ALPHA-2-ADRENERGIC AGONISM ENHANCES THE GROWTH-HORMONE (GH) RESPONSE TO GH-RELEASING HORMONE THROUGH AN INHIBITION OF HYPOTHALAMIC SOMATOSTATIN RELEASE IN NORMAL MEN

被引:58
作者
DEVESA, J [1 ]
ARCE, V [1 ]
LOIS, N [1 ]
TRESGUERRES, JAF [1 ]
LIMA, L [1 ]
机构
[1] UNIV MADRID, FAC MED, DEPT PHYSIOL, MADRID 3, SPAIN
关键词
D O I
10.1210/jcem-71-6-1581
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The purpose of this study was to investigate the precise mechanism by which central α2-adrenergic pathways modulate GH secretion in humans. In 10 normal subjects we compared the pattern of clonidine-induced GH release to that elicited by GH-releasifig hormone (GHRH) given at a time of presumably similar responsiveness of the somatotrope. We also evaluated the effect of stimulation by GHRH (either endogenous, by administration of clonidine, or exogenous) on the GH response to a further exogenous GHRH stimulation. In 2 experiments the administration of clonidine (0.150 mg, orally) at 0 or 60 min was followed by a GHRH [GRF-(1–29); 1 μg/kg, iv] challenge at 180 min. In other experiments subjects received on separate occasions placebo or clonidine at 0 min, followed by GHRH at 60 min and dgain at 180 min. In a further experiment the administration of clonidine at 0 min was followed by 2 GHRH challenges (60 and 180 min later). The administration of clonidine 60 or 120 min, but not 180 min, before the GHRH bolus significantly (P < 0.01) increased the GH responses to this challenge compared to those elicited by GHRH when given after placebo in a period of a similar somatotrope responsiveness. These, in turn, were significantly (P < 0.05) higher than those elicited by clonidine alone. The close relationship between pre-GHRH plasma GH values and GHRH-elicited GH peaks, not observed for clonidine, was lost after pretreatment with this drug. These data indicate that clonidine was able to disrupt the intrinsic hypothalamic-somatotroph rhythm, suggesting that α2-adrenergic pathways have a major inhibitory effect on somatostatin release. Our data also indicate that GH responses to a GHRH bolus administered 120 min after a prior GHRH challenge are dependent on two parameters: the intrinsic hypothalamic-somatotroph rhythm at the time of the second GHRH bolus, and the magnitude of GH secretion elicited by the previous somatotroph stimulation. In summary, α2-adrenergic agonism appears to act primarily in GH control by inhibiting the hypothalamic release of somatostatin, rather than by stimulating GHRH secretion. © 1990 by The Endocrine Society.
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页码:1581 / 1588
页数:8
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