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吡啶斯的明可部分恢复正常衰老过程中生长激素(GH)对生长激素释放激素(GHRH)的反应性。

Pyridostigmine partially restores the GH responsiveness to GHRH in normal aging.

作者信息

Ghigo E, Goffi S, Arvat E, Nicolosi M, Procopio M, Bellone J, Imperiale E, Mazza E, Baracchi G, Camanni F

机构信息

Department of Clinical Physiopathology, University of Turin, Italy.

出版信息

Acta Endocrinol (Copenh). 1990 Aug;123(2):169-73. doi: 10.1530/acta.0.1230169.

DOI:10.1530/acta.0.1230169
PMID:2220258
Abstract

In 11 elderly normal subjects and in 17 young healthy subjects we studied the response of plasma growth hormone to GH-releasing hormone (GHRH(29), 1 microgram/kg iv) alone and preceded by pyridostigmine (120 mg orally 60 min before GHRH), a cholinesterase inhibitor likely able to suppress somatostatin release. The GH response to pyridostigmine alone was also examined. Basal plasma GH levels were similar in elderly and young subjects. In the elderly, GHRH induced a GH rise (AUC, median and range: 207.5, 43.5-444.0 micrograms.l-1.h-1) which was lower (p = 0.006) than that observed in young subjects (548.0, 112.5-2313.5 micrograms.l-1.h-1). The pyridostigmine-induced GH rise in the elderly was similar to that in young subjects (300.5, 163.0-470.0 vs 265.0, 33.0-514.5 micrograms.l-1.h-1). Pyridostigmine potentiated the GH responsiveness to GHRH in both elderly (437.5, 152.0-1815.5 micrograms.l-1.h-1; p = 0.01 vs GHRH alone) and young subjects (2140.0, 681.5-4429.5 micrograms.l-1.h-1; p = 0.0001 vs GHRH alone). However, the GH response to pyridostigmine + GHRH was significantly lower (p = 0.0001) in elderly than in young subjects. In conclusion, the cholinergic enhancement by pyridostigmine is able to potentiate the blunted GH response to GHRH in elderly subjects, inducing a GH increase similar to that observed after GHRH alone in young adults. This finding suggests that an alteration of somatostatinergic tone could be involved in the reduced GH secretion in normal aging. However, a decreased GH response to combined administration of pyridostigmine and GHRH in elderly subjects suggests that other abnormalities may coexist, leading to the secretory hypoactivity of somatotropes.

摘要

在11名老年正常受试者和17名年轻健康受试者中,我们研究了血浆生长激素对单独使用生长激素释放激素(GHRH(29),1微克/千克静脉注射)以及在其之前使用吡啶斯的明(在GHRH前60分钟口服120毫克)的反应,吡啶斯的明是一种可能能够抑制生长抑素释放的胆碱酯酶抑制剂。还检测了单独使用吡啶斯的明时的生长激素反应。老年和年轻受试者的基础血浆生长激素水平相似。在老年人中,GHRH诱导生长激素升高(曲线下面积、中位数和范围:207.5,43.5 - 444.0微克·升⁻¹·小时⁻¹),低于年轻受试者(548.0,112.5 - 2313.5微克·升⁻¹·小时⁻¹)(p = 0.006)。老年人中吡啶斯的明诱导的生长激素升高与年轻受试者相似(300.5,163.0 - 470.0与265.0,33.0 - 514.5微克·升⁻¹·小时⁻¹)。吡啶斯的明增强了老年人(437.5,152.0 - 1815.5微克·升⁻¹·小时⁻¹;与单独使用GHRH相比,p = 0.01)和年轻受试者(2140.0,681.5 - 4429.5微克·升⁻¹·小时⁻¹;与单独使用GHRH相比,p = 0.0001)对GHRH的生长激素反应性。然而,老年人中对吡啶斯的明 + GHRH的生长激素反应显著低于年轻受试者(p = 0.0001)。总之,吡啶斯的明引起的胆碱能增强能够增强老年人对GHRH减弱的生长激素反应,诱导的生长激素增加类似于年轻成年人单独使用GHRH后观察到的情况。这一发现表明,生长抑素能张力的改变可能与正常衰老过程中生长激素分泌减少有关。然而,老年人中对吡啶斯的明和GHRH联合给药的生长激素反应降低表明可能存在其他异常,导致生长激素分泌细胞的分泌功能减退。

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引用本文的文献

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Elements in the pathophysiology of diminished growth hormone (GH) secretion in aging humans.
Endocrine. 1997 Aug;7(1):41-8. doi: 10.1007/BF02778061.
2
Arginine enhances the growth hormone-releasing activity of a synthetic hexapeptide (GHRP-6) in elderly but not in young subjects after oral administration.口服后,精氨酸可增强合成六肽(GHRP - 6)在老年受试者中的生长激素释放活性,但在年轻受试者中则不然。
J Endocrinol Invest. 1994 Mar;17(3):157-62. doi: 10.1007/BF03347707.
3
A neuroendocrinological approach to evidence an impairment of central cholinergic function in aging.
J Endocrinol Invest. 1992 Oct;15(9):665-70. doi: 10.1007/BF03345812.