline/somatic mutations (5) and without mutations (6) in the ARMC5 gene. Results Hyperplastic nodules were predominantly composed of spongiocytes in mutated and nonmutated sections. ARMC5 mRNA expression in spongiocytes was higher in ARMC5-mutated nodules than in ARMC5-nonmutated nodules, and homogenous ARMC5 protein distribution was observed. The presence of arginine-vasopressin receptor (AVP1AR) and ectopic ACTH production were observed in both cell populations regardless of ARMC5 mutations; the numbers of serotonin receptor (5HT4R)- and proliferating cell nuclear antigen (PCNA)-positive cells were higher in macronodules carrying ARMC5 mutations than in those without mutations. Conclusions Our results suggest that the presence of ARMC5 mutations does not interfere with the pattern of distribution of spongiocytes and compact cells or with the presence of AVP1AR, gastric-inhibitory polypeptide receptor (GIPR) and ectopic ACTH. Nevertheless, the higher numbers of PCNA-positive cells in mutated nodules than in nonmutated nodules suggest that mutated ARMC5 can be related to higher proliferation rates in these cells. In conclusion, our results provide more information about the crosstalk among abnormal GPCRs, ectopic ACTH in steroidogenesis and the ARMC5 gene, which may be relevant in understanding the pathogenesis and diagnosis of patients with PMAH. |
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ARMC5 mutations are associated with high levels of proliferating cell nuclear antigen and the presence of the serotonin receptor 5HT4R in PMAH nodulesCushing’s syndromeadrenal hyperplasiaARMC5steroidogenic enzymesaberrant G protein-coupled receptorsectopic ACTHABSTRACT Objective To analyze the morphological and functional characteristics of primary macronodular adrenal hyperplasia (PMAH) nodules carrying or not carrying ARMC5 mutations and the consequences of the presence of mutations in terms of the pattern of macronodule composition and functional state. Subjects and methods The analyses were performed by hematoxylin-eosin staining, immunohistochemistry, microdissection of spongiocyte tissue and RT-qPCR of histological sections from 16 patients diagnosed with PMAH with germline (5) or germline/somatic mutations (5) and without mutations (6) in the ARMC5 gene. Results Hyperplastic nodules were predominantly composed of spongiocytes in mutated and nonmutated sections. ARMC5 mRNA expression in spongiocytes was higher in ARMC5-mutated nodules than in ARMC5-nonmutated nodules, and homogenous ARMC5 protein distribution was observed. The presence of arginine-vasopressin receptor (AVP1AR) and ectopic ACTH production were observed in both cell populations regardless of ARMC5 mutations; the numbers of serotonin receptor (5HT4R)- and proliferating cell nuclear antigen (PCNA)-positive cells were higher in macronodules carrying ARMC5 mutations than in those without mutations. Conclusions Our results suggest that the presence of ARMC5 mutations does not interfere with the pattern of distribution of spongiocytes and compact cells or with the presence of AVP1AR, gastric-inhibitory polypeptide receptor (GIPR) and ectopic ACTH. Nevertheless, the higher numbers of PCNA-positive cells in mutated nodules than in nonmutated nodules suggest that mutated ARMC5 can be related to higher proliferation rates in these cells. In conclusion, our results provide more information about the crosstalk among abnormal GPCRs, ectopic ACTH in steroidogenesis and the ARMC5 gene, which may be relevant in understanding the pathogenesis and diagnosis of patients with PMAH.Sociedade Brasileira de Endocrinologia e Metabologia2020-08-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972020000400390Archives of Endocrinology and Metabolism v.64 n.4 2020reponame:Arquivos de Endocrinologia e Metabolismo (Online)instname:Sociedade Brasileira de Endocrinologia e Metabologia (SBEM)instacron:SBEM10.20945/2359-3997000000236info:eu-repo/semantics/openAccessConceição,Barbara Brito daCavalcante,Isadora PontesKremer,Jean LucasAuricino,Thais BarabbaBento,Eduarda CorrêaZerbini,Maria Claudia NogueiraFragoso,Maria Candida Barisson VillaresLotfi,Claudimara Ferini Paciccoeng2020-10-14T00:00:00Zoai:scielo:S2359-39972020000400390Revistahttps://www.aem-sbem.com/https://old.scielo.br/oai/scielo-oai.php||aem.editorial.office@endocrino.org.br2359-42922359-3997opendoar:2020-10-14T00:00Arquivos de Endocrinologia e Metabolismo (Online) - Sociedade Brasileira de Endocrinologia e Metabologia (SBEM)false |
dc.title.none.fl_str_mv |
ARMC5 mutations are associated with high levels of proliferating cell nuclear antigen and the presence of the serotonin receptor 5HT4R in PMAH nodules |
title |
ARMC5 mutations are associated with high levels of proliferating cell nuclear antigen and the presence of the serotonin receptor 5HT4R in PMAH nodules |
spellingShingle |
ARMC5 mutations are associated with high levels of proliferating cell nuclear antigen and the presence of the serotonin receptor 5HT4R in PMAH nodules Conceição,Barbara Brito da Cushing’s syndrome adrenal hyperplasia ARMC5 steroidogenic enzymes aberrant G protein-coupled receptors ectopic ACTH |
title_short |
ARMC5 mutations are associated with high levels of proliferating cell nuclear antigen and the presence of the serotonin receptor 5HT4R in PMAH nodules |
title_full |
ARMC5 mutations are associated with high levels of proliferating cell nuclear antigen and the presence of the serotonin receptor 5HT4R in PMAH nodules |
title_fullStr |
ARMC5 mutations are associated with high levels of proliferating cell nuclear antigen and the presence of the serotonin receptor 5HT4R in PMAH nodules |
title_full_unstemmed |
ARMC5 mutations are associated with high levels of proliferating cell nuclear antigen and the presence of the serotonin receptor 5HT4R in PMAH nodules |
title_sort |
ARMC5 mutations are associated with high levels of proliferating cell nuclear antigen and the presence of the serotonin receptor 5HT4R in PMAH nodules |
author |
Conceição,Barbara Brito da |
author_facet |
Conceição,Barbara Brito da Cavalcante,Isadora Pontes Kremer,Jean Lucas Auricino,Thais Barabba Bento,Eduarda Corrêa Zerbini,Maria Claudia Nogueira Fragoso,Maria Candida Barisson Villares Lotfi,Claudimara Ferini Pacicco |
author_role |
author |
author2 |
Cavalcante,Isadora Pontes Kremer,Jean Lucas Auricino,Thais Barabba Bento,Eduarda Corrêa Zerbini,Maria Claudia Nogueira Fragoso,Maria Candida Barisson Villares Lotfi,Claudimara Ferini Pacicco |
author2_role |
author author author author author author author |
dc.contributor.author.fl_str_mv |
Conceição,Barbara Brito da Cavalcante,Isadora Pontes Kremer,Jean Lucas Auricino,Thais Barabba Bento,Eduarda Corrêa Zerbini,Maria Claudia Nogueira Fragoso,Maria Candida Barisson Villares Lotfi,Claudimara Ferini Pacicco |
dc.subject.por.fl_str_mv |
Cushing’s syndrome adrenal hyperplasia ARMC5 steroidogenic enzymes aberrant G protein-coupled receptors ectopic ACTH |
topic |
Cushing’s syndrome adrenal hyperplasia ARMC5 steroidogenic enzymes aberrant G protein-coupled receptors ectopic ACTH |
description |
ABSTRACT Objective To analyze the morphological and functional characteristics of primary macronodular adrenal hyperplasia (PMAH) nodules carrying or not carrying ARMC5 mutations and the consequences of the presence of mutations in terms of the pattern of macronodule composition and functional state. Subjects and methods The analyses were performed by hematoxylin-eosin staining, immunohistochemistry, microdissection of spongiocyte tissue and RT-qPCR of histological sections from 16 patients diagnosed with PMAH with germline (5) or germline/somatic mutations (5) and without mutations (6) in the ARMC5 gene. Results Hyperplastic nodules were predominantly composed of spongiocytes in mutated and nonmutated sections. ARMC5 mRNA expression in spongiocytes was higher in ARMC5-mutated nodules than in ARMC5-nonmutated nodules, and homogenous ARMC5 protein distribution was observed. The presence of arginine-vasopressin receptor (AVP1AR) and ectopic ACTH production were observed in both cell populations regardless of ARMC5 mutations; the numbers of serotonin receptor (5HT4R)- and proliferating cell nuclear antigen (PCNA)-positive cells were higher in macronodules carrying ARMC5 mutations than in those without mutations. Conclusions Our results suggest that the presence of ARMC5 mutations does not interfere with the pattern of distribution of spongiocytes and compact cells or with the presence of AVP1AR, gastric-inhibitory polypeptide receptor (GIPR) and ectopic ACTH. Nevertheless, the higher numbers of PCNA-positive cells in mutated nodules than in nonmutated nodules suggest that mutated ARMC5 can be related to higher proliferation rates in these cells. In conclusion, our results provide more information about the crosstalk among abnormal GPCRs, ectopic ACTH in steroidogenesis and the ARMC5 gene, which may be relevant in understanding the pathogenesis and diagnosis of patients with PMAH. |
publishDate |
2020 |
dc.date.none.fl_str_mv |
2020-08-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972020000400390 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972020000400390 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.20945/2359-3997000000236 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Sociedade Brasileira de Endocrinologia e Metabologia |
publisher.none.fl_str_mv |
Sociedade Brasileira de Endocrinologia e Metabologia |
dc.source.none.fl_str_mv |
Archives of Endocrinology and Metabolism v.64 n.4 2020 reponame:Arquivos de Endocrinologia e Metabolismo (Online) instname:Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) instacron:SBEM |
instname_str |
Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) |
instacron_str |
SBEM |
institution |
SBEM |
reponame_str |
Arquivos de Endocrinologia e Metabolismo (Online) |
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Arquivos de Endocrinologia e Metabolismo (Online) |
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Arquivos de Endocrinologia e Metabolismo (Online) - Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) |
repository.mail.fl_str_mv |
||aem.editorial.office@endocrino.org.br |
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1752122517078671360 |