To explore the interrelationships between the serotoninergic system and the hypothalamic-pituitary-adrenal (HPA) axis in human obesity, we evaluated cortisol and adrenocorticotropic hormone (ACTH) response to synthetic human corticotropin-releasing hormone (hCRH, 1 μg/kg intravenously [IV]) before and after stimulation of the serotoninergic system by dextrofenfluramine (d- FF, 30 mg/d for 3 months) in nine obese women. These responses were compared with a CRH test (1 μg/kg) carried out in nine age-matched normal-weight women. Plasma cortisol of obese subjects did not significantly increase after CRH (peak value 127.1 ± 11.2 ng/mL v 104.1 ± 9.5 ng/mL). This response was lower (P < .005) than in the controls, in whom the basal cortisol value of 120.6 ± 11.8 ng/mL reached a peak value of 221.2 ± 13.4 ng/mL. However, after administration of d-FF, CRH significantly increased (P < .0001) plasma cortisol (peak value 170.6 ± 18.0 ng/mL v 111.5 ± 10.8 ng/mL) and the response was enhanced (P < .05) as compared with that obtained before d-FF. The ACTH levels of our patients showed a small increment after CRH injection (peak value 13.5 ± 1.7 pg/mL v 9.6 ± 1.1 pg/mL), but the hormonal response was lower (P < .005) than in controls (peak value 38.1 ± 5.5 pg/mL v 13.8 ± 0.8 pg/mL). However, after d-FF, CRH induced a significant increment (P < .05) in plasma ACTH at 30 minutes (20.4 ± 3.7 pg/mL v 10.9 ± 0.9 pg/mL) and 45 minutes (18.0 ± 2.6 pg/mL), even though this response was not significantly different from that observed before d-FF administration. In conclusion, we found a blunted pituitary response to CRH in obese subjects, which was improved by serotoninergic stimulation. This finding indicates a reduced serotonin activity in these subjects and shows that the serotoninergic system is also involved in the regulation of the HPA axis function.
Serotoninergic receptor activation by dextrofenfluramine enhances the blunted pituitary-adrenal responsiveness to corticotropin-releasing hormone in obese subjects
BERNINI, GIAMPAOLO;
1992-01-01
Abstract
To explore the interrelationships between the serotoninergic system and the hypothalamic-pituitary-adrenal (HPA) axis in human obesity, we evaluated cortisol and adrenocorticotropic hormone (ACTH) response to synthetic human corticotropin-releasing hormone (hCRH, 1 μg/kg intravenously [IV]) before and after stimulation of the serotoninergic system by dextrofenfluramine (d- FF, 30 mg/d for 3 months) in nine obese women. These responses were compared with a CRH test (1 μg/kg) carried out in nine age-matched normal-weight women. Plasma cortisol of obese subjects did not significantly increase after CRH (peak value 127.1 ± 11.2 ng/mL v 104.1 ± 9.5 ng/mL). This response was lower (P < .005) than in the controls, in whom the basal cortisol value of 120.6 ± 11.8 ng/mL reached a peak value of 221.2 ± 13.4 ng/mL. However, after administration of d-FF, CRH significantly increased (P < .0001) plasma cortisol (peak value 170.6 ± 18.0 ng/mL v 111.5 ± 10.8 ng/mL) and the response was enhanced (P < .05) as compared with that obtained before d-FF. The ACTH levels of our patients showed a small increment after CRH injection (peak value 13.5 ± 1.7 pg/mL v 9.6 ± 1.1 pg/mL), but the hormonal response was lower (P < .005) than in controls (peak value 38.1 ± 5.5 pg/mL v 13.8 ± 0.8 pg/mL). However, after d-FF, CRH induced a significant increment (P < .05) in plasma ACTH at 30 minutes (20.4 ± 3.7 pg/mL v 10.9 ± 0.9 pg/mL) and 45 minutes (18.0 ± 2.6 pg/mL), even though this response was not significantly different from that observed before d-FF administration. In conclusion, we found a blunted pituitary response to CRH in obese subjects, which was improved by serotoninergic stimulation. This finding indicates a reduced serotonin activity in these subjects and shows that the serotoninergic system is also involved in the regulation of the HPA axis function.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
