Effects of estrogen and recombinant human insulin-like growth factor-I on ghrelin secretion in severe undernutrition
Effects of estrogen and recombinant human insulin-like growth factor-I on ghrelin secretion in severe undernutrition
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DOI：
10.1210/jc.2004-0287
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发表时间：
2004-08-01
影响因子：
5.8
通讯作者：
Klibanski, A
中科院分区：
文献类型：
--
作者：
Grinspoon, S;Miller, KK;Klibanski, A
胃饥饿素是一种受营养调节的肠道肽，随着禁食和慢性营养不良而增加，随着食物摄入而减少。慢性营养不良患者的性类固醇水平会发生变化，这可能预示着胃饥饿素的变化。与此同时，慢性营养不良的特点是igf - 1水平低，这也可能直接或通过生长激素轴的变化影响胃饥饿素。在严重营养不良患者中，性类固醇对胃饥饿素的调节以及IGF-I对胃饥饿素的影响尚不清楚。我们研究了78名神经性厌食症女性受试者同时随机接受雌激素（Ovcon 35, 35杯乙炔雌二醇和0.4 mg去甲稀酮）和重组人（rh） IGF-I（30杯/kg sc，每天两次）的性类固醇和IGF-I对胃饥饿素的影响，在2 × 2因子模型中，雌激素(E)和rhIGF-I对胃饥饿素的个体影响可以确定。受试者年龄24.9 +/- 0.7（平均+/- SEM）岁，体重低（体重指数16.7 +/- 0.2 kg/m(2)）。在基线时，ghrelin与体重指数（r = - 0.39, P = 0.0005）和IGF-I （r = - 0.30, P = 0.01）呈负相关。与单独接受E （δ 3.2 +/- 1.9 nmol/l）或对照组（C； rhIGF-I安慰剂和不接受E） （δ 0.4 +/- 2.0 nmol/l）的受试者相比，单独接受rhIGF-I （δ 23.0 +/- 5.8 nmol/l）和rhIGF-I和E （δ 34.9 +/- 6.3 nmol/l）的受试者的IGF-I升高明显更多（多因素方差分析的总体P < 0.0001， rhIGF-I与C相比P < 0.0001， rhIGF-I和E与C相比P < 0.0001）。饥饿激素显著增加更多的超过6个月仅在响应E(三角洲150 + / - 86 pg / ml),独自rhIGF-I(三角洲198 + / - 116 pg / ml),和组合(E和rhIGF-I)(三角洲441 + / - 214 pg / ml)与C相比(δ- 39 + / - 48 pg / ml)(整体由多元方差分析,P = 0.02 E和C P = 0.01, P = 0.04 rhIGF-I vs . C和P = 0.001 rhIGF-I和E和C)。体重、热量摄入和早晨生长激素水平在两组之间没有显著变化，但ghrelin的变化与所有受试者的生长激素变化呈负相关（r = - 0.27, P = 0.03）。我们的数据表明，在严重营养不良的模型中，rhigf - 1和dei分别增加了胃饥饿素水平。这些作用的机制尚不清楚，可能与对胃促生长素的直接作用或生长激素的变化有关。需要进一步的研究来确定rhIGF-I和E在人体生理学中增加胃饥饿素的机制。
Ghrelin is a nutritionally regulated gut peptide that increases with fasting and chronic undernutrition and decreases with food intake. Sex steroid levels change in chronic undernutrition and might signal changes in ghrelin. At the same time, chronic undernutrition is characterized by low IGF-I that might also influence ghrelin, either directly or through changes in the GH axis. Little is known regarding sex steroid regulation of ghrelin and the effects of IGF-I on ghrelin in severe undernutrition. We investigated the effects of sex steroids and IGF-I on ghrelin in 78 female subjects with anorexia nervosa simultaneously randomized to receive estrogen (Ovcon 35, 35 mug ethinyl estradiol, and 0.4 mg norethindrone) as well as recombinant human ( rh) IGF-I ( 30 mug/kg sc twice a day) in a two-by-two factorial model, in which the individual effects of estrogen ( E) and rhIGF-I on ghrelin could be determined. Subjects were 24.9 +/- 0.7 ( mean +/- SEM) yr of age and had low weight ( body mass index, 16.7 +/- 0.2 kg/m(2)). At baseline, ghrelin was inversely correlated with body mass index (r = - 0.39, P = 0.0005) and IGF-I ( r = - 0.30, P = 0.01). IGF-I increased significantly more in subjects receiving rhIGF-I alone ( Delta 23.0 +/- 5.8 nmol/liter) and rhIGF-I and E (Delta 34.9 +/- 6.3 nmol/liter) compared with subjects receiving E alone (Delta - 3.2 +/- 1.9 nmol/ liter) or control ( C; rhIGF-I placebo and no E) ( Delta 0.4 +/- 2.0 nmol/ liter) ( overall P < 0.0001 by multivariate analysis of variance, P < 0.0001 for rhIGF-I vs. C, P < 0.0001 for rhIGF-I and E vs. C). Ghrelin increased significantly more over 6 months in response to E alone ( Delta 150 +/- 86 pg/ml), rhIGF-I alone ( Delta 198 +/- 116 pg/ml), and the combination ( E and rhIGF-I) ( Delta 441 +/- 214 pg/ml) compared with C ( Delta - 39 +/- 48 pg/ml) ( overall P = 0.02 by multivariate analysis of variance, P = 0.01 for E vs. C, P = 0.04 for rhIGF-I vs. C, and P = 0.001 for rhIGF-I and E vs. C). Weight, caloric intake, and morning GH levels did not change significantly between the groups, but the change in ghrelin was inversely related to the change in GH among all subjects ( r = - 0.27, P = 0.03). Our data demonstrate that, in a model of severe undernutrition, rhIGF-I andEindividually increase ghrelin levels. The mechanisms of these effects are unknown and may relate to direct effects on ghrelin or changes in GH. Further studies are needed to determine the mechanisms by which rhIGF-I and E increase ghrelin in human physiology.