S Grottoli, E Arvat, C Gauna, B Maccagno, J Ramunni, R Giordano, M Maccario, R Deghenghi, E Ghigo
{"title":"阿普唑仑是一种苯二氮卓类药物,在肥胖患者中,它能减弱但不能消除促肾上腺皮质激素和皮质醇对己卡瑞林(一种GHRP)的反应。","authors":"S Grottoli, E Arvat, C Gauna, B Maccagno, J Ramunni, R Giordano, M Maccario, R Deghenghi, E Ghigo","doi":"10.1038/sj.ijo.0801302","DOIUrl":null,"url":null,"abstract":"<p><p>GH secretagogues (GHS) act on specific receptors at the pituitary and hypothalamic level and possess potent GH-releasing activity but also stimulate prolactin (PRL), ACTH and cortisol (F) secretion. However, hyperactivity of the HPA axis in obesity has been reported. The objective of this study was to clarify the endocrine activity of GHS in obesity. In nine obese patients (obese OB), 9 F, age, (34.8 +/- 3.7 y, body mass index (BMI), 35.0 +/- 2.2 kg/m2; WHR, 0.9 +/- 0.02), 14 controls (normal subjects, NS), 14 F, 30.4 +/- 0.9 y, 20.0 +/- 0.4 kg/m2), we studied the ACTH, F and GH responses to hexarelin (HEX, 2.0 microg/kg), a peptidyl GHS, alone and preceded by alprazolam (ALP, 0.02 mg/kg), and a benzodiazepine which has an inhibitory effect on corticotroph secretion. The HEX-induced ACTH response in OB was higher than that in n.s., but this difference did not attain statistical significance. In n.s. the HEX-induced ACTH response was abolished by ALP (P < 0.03) which, however, only blunted that in OB (P < 0.02). The GH response to HEX in OB was lower (P < 0.02) than that in n.s.. ALP blunted the GH response to HEX in n.s. (P < 0.03) while it did not modify that in OB. The GABAergic activation by alprazolam abolishes the ACTH response to hexarelin in normal subjects, while it only blunts that in obese subjects. Moreover, alprazolam blunts the GH response to hexarelin in normal but not in obese subjects. Thus, obese patients show partial refractoriness to the inhibitory effect of alprazolam on both corticotroph and somatotroph function.</p>","PeriodicalId":14227,"journal":{"name":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2000-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1038/sj.ijo.0801302","citationCount":"5","resultStr":"{\"title\":\"Alprazolam, a benzodiazepine, blunts but does not abolish the ACTH and cortisol response to hexarelin, a GHRP, in obese patients.\",\"authors\":\"S Grottoli, E Arvat, C Gauna, B Maccagno, J Ramunni, R Giordano, M Maccario, R Deghenghi, E Ghigo\",\"doi\":\"10.1038/sj.ijo.0801302\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>GH secretagogues (GHS) act on specific receptors at the pituitary and hypothalamic level and possess potent GH-releasing activity but also stimulate prolactin (PRL), ACTH and cortisol (F) secretion. However, hyperactivity of the HPA axis in obesity has been reported. The objective of this study was to clarify the endocrine activity of GHS in obesity. In nine obese patients (obese OB), 9 F, age, (34.8 +/- 3.7 y, body mass index (BMI), 35.0 +/- 2.2 kg/m2; WHR, 0.9 +/- 0.02), 14 controls (normal subjects, NS), 14 F, 30.4 +/- 0.9 y, 20.0 +/- 0.4 kg/m2), we studied the ACTH, F and GH responses to hexarelin (HEX, 2.0 microg/kg), a peptidyl GHS, alone and preceded by alprazolam (ALP, 0.02 mg/kg), and a benzodiazepine which has an inhibitory effect on corticotroph secretion. The HEX-induced ACTH response in OB was higher than that in n.s., but this difference did not attain statistical significance. In n.s. the HEX-induced ACTH response was abolished by ALP (P < 0.03) which, however, only blunted that in OB (P < 0.02). The GH response to HEX in OB was lower (P < 0.02) than that in n.s.. ALP blunted the GH response to HEX in n.s. (P < 0.03) while it did not modify that in OB. The GABAergic activation by alprazolam abolishes the ACTH response to hexarelin in normal subjects, while it only blunts that in obese subjects. Moreover, alprazolam blunts the GH response to hexarelin in normal but not in obese subjects. Thus, obese patients show partial refractoriness to the inhibitory effect of alprazolam on both corticotroph and somatotroph function.</p>\",\"PeriodicalId\":14227,\"journal\":{\"name\":\"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2000-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1038/sj.ijo.0801302\",\"citationCount\":\"5\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1038/sj.ijo.0801302\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1038/sj.ijo.0801302","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Alprazolam, a benzodiazepine, blunts but does not abolish the ACTH and cortisol response to hexarelin, a GHRP, in obese patients.
GH secretagogues (GHS) act on specific receptors at the pituitary and hypothalamic level and possess potent GH-releasing activity but also stimulate prolactin (PRL), ACTH and cortisol (F) secretion. However, hyperactivity of the HPA axis in obesity has been reported. The objective of this study was to clarify the endocrine activity of GHS in obesity. In nine obese patients (obese OB), 9 F, age, (34.8 +/- 3.7 y, body mass index (BMI), 35.0 +/- 2.2 kg/m2; WHR, 0.9 +/- 0.02), 14 controls (normal subjects, NS), 14 F, 30.4 +/- 0.9 y, 20.0 +/- 0.4 kg/m2), we studied the ACTH, F and GH responses to hexarelin (HEX, 2.0 microg/kg), a peptidyl GHS, alone and preceded by alprazolam (ALP, 0.02 mg/kg), and a benzodiazepine which has an inhibitory effect on corticotroph secretion. The HEX-induced ACTH response in OB was higher than that in n.s., but this difference did not attain statistical significance. In n.s. the HEX-induced ACTH response was abolished by ALP (P < 0.03) which, however, only blunted that in OB (P < 0.02). The GH response to HEX in OB was lower (P < 0.02) than that in n.s.. ALP blunted the GH response to HEX in n.s. (P < 0.03) while it did not modify that in OB. The GABAergic activation by alprazolam abolishes the ACTH response to hexarelin in normal subjects, while it only blunts that in obese subjects. Moreover, alprazolam blunts the GH response to hexarelin in normal but not in obese subjects. Thus, obese patients show partial refractoriness to the inhibitory effect of alprazolam on both corticotroph and somatotroph function.