ARMC5 mutations are associated with high levels of proliferating cell nuclear antigen and the presence of the serotonin receptor 5HT4R in PMAH nodules

Detalhes bibliográficos
Autor(a) principal: Conceição,Barbara Brito da
Data de Publicação: 2020
Outros Autores: 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
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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spelling 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)
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institution SBEM
reponame_str Arquivos de Endocrinologia e Metabolismo (Online)
collection Arquivos de Endocrinologia e Metabolismo (Online)
repository.name.fl_str_mv 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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