Endocrine Journal
Online ISSN : 1348-4540
Print ISSN : 0918-8959
ISSN-L : 0918-8959
Mineralocorticoids induce polyuria by reducing apical aquaporin-2 expression of the kidney in partial vasopressin deficiency
Junki Kurimoto Hiroshi TakagiTakashi MiyataYohei KawaguchiYuichi HodaiTetsuro TsumuraDaisuke HagiwaraTomoko KobayashiYoshinori YasudaMariko SugiyamaTakeshi OnoueShintaro IwamaHidetaka SugaRyoichi BannoTakeshi KatsukiFumiaki AndoShinichi UchidaHiroshi Arima
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2023 Volume 70 Issue 3 Pages 295-304


The symptoms of diabetes insipidus may be masked by the concurrence of adrenal insufficiency and emerge after the administration of hydrocortisone, occasionally at high doses. To elucidate the mechanism underlying polyuria induced by the administration of high-dose corticosteroids in the deficiency of arginine vasopressin (AVP), we first examined the secretion of AVP in three patients in whom polyuria was observed only after the administration of high-dose corticosteroids. Next, we examined the effects of dexamethasone or aldosterone on water balance in wild-type and familial neurohypophyseal diabetes insipidus (FNDI) model mice. A hypertonic saline test showed that AVP secretion was partially impaired in all patients. In one patient, there were no apparent changes in AVP secretion before and after the administration of high-dose corticosteroids. In FNDI mice, unlike dexamethasone, the administration of aldosterone increased urine volumes and decreased urine osmolality. Immunohistochemical analyses showed that, after the administration of aldosterone in FNDI mice, aquaporin-2 expression was decreased in the apical membrane and increased in the basolateral membrane in the collecting duct. These changes were not observed in wild-type mice. The present data suggest that treatment with mineralocorticoids induces polyuria by reducing aquaporin-2 expression in the apical membrane of the kidney in partial AVP deficiency.

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