| Author | Chaves, Amanda da Silva | |
| Author | Magalhães, Nathalia dos Santos | |
| Author | Insuela, Daniella Bianchi Reis | |
| Author | Martins, Patrícia Machado Rodrigues e Silva | |
| Author | Martins, Marco Aurélio | |
| Author | Carvalho, Vinicius de Frias | |
| Access date | 2024-10-22T19:06:35Z | |
| Available date | 2024-10-22T19:06:35Z | |
| Document date | 2024 | |
| Citation | CHAVES, Amanda da Silva et al. Captopril inhibits the overproduction of proopiomelanocortin and adrenocorticotropic hormone in the pituitary gland of male diabetic mice in close relationship with an increase in glucocorticoid receptor expression. European Journal of Pharmacology, p. 1-24, 11 Oct. 2024. | |
| URI | https://www.arca.fiocruz.br/handle/icict/66679 | |
| Description | Produção científica do Laboratório de Inflamação. | pt_BR |
| Sponsorship | This study was financially supported by Fundação Carlos Chagas de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Conselho Nacional de Desenvolvimento Cientı́fico e Tecnológico (CNPq), Programa de Auxı́lio à Pesquisa (PAPESVI/FIOCRUZ), Programa INOVA FIOCRUZ, and Ministério da Saúde, Brazil. The funding agencies had no role in the study design, data collection, and analysis, decision to publish, or preparation of the manuscript. | |
| Language | eng | en_US |
| Publisher | Elsevier | |
| Rights | restricted access | |
| Subject in Portuguese | Angiotensina II | pt_BR |
| Subject in Portuguese | Captopril | pt_BR |
| Subject in Portuguese | Diabetes | pt_BR |
| Subject in Portuguese | Receptor de glicocorticoide | pt_BR |
| Subject in Portuguese | Eixo HPA | pt_BR |
| Subject in Portuguese | POMC | pt_BR |
| Title | Captopril inhibits the overproduction of proopiomelanocortin and adrenocorticotropic hormone in the pituitary gland of male diabetic mice in close relationship with an increase in glucocorticoid receptor expression | en_US |
| Type | Preprint | |
| Abstract | Prior investigation shows that diabetic patients present hypothalamus-pituitary-adrenal (HPA) axis hyperactivity related to impaired negative feedback. This study investigates the effect of Captopril on the overproduction of adrenocorticotropic hormone (ACTH) and its precursor proopiomelanocortin (POMC) in the pituitary gland of male diabetic mice. Diabetes was induced by intravenous injection of alloxan into fasted Swiss-webster mice, and the animals were treated with Captopril for 14 consecutive days, starting 7 days post-diabetes induction. Plasma corticosterone levels were evaluated by ELISA, while pituitary gland expressions of angiotensin-II type 1 receptor (AT₁), angiotensin-II type 2 receptor (AT₂), ACTH, Bax, Bcl-2, KI-67, POMC, and glucocorticoid receptor (GR) were evaluated using immunohistochemistry or western blot. Diabetic mice showed pituitary gland overexpression of AT₁, without altering AT₂ levels, which were sensitive to Captopril treatment. Furthermore, diabetic mice presented hypercortisolism, along with an increase in the number of corticotroph cells, POMC and ACTH expression, and number of proliferative cells, and a decrease of GR expression in the pituitary gland. In addition, treatment with Captopril reduced systemic corticosterone levels, corticotroph and proliferative cell numbers, and Bcl-2, POMC, and ACTH expression in the pituitary gland of diabetic mice, besides increasing the expression of Bax and GR. In conclusion, these findings show that Captopril is a promising therapy for treating complications associated with HPA axis hyperactivity in diabetic patients, in a mechanism probably related to the downregulation of POMC production in the pituitary gland and subsequent reduction of systemic corticosterone levels. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Centro de Pesquisa, Inovação e Vigilância em Covid-19 e Emergências Sanitárias. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Centro de Pesquisa, Inovação e Vigilância em Covid-19 e Emergências Sanitárias. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Centro de Pesquisa, Inovação e Vigilância em Covid-19 e Emergências Sanitárias. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Centro de Pesquisa, Inovação e Vigilância em Covid-19 e Emergências Sanitárias. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Centro de Pesquisa, Inovação e Vigilância em Covid-19 e Emergências Sanitárias. Rio de Janeiro, RJ, Brasil. | |
| Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Centro de Pesquisa, Inovação e Vigilância em Covid-19 e Emergências Sanitárias. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação. Rio de Janeiro, RJ, Brasil. | |
| Subject | Angiotensin II | en_US |
| Subject | Captopril | en_US |
| Subject | Diabetes | en_US |
| Subject | Glucocorticoid receptor | en_US |
| Subject | HPA axis | en_US |
| Subject | POMC | en_US |
| Peer reviewed | Não | |
| Publication status | Não Publicado | |
| xmlui.metadata.dc.subject.ods | 03 Saúde e Bem-Estar | |
| xmlui.metadata.dc.subject.ods | 09 Indústria, inovação e infraestrutura | |
