Modulation of Cortisol Metabolism during Treatment of Acromegaly Is Independent of Body Composition and Insulin Sensitivity
Modulation of Cortisol Metabolism during Treatment of Acromegaly Is Independent of Body Composition and Insulin Sensitivity
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肢端肥大症治疗期间皮质醇代谢的调节与身体成分和胰岛素敏感性无关
DOI：
10.1159/000077135
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发表时间：
2001
影响因子：
3.2
通讯作者：
J. Monson
中科院分区：
文献类型：
--
作者：
G. Frajese;N. Taylor;P. Jenkins;G. M. Besser;J. Monson
目的：在成人生长激素替代和活动期肢端肥大症中，通过抑制11β-羟基类固醇脱氢酶1(11β-HSD1)的活性，皮质醇-皮质醇转换的设定点向可的松方向移动。此外，脂肪质量和胰岛素都可能调节11β-HSD1，并且都受到GH状态变化的影响。本研究探讨了GH/IGF1在调节皮质醇代谢中的相对直接作用。方法：对6例(平均53岁，42~76岁；男4例，女2例)未经治疗的肢端肥大症患者在用Sandostatin®LAR®(20~30 mg i.m)治疗6个月期间，平行检测总皮质醇/皮质醇转化率(尿11-羟基/11-氧-皮质醇代谢物比率；Fm/Em)、胰岛素敏感性(稳态模型评估；HOMA%S)和脂肪质量(DXA)。每周4次)。除1例患者外，其余患者ACTH储备正常。结果：基线时，皮尔逊相关分析显示血清GH与Fm/Em呈负相关(r=-0.83，p=0.04)，HOMA%S与Fm/Em呈负相关(r=-0.79，p=0.06)，其他模式均不明显。治疗过程中，血清GH由治疗前的9.9±6.4降至3.5±3.1 ng/ml(P<0.0 1)，血清胰岛素样生长因子-1由78 5±2 68降至43 1±15 6 ng/ml(P<0.005)。Fm/Em由0.5 2±0.1增至0.75±0.0 8(p<；0.0 3)，与11β-HSD1活性升高一致。躯干脂肪百分比(33.0±9.0vs.33.0±8.2)和胰岛素敏感性(HOMA%S：37.1±8.6vs.52.8±33.7)无明显变化。结论：活动期肢端肥大症治疗过程中皮质醇代谢的调节依赖于GH/IGF-1状态的改变，而不受个体身体成分或胰岛素敏感性改变的影响。
Objectives: The set point of cortisol-cortisone conversion is shifted in the direction of cortisone by the inhibition of the activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) during adult GH replacement and in active acromegaly. Additionally, both fat mass and insulin may modulate 11β-HSD1 and are both influenced by changes in GH status. This study examined the relative direct contribution of GH/IGF1 in modulating cortisol metabolism. Methods: Overall cortisol/cortisone conversion (ratio of urine 11-hydroxy-/11-oxo-cortisol metabolites; Fm/Em), insulin sensitivity (homeostatic model assessment; HOMA %S) and fat mass (DXA) were examined in parallel in 6 patients (mean age 53 years, range 42–76; 4 males, 2 females) with previously untreated active acromegaly during 6 months of therapy with Sandostatin® LAR® (20–30 mg i.m. 4 weekly). All but 1 patient had normal ACTH reserve. Results: At baseline, Pearson correlation demonstrated an inverse relationship between serum GH (mean of a 5-point day curve) and Fm/Em (r = –0.83, p = 0.04) and a trend towards an inverse relationship between HOMA %S and Fm/Em (r = –0.79, p = 0.06) but no other patterns were evident. During the course of treatment, serum GH decreased from 9.9 ± 6.4 (mean ± SD) to 3.5 ± 3.1 ng/ml (p < 0.01) and serum IGF-1 from 785 ± 268 to 431 ± 156 ng/ml (p < 0.005). Fm/Em increased from 0.52 ± 0.1 to 0.75 ± 0.08 (p < 0.03) consistent with increased 11β-HSD1 activity. There were no significant changes in truncal fat percentage (33.0 ± 9.0 vs. 33.0 ± 8.2) or insulin sensitivity (HOMA %S: 37.1 ± 8.6 vs. 52.8 ± 33.7). Conclusions: Modulation of cortisol metabolism during treatment of active acromegaly is dependent on changes in GH/IGF-1 status and is not influenced by any individual change in body composition or insulin sensitivity.
影响因子：
15.9
作者：
FRIED, SK;RUSSELL, CD;BROLIN, RE
通讯作者：
BROLIN, RE
人类 CYP19（芳香酶）基因序列的表征，该基因介导脂肪基质细胞和胎儿肝细胞中糖皮质激素的调节。
DOI：
10.1210/mend.9.3.7776980
发表时间：
1995
期刊：
Molecular endocrinology (Baltimore, Md.)
影响因子：
--
作者：
Zhao,Y;Mendelson,CR;Simpson,ER
通讯作者：
Simpson,ER