alpha 2-adrenoceptor regulation of the hypothalamic-pituitary-adrenocortical axis in obesity

BACKGROUND Abdominal obesity is associated with hyper-responsiveness of the hypothalamic-pituitary-adrenocortical (HPA) axis to stimulatory neuropepti des and to stress. Catecholamines are involved in the regulation of the HPA axis, particularly during stress, via alpha-adrenoceptor modulation. DESIGN In this study, we investigated the effects of pre-treatment with an alpha 2-adrenoceptor agonist, clonidine (2 mu g/kg over 10 minutes) and ant agonist, yohimbine (0.125 mg/kg bolus, followed by 0.001 mg/kg/minutes per 90 minutes infusion) on the HPA axis, measured by ACTH and cortisol respons e to combined CRH (human, 100 mu g) plus AVP (0.3 IU) administration, and o n noradrenalin (NA) and adrenalin (A) blood levels, in a group of obese wom en with abdominal (A-BFD) or peripheral (P-BFD) body fat distribution and i n nonobese controls. RESULTS During the control CRH + AVP test the ACTH but not the cortisol res ponse was higher (P < 0.05) in obese A-BFD women than in controls, with min or and transient variations of NA levels. Neither the control test nor clon idine or yohimbine influenced basal or post CRH + AVP A concentrations. Clo nidine pretreatment similarly and significantly decreased NA levels in all women and, compared to the control test, marginally influenced the ACTH res ponse to CRH + AVP. Conversely, during yohimbine infusion NA levels steadil y and similarly increased to values more or less double baseline values in all groups. Compared to the control test, however, the ACTH response to the CRH + AVP test performed during yohimbine infusion significantly decreased in the control subjects whereas a tendency to a further increase occurred in the obese groups and, specifically, in the A-BFD group significantly (P < 0.05) more than in the P-BFD group. CONCLUSIONS This study shows that alpha 2-adrenoceptor regulation of the HP A axis is different in obese and nonobese women, particularly in stressed c onditions. We suggest that the abnormal ACTH response to CRH + AVP challeng e with increased noradrenergic tone may represent a specific pathophysiolog ical aspect of the abnormal response to stress or to other specific stimula tory factors in obese women, particularly those with abdominal body fat dis tribution.