Glucocorticoid Receptor Antagonist Administration Prevents Adrenal Gland Atrophy in an ACTH-Independent Cushing’s Syndrome Rat Model

Autor: Atsushi Yasuda, Toshiro Seki, Yoshie Kametani, Masahiro Koizumi, Natsumi Kitajima, Masayuki Oki, Masami Seki, Takatoshi Kakuta, Masafumi Fukagawa
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: International Journal of Endocrinology, Vol 2019 (2019)
Druh dokumentu: article
ISSN: 1687-8337
1687-8345
DOI: 10.1155/2019/8708401
Popis: 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.
Databáze: Directory of Open Access Journals
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