Authors: V Vicennati L Ceroni L Gagliardi U Pagotto A Gambineri S Genghini R Pasquali
Publish Date: 2014/04/02
Volume: 27, Issue: 6, Pages: 541-547
Abstract
Objective Arginine vasopressin AVP has a central role in the response of the hypothalamicpituitaryadrenal HPA axis to stress conditions A low dose of AVP has been shown to have a modest but significant effect on ACTH response in normal weight subjects The aim of this study was to test the response of the HPA axis in obese subjects in order to assess eventual primary neuroendocrine alterations previously demonstrated by using AVP combined with corticotropin releasing hormone CRH In addition given its central inhibitory action on the HPA axis we investigated whether the suppressive capacity of alprazolam APZ pretreatment on the hormone response to lowdose AVP challenge and daily urinary free cortisol UFC excretion rate may be altered in the presence of obesity Design Fifteen overweight or obese women and eight normalweight controls randomly underwent two lowdose AVP tests 03 UI iv bolus one without AVP test and the other preceded by APZ administration 05 mg at midnight and 05 mg 90 min before the test in the morning at 0830 h APZ/AVP test Blood samples for ACTH and cortisol assay were obtained at baseline and throughout each test The day before each test 24hUFC/ creatinine was also measured Results Basal ACTH levels were similar in the two groups whereas cortisol concentrations were significantly lower in the overweight/obese group Overweight/obese women had higher ACTH and cortisol responses to the AVP tests and significantly greater hormone inhibition after APZ than controls In both groups AVPinduced Δpeak cortisol values before and after APZ pretreatment were significantly correlated Body fat distribution had no effect on the HPA axis response to AVP either before or after APZ Moreover APZ decreased 24hUFC/creatinine values unsignificantly in controls and by approximately 50 in the overweight/obese subjects These changes were unrelated to the cortisol response to the AVP test before and after APZ pretreatment On the other hand percent changes of 24hUFC/creatinine after APZ were negatively related to the body mass index BMI but positively with waist circumference values which indicates that the abdominal obesity phenotype may counteract the 24 hUFC/creatinine that would be expected on the basis of BMI values Conclusions Our data further support the concept that in women obesity may represent a condition of hyperresponsiveness or hypersensitivity of the HPA axis to neuroendocrine stimuli which appear to be independent of feedback control In addition the data on the inhibiting capacity of APZ on UFC excretion confirm that the alterations of the HPA axis in obesity is particularly evident in the abdominal phenotype
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