Glucocorticoid Receptor Antagonist Administration Prevents Adrenal Gland Atrophy in an ACTH-Independent Cushing’s Syndrome Rat Model
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- Atsushi Yasuda
- Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Kanagawa 259-1193, Japan
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- Toshiro Seki
- Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Kanagawa 259-1193, Japan
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- Yoshie Kametani
- Department of Molecular Life Science, Division of Basic Medical Science, Tokai University School of Medicine, Kanagawa 259-1193, Japan
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- Masahiro Koizumi
- Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Kanagawa 259-1193, Japan
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- Natsumi Kitajima
- Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Kanagawa 259-1193, Japan
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- Masayuki Oki
- Division of General Internal Medicine, Department of Internal Medicine, Tokai University School of Medicine, Kanagawa 259-1193, Japan
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- Masami Seki
- Seirei Numazu Hospital, Shizuoka 410-8555, Japan
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- Takatoshi Kakuta
- Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Kanagawa 259-1193, Japan
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- Masafumi Fukagawa
- Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Tokai University School of Medicine, Kanagawa 259-1193, Japan
説明
<jats:p>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 <jats:italic>CYP11B1</jats:italic> 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.</jats:p>
収録刊行物
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- International Journal of Endocrinology
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International Journal of Endocrinology 2019 1-9, 2019-02-19
Wiley
