title: Response of the hypothalamic-pituitary-adrenal axis to small dose arginine-vasopressin and daily urinary free cortisol before and after alprazolam pre-treatment differs in obesity.
abstract: OBJECTIVE
  Arginine vasopressin (AVP) has a central role in the response of the hypothalamic-pituitary-adrenal (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 low-dose AVP challenge and daily urinary free cortisol (UFC) excretion rate may be altered in the presence of obesity.
  
  
  METHODS
  Fifteen overweight or obese women and eight normal-weight controls randomly underwent two low-dose AVP tests (0.3 UI iv bolus), one without (AVP test) and the other preceded by APZ administration (0.5 mg at midnight and 0.5 mg 90 min before the test in the morning at 08:30 h) (APZ/AVP test). Blood samples for ACTH and cortisol assay were obtained at baseline and throughout each test. The day before each test, 24h-UFC/ creatinine was also mea-sured.
  
  
  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, AVP-induced delta-peak cortisol values before and after APZ pre-treatment were significantly correlated. Body fat distribution had no effect on the HPA axis response to AVP either before or after APZ. Moreover, APZ decreased 24h-UFC/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 24h-UFC/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 h-UFC/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.
authors.affiliation: Departement of Internal Medicine, S Orsola-Malpighi Hospital, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Vicennati
authors.forename: L
authors.initials: L
authors.lastname: Ceroni
authors.forename: L
authors.initials: L
authors.lastname: Gagliardi
authors.forename: U
authors.initials: U
authors.lastname: Pagotto
authors.forename: A
authors.initials: A
authors.lastname: Gambineri
authors.forename: S
authors.initials: S
authors.lastname: Genghini
authors.forename: R
authors.initials: R
authors.lastname: Pasquali
mesh_terms: D000328:Adult; D000525:Alprazolam / Q000008:administration & dosage / Q000494:pharmacology*; D001127:Arginine Vasopressin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D018757:GABA Modulators / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000652:urine*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000502:physiology*; D009765:Obesity / Q000503:physiopathology*; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D018757:GABA Modulators; D014662:Vasoconstrictor Agents; D001127:Arginine Vasopressin; D006854:Hydrocortisone; D000525:Alprazolam
references.citation: Psychoneuroendocrinology. 1990;15(1):23-8
references.pmid: 2367614
references.citation: Drugs. 1984 Feb;27(2):132-47
references.pmid: 6141930
references.citation: J Clin Psychol. 1983 Mar;39(2):249-51
references.pmid: 6841626
references.citation: J Clin Endocrinol Metab. 1993 Aug;77(2):341-6
references.pmid: 8393881
references.citation: Metabolism. 1991 Oct;40(10):1088-91
references.pmid: 1658546
references.citation: Obes Rev. 2001 May;2(2):73-86
references.pmid: 12119665
references.citation: Endocrinology. 1989 Nov;125(5):2532-9
references.pmid: 2676486
references.citation: J Clin Endocrinol Metab. 1999 Aug;84(8):2611-5
references.pmid: 10443648
references.citation: J Endocrinol Invest. 2002 Sep;25(8):735-47
references.pmid: 12240908
references.citation: Biol Psychiatry. 1992 Nov 15;32(10 ):880-90
references.pmid: 1334713
references.citation: Clin Endocrinol (Oxf). 1998 May;48(5):603-12
references.pmid: 9666872
references.citation: J Biol Chem. 1987 Jan 25;262(3):1129-36
references.pmid: 2433273
references.citation: Endocrinology. 1991 Jan;128(1):197-203
references.pmid: 1846097
references.citation: Acta Med Scand Suppl. 1988;723:71-8
references.pmid: 3164976
references.citation: Neuropsychobiology. 1990-1991;23(3):124-8
references.pmid: 2098668
references.citation: Endocr Rev. 1992 Aug;13(3):453-75
references.pmid: 1330506
references.citation: J Clin Psychiatry. 1983 Aug;44(8 Pt 2):45-7
references.pmid: 6135693
references.citation: J Clin Endocrinol Metab. 1990 May;70(5):1462-71
references.pmid: 2159487
references.citation: J Biochem. 1989 Dec;106(6):1026-9
references.pmid: 2560776
references.citation: Endocr Rev. 1992 May;13(2):164-91
references.pmid: 1319897
references.citation: J Endocrinol Invest. 1999 Jun;22(6):465-71
references.pmid: 10435857
references.citation: J Clin Endocrinol Metab. 1998 Jun;83(6):1853-9
references.pmid: 9626108
references.citation: J Clin Invest. 1990 Jun;85(6):1716-21
references.pmid: 2161426
references.citation: Horm Metab Res. 2000 Nov-Dec;32(11-12):521-5
references.pmid: 11246819
references.citation: J Clin Endocrinol Metab. 2000 Nov;85(11):4093-8
references.pmid: 11095438
references.citation: Growth Horm IGF Res. 2001 Jun;11 Suppl A:S91-5
references.pmid: 11527096
references.citation: J Clin Invest. 1984 Feb;73(2):533-8
references.pmid: 6321557
references.citation: J Clin Endocrinol Metab. 2002 Jan;87(1):166-75
references.pmid: 11788642
references.citation: Respir Med. 1999 Jan;93(1):1-7
references.pmid: 10464840
references.citation: J Clin Endocrinol Metab. 1994 Jul;79(1):140-4
references.pmid: 8027217
references.citation: Endocr Rev. 1993 Apr;14(2):222-40
references.pmid: 8391980
references.citation: J Neuroendocrinol. 1991 Feb 1;3(1):1-9
references.pmid: 19215439
references.citation: Metabolism. 1996 Mar;45(3):351-6
references.pmid: 8606643