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Glucocorticoid Receptor Antagonist Administration Prevents Adrenal Gland Atrophy in an ACTH-Independent Cushing's Syndrome Rat Model
ACTH-independent Cushing's syndrome (CS) is mainly caused by cortisol-secreting adrenocortical tumours. It is well known that secondary adrenal insufficiency occurs after surgical resection of these tumours. In this regard, impaired adrenocortical function is likely induced by atrophy of the re...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399522/ https://www.ncbi.nlm.nih.gov/pubmed/30915117 http://dx.doi.org/10.1155/2019/8708401 |
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author | Yasuda, Atsushi Seki, Toshiro Kametani, Yoshie Koizumi, Masahiro Kitajima, Natsumi Oki, Masayuki Seki, Masami Kakuta, Takatoshi Fukagawa, Masafumi |
author_facet | Yasuda, Atsushi Seki, Toshiro Kametani, Yoshie Koizumi, Masahiro Kitajima, Natsumi Oki, Masayuki Seki, Masami Kakuta, Takatoshi Fukagawa, Masafumi |
author_sort | Yasuda, Atsushi |
collection | PubMed |
description | ACTH-independent Cushing's syndrome (CS) is mainly caused by cortisol-secreting adrenocortical tumours. It is well known that secondary adrenal insufficiency occurs after surgical resection of these tumours. In this regard, impaired adrenocortical function is likely induced by atrophy of the residual adrenal tissue as a result of chronic suppression by the low ACTH levels of the hypercortisolism state. Therefore, we considered the prevention of adrenal atrophy as a method for preventing postoperative adrenal insufficiency. On the basis of these findings, we hypothesized that the use of a glucocorticoid receptor (GR) antagonist before surgery in ACTH-independent CS would rapidly activate the hypothalamic-pituitary-adrenal (HPA) axis and residual adrenal function. We thus examined adrenal function in a dexamethasone- (DEX-) induced CS rat model with or without mifepristone (MIF). In this study, MIF-treated rats had elevated plasma ACTH levels and increased adrenal weights. In addition, we confirmed that there were fewer atrophic changes, as measured by the pathological findings and mRNA expression levels of corticosterone synthase CYP11B1 in the adrenal glands, in MIF-treated rats. These results indicate that MIF treatment prevents the suppression of the HPA axis and the atrophy of the residual adrenal tissue. Therefore, our study suggests that preoperative GR antagonist administration may improve residual adrenal function and prevent postoperative adrenal insufficiency in ACTH-independent CS. |
format | Online Article Text |
id | pubmed-6399522 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-63995222019-03-26 Glucocorticoid Receptor Antagonist Administration Prevents Adrenal Gland Atrophy in an ACTH-Independent Cushing's Syndrome Rat Model Yasuda, Atsushi Seki, Toshiro Kametani, Yoshie Koizumi, Masahiro Kitajima, Natsumi Oki, Masayuki Seki, Masami Kakuta, Takatoshi Fukagawa, Masafumi Int J Endocrinol Research Article ACTH-independent Cushing's syndrome (CS) is mainly caused by cortisol-secreting adrenocortical tumours. It is well known that secondary adrenal insufficiency occurs after surgical resection of these tumours. In this regard, impaired adrenocortical function is likely induced by atrophy of the residual adrenal tissue as a result of chronic suppression by the low ACTH levels of the hypercortisolism state. Therefore, we considered the prevention of adrenal atrophy as a method for preventing postoperative adrenal insufficiency. On the basis of these findings, we hypothesized that the use of a glucocorticoid receptor (GR) antagonist before surgery in ACTH-independent CS would rapidly activate the hypothalamic-pituitary-adrenal (HPA) axis and residual adrenal function. We thus examined adrenal function in a dexamethasone- (DEX-) induced CS rat model with or without mifepristone (MIF). In this study, MIF-treated rats had elevated plasma ACTH levels and increased adrenal weights. In addition, we confirmed that there were fewer atrophic changes, as measured by the pathological findings and mRNA expression levels of corticosterone synthase CYP11B1 in the adrenal glands, in MIF-treated rats. These results indicate that MIF treatment prevents the suppression of the HPA axis and the atrophy of the residual adrenal tissue. Therefore, our study suggests that preoperative GR antagonist administration may improve residual adrenal function and prevent postoperative adrenal insufficiency in ACTH-independent CS. Hindawi 2019-02-19 /pmc/articles/PMC6399522/ /pubmed/30915117 http://dx.doi.org/10.1155/2019/8708401 Text en Copyright © 2019 Atsushi Yasuda et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Yasuda, Atsushi Seki, Toshiro Kametani, Yoshie Koizumi, Masahiro Kitajima, Natsumi Oki, Masayuki Seki, Masami Kakuta, Takatoshi Fukagawa, Masafumi Glucocorticoid Receptor Antagonist Administration Prevents Adrenal Gland Atrophy in an ACTH-Independent Cushing's Syndrome Rat Model |
title | Glucocorticoid Receptor Antagonist Administration Prevents Adrenal Gland Atrophy in an ACTH-Independent Cushing's Syndrome Rat Model |
title_full | Glucocorticoid Receptor Antagonist Administration Prevents Adrenal Gland Atrophy in an ACTH-Independent Cushing's Syndrome Rat Model |
title_fullStr | Glucocorticoid Receptor Antagonist Administration Prevents Adrenal Gland Atrophy in an ACTH-Independent Cushing's Syndrome Rat Model |
title_full_unstemmed | Glucocorticoid Receptor Antagonist Administration Prevents Adrenal Gland Atrophy in an ACTH-Independent Cushing's Syndrome Rat Model |
title_short | Glucocorticoid Receptor Antagonist Administration Prevents Adrenal Gland Atrophy in an ACTH-Independent Cushing's Syndrome Rat Model |
title_sort | glucocorticoid receptor antagonist administration prevents adrenal gland atrophy in an acth-independent cushing's syndrome rat model |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399522/ https://www.ncbi.nlm.nih.gov/pubmed/30915117 http://dx.doi.org/10.1155/2019/8708401 |
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