Endocrine Abstracts

HPA is negatively regulated by glucocorticoid feed-back at hypothalamic, pituitary and hippocampal level by glucocorticoid (GR) and mineralcorticoid (MR) receptors. MR antagonists impair HPA rhythm after acute administration. The aim of this study was to verify HPA activity and glico-insulinemic profile both basally and after acute administration of potassium canrenoate (CAN), before and after chronic treatment. We evaluated ACTH, cortisol (F) and dehydroepiandosterone (DHEA) levels during placebo and CAN infusion (200 mg bolus followed by 200 mg i.v. over 240 min) in six healthy women (27.2±1.5 years, BMI 21.4±1.4 kg/m²) at baseline and after 21 days CAN treatment (200 mg/die po). Blood samples were taken every 15′ for 240′ starting from 16.00 to 20.00 h, time period in which glucocorticoids preferentially bind MRs. We also evaluated insulin and glucose levels during all the sessions. At baseline, ACTH, F and DHEA showed a progressive decrease, more marked for F. During CAN infusion, ACTH, F and DHEA were significantly higher than during placebo (P<0.05 starting from +15′). After chronic CAN treatment, basal F and DHEA were higher than at baseline (P<0.05 from +30′ to +210′), while ACTH showed a trend but not significant toward increase. Moreover, acute CAN infusion was unable to further increase all the hormonal levels. No differences in insulin and glucose levels were recorded before and after CAN treatment. These findings demonstrate that acute MR antagonism is able to amplify HPA activity during the quiescent phase of the circadian rhythm, in agreement with previously observed at the nadir of the circadian rhythm. Interestingly, chronic MR antagonism up-regulates the HPA activity and makes it refractory to further increase induced by acute CAN administration. This suggests an alteration in the MR sensitivity after prolonged antagonism leading to a derangement in the MR-mediated glucocorticoid feed-back.