COORDINATE ACTIVATION OF THE CORTICOTROPIC AXIS BY INSULIN-INDUCED HYPOGLYCEMIA - SIMULTANEOUS ESTIMATES OF BETA-ENDORPHIN, ADRENOCORTICOTROPIN AND CORTISOL SECRETION AND DISAPPEARANCE IN NORMAL MEN

被引:36
作者
IRANMANESH, A
LIZARRALDE, G
VELDHUIS, JD
机构
[1] UNIV VIRGINIA,CTR HLTH SCI,DIV ENDOCRINOL & METAB,CHARLOTTESVILLE,VA 22903
[2] UNIV VIRGINIA,CTR HLTH SCI,DEPT MED,CHARLOTTESVILLE,VA 22903
来源
ACTA ENDOCRINOLOGICA | 1993年 / 128卷 / 06期
关键词
D O I
10.1530/acta.0.1280521
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
In the present study, we investigated the coordinate kinetic response of the corticotropic axis to the acute metabolic stress of hypoglycemia by applying deconvolution analysis to adrenocorticotropin (ACTH), beta-endorphin and cortisol concentration-time series generated in seven normal men after intravenous administration of insulin. Hypoglycemic stress resulted in a 22-fold increase in the mean plasma concentration of ACTH to a maximum of 77 +/- 15 pmol/l, in conjunction with a 7.5-fold increase in the mean plasma fl-endorphin concentration, the maximal value of which was 9 6 +/- 11 pmol/l. Plasma cortisol concentrations increased by 2.6-fold with a mean value of 734 +/- 14 nmol/l. Maximal plasma ACTH and beta-endorphin concentrations were preceded by discrete secretory bursts with peak amplitudes of 10.5 +/- 2.7 and 10.6 +/- 2.0 pmol.1(-1).min-1 (20-fold and ninefold increases compared to control), respectively. The mass of ACTH released was 114 +/- 20 pmol/l (3.4-fold increase), which corresponds to a total amount of 1.25 mug (50% of daily production and 0. 5% of reported pituitary stores), assuming a distribution volume of 40 ml/kg. A total amount of 4.4 +/- 0.7 mg of cortisol was released after insulin-induced hypoglycemia, based on a mean cortisol secretory mass of 1088 +/- 137 nmol/I and a presumed 11.3-1 volume of distribution. Deconvolution-based estimates of the endogenous half-lives of ACTH, beta-endorphin and cortisol were 17 +/- 0.6, 22 +/- 1.7 and 65 +/- 5.3 min, respectively. In summary, deconvolution analysis revealed a rapid coordinate activation of ACTH, beta-endorphin and cortisol secretion after hypoglycemic stress, which correlated closely but temporally preceded increases in the respective plasma concentrations. Our inference that only a small fraction of pituitary ACTH content is released during hypoglycemic stress emphasizes the large reserve capability of the pituitary corticotropes. The percentage response of adrenal gland to the metabolic stress of hypoglycemia was of lesser magnitude, possibly owing to the rate-limiting properties of cortisol biosynthesis. We conclude that kinetic responses of the hypothalamic-pituitary-adrenal axis to hypoglycemic stress exhibit exquisite temporal synchrony and manifest a marked reserve capacity.
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页码:521 / 528
页数:8
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