Evidence against a Self-Inhibition of ACTH Secretion in Man
作者:
Francesco Cavagnini,
Cecilia Invitti,
Leila Danesi,
Marco Passamonti,
Roldano Fossati,
期刊:
Neuroendocrinology
(Karger Available online 1985)
卷期:
Volume 41,
issue 6
页码: 518-525
ISSN:0028-3835
年代: 1985
DOI:10.1159/000124229
出版商: S. Karger AG
关键词: ACTH;ACTH1-17;Self-inhibition mechanism;ACTH regulation;ACTH radioimmunoassay
数据来源: Karger
摘要:
To ascertain the physiological relevance of an autoregulation of adrenocorticotropic hormone (ACTH) secretion in man, we studied the effect of alsactide (β-Alai, Lys17-ACTH1-17-4-amino-N-butylamide), a synthetic ACTH analogue with potent steroidogenic activity but not recognized in the endogenous ACTH immunoassay, on plasma ACTH pattern in patients with Addison’s disease. Three experimental models were employed as follows: (a) in 6 patients, whose steroid replacement therapy had been discontinued 36 h previously, we compared the effect of alsactide, administered at two dose levels (10 or 100 µg i.v. as bolus followed by the same dose infused over 2 h, and of placebo, on the plasma ACTH pattern; (b) the previous experiment was repeated in 4 patients in whom cortone replacement therapy was substituted for 3 days with dexamethasone, 0.5–1.5 mg daily p.o., so as to lower plasma ACTH levels to within the high normal range; (c) in 4 patients off therapy for 36 h, we evaluated the ACTH response to synthetic ovine corticotropin-releasing factor, 1 µg/kg body weight injected intravenously, occurring during concomitant administration of alsactide, 100 µg i.v. as bolus plus 100 µg infused over 2 h, or placebo. Compared to placebo, alsactide did not significantly affect the pattern of ACTH under any of the experimental conditions investigated. Collectively, our findings, although they have to be interpreted with caution, do not support the idea that a self-regulation mechanism plays an important role in the control of ACTH secretio
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