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  • Author: Hiroyuki Morita x
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Huiping Ni, Tomoatsu Mune, Hiroyuki Morita, Hisashi Daidoh, Junko Hanafusa, Toshiroh Shibata, Noriyoshi Yamakita and Keigo Yasuda

Ni H, Mune T, Morita H, Daidoh H, Hanafusa J, Shibata T, Yamakita N, Yasuda K. Inhibition of aldosterone turn-off phenomenon following chronic adrenocorticotropin treatment with in vivo administration of antiglucocorticoid and antioxidants in rats. Eur J Endocrinol 1995;133:578–84. ISSN 0804–4643

Chronic adrenocorticotropin (ACTH) treatment in rats leads to a fall in aldosterone secretion (aldosterone turn-off or "aldosterone escape" phenomenon) with a concomitant rise in corticosterone. To elucidate whether ACTH-induced aldosterone suppression is mediated by steroid type II receptor or related to a free-radical effect by over-synthesized corticosterone, we examined the effects of a glucocorticoid antagonist, RU486, and antioxidants dimethyl sulfoxide (DMSO) and vitamin E, on the aldosterone turn-off phenomenon in rats. Each rat received daily for 5 days a different dose of ACTH-Z (5, 10, 20 or 40 μg/100 g body weight) 1 mg RU486/100 g body weight, 100 μl (1.3 mmol) DMSO/100 g body weight or 2 mg vitamin E/100 g body weight with subcutaneous injection. Plasma steroid levels and in vitro release of steroids from the adrenal capsule were measured. The ACTH-Z treatment caused a dose-dependent increase in corticosterone and a decrease in aldosterone in both plasma and adrenal capsule experiments, as well as an increase in adrenal weights. For the following study 5 μg/100 g body weight of ACTH-Z was used. Administration of RU486 alone caused no change in plasma aldosterone level compared to controls, even though the steroid type II receptor was blocked, as evidenced by significant increases in plasma ACTH and corticosterone levels. Concomitant administration of RU486 and ACTH-Z increased both plasma corticosterone and aldosterone levels (p< 0.01) but decreased adrenal capsule corticosterone production (p< 0.05) compared to the rats treated with ACTH-Z alone. Treatment with DMSO alone caused a significant increase in plasma ACTH and corticosterone level (p< 0.05) but no change in plasma aldosterone level or adrenal capsule corticosterone and aldosterone production. The ACTH-induced aldosterone decrease was completely prevented by DMSO administration in both plasma and adrenal capsule experiments (p< 0.01). Vitamin E administration resulted in the elevation of plasma levels of ACTH and corticosterone (p< 0.01 and < 0.05) but not aldosterone, and it also increased adrenal capsule corticosterone production (p< 0.01) but not aldosterone production. By vitamin E administration, the ACTH-induced aldosterone decrease was suppressed almost completely in plasma (p< 0.01) and partially in adrenal capsule experiments (p< 0.01) compared to rats treated with ACTH-Z alone. Our findings suggest that RU486, DMSO and vitamin E inhibit the ACTH-induced aldosterone turn-off phenomenon in plasma, possibly due to the increase in activity of P-450aldo through antioxidant action or a steroid type II receptor blocking action.

Keigo Yasuda, Third Department of Internal Medicine, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu MZ500, Japan

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Noriyoshi Yamakita, Celso E Gomez-Sanchez, Tomoatsu Mune, Hiroyuki Morita, Hisashi Yoshida, Seiji Miyazaki and Keigo Yasuda

Yamakita N, Gomez-Sanchez CE, Mune T, Morita H, Yoshida H, Miyazaki S, Yasuda K. Simultaneous measurement of plasma 18-oxocortisol and 18-hydroxycortisol levels in normal man. Eur J Endocrinol 1994;131:74–9. ISSN 0804–4643

Plasma 18-oxocortisol (18-oxoF) and 18-hydroxycortisol (18-OH-F) were measured in 47 healthy subjects. Plasma 18-oxoF and 18-OH-F in the early morning were 0.827 ± 0.04 nmol/l and 3.29 ± 0.175 nmol/l, respectively. The plasma levels of both steroids correlated with each other and with cortisol, but not with aldosterone. Postural stimulation with or without furosemide administration increased 18-oxoF, 18-OH-F, aldosterone and plasma renin activity (PRA). Two hours after 2 mg of oral dexamethasone administration or after an overnight 2 mg of dexamethasone suppression cortisol, 18-oxoF and 18-OH-F decreased. Cortisol, aldosterone, 18-oxo-F and 18-OH-F increased after the intravenous administration of 250 μg of 1–24 ACTH. Changes in plasma 18-oxo-F and 18-OH-F levels correlated with PRA change during the posture studies and correlated with the change of ACTH during the dexamethasone studies. The ratios of post-/pre-test values of the postural stimulation and dexamethasone suppression in 18-oxoF and 18-OH-F were lower than that of aldosterone. Plasma 18-oxoF and 18-OH-F are more dependent on ACTH than on the reninangiotensin system. The ratio of 18-OH-F/18-oxoF, which is between 4 and 5, remains constant during the various stimulation or suppression maneuvers.

Noriyoshi Yamakita, Department of Internal Medicine, Matsunami General Hospital, Kasamatsu, GifuPrefecture, 501-61 Japan

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Noriyoshi Yamakita, Keigo Yasuda, Nobuyasu Noritake, Leilani B. Mercado-Asis, Hiroshi Murase, Tomoatsu Mune, Hiroyuki Morita and Kiyoshi Miura

Abstract.

The clinical and endocrine characteristics of 12 Japanese patients with dexamethasone-suppressible hyperaldosteronism were compared with those in 49 Japanese patients with primary aldosteronism due to aldosteronoma. The results were as follows: 1. Most of the laboratory data in the two groups were almost the same. 2. The grade of vascular damage in both uncontrolled (3) and well-controlled (9) patients with dexamethasonesuppressible hyperaldosteronism did not correlate with blood pressure response. 3. The responsiveness of plasma aldosterone to exogenous ACTH in 6 patients with dexamethasone-suppressible hyperaldosteronism was not different from that in 9 patients with aldosteronoma. Even in 3 well-controlled patients in the former group, the plasma aldosterone response was as low as in all the 3 patients with small aldosteronomas. 4. In 4 patients with small aldosteronomas, plasma aldosterone was continuously suppressed with daily dexamethasone to the same degree as in dexamethasone-suppressible hyperaldosteronism. 5. The blood pressure, however, did not improve even in the patients with small aldosteronomas. The possible indistinguishable mechanism in dexamethasone-suppressible hyperaldosteronism and primary aldosteronism with small adenomas and the role of unknown hypertensinogenic steroid(s) other than aldosterone in inducing hypertension in dexamethasone-suppressible hyperaldosteronism are discussed.