Ghizzoni L, Mastorakos G, Street M E, Mazzardo G, Vottero A, Vanelli M, Bernasconi S
Department of Pediatrics, University of Parma, 43100 Parma, Italy.
J Clin Endocrinol Metab. 2001 Aug;86(8):3729-34. doi: 10.1210/jcem.86.8.7758.
The hormonal regulation of the ob gene and leptin secretion in humans is still unclear. To investigate the interactions among leptin, cortisol, and GH, we analyzed and time-cross-correlated their spontaneous 24-h secretion in 12 short normal prepubertal children of both sexes (6 females and 6 males). Time-cross-correlation analyses demonstrated that leptin and cortisol were correlated in both a negative and positive fashion. The negative correlation, with cortisol leading leptin by 4 and 3 h for boys and girls, respectively, might reflect the stimulatory effect of CRH on the sympathetic system, which inhibits leptin secretion; the positive correlation, with leptin leading cortisol by 6 and 5 h for boys and girls, respectively, might reflect a direct effect of leptin on CRH secretion in the hypophyseal portal system. Time-cross-correlation analyses also showed a strong positive correlation between GH and leptin concentrations, with GH leading leptin by 5 and 2 h for boys and girls, respectively, suggesting a possible direct leptin-releasing effect of GH on adipocytes. We conclude that cross-correlation analyses of 24-h hormone secretions under baseline physiological conditions suggest that the hypothalamic-pituitary-adrenal axis might have a prevailing inhibitory effect on leptin secretion, whereas leptin might exert a positive effect on the hypothalamic-pituitary-adrenal axis. The relation between GH and leptin could be a direct one and characterized prevalently by a positive effect of GH on leptin secretion. Further investigations using different experimental systems are needed to ascertain the validity of these mathematically educed conclusions.
人类中ob基因的激素调节以及瘦素分泌情况仍不清楚。为了研究瘦素、皮质醇和生长激素(GH)之间的相互作用,我们分析了12名青春期前身材矮小的正常儿童(6名女性和6名男性)24小时内它们的自发分泌情况,并进行了时间交叉相关性分析。时间交叉相关性分析表明,瘦素和皮质醇呈正负相关。负相关方面,男孩和女孩中皮质醇分别比瘦素提前4小时和3小时,这可能反映了促肾上腺皮质激素释放激素(CRH)对交感神经系统的刺激作用,该作用抑制瘦素分泌;正相关方面,男孩和女孩中瘦素分别比皮质醇提前6小时和5小时,这可能反映了瘦素对垂体门脉系统中CRH分泌的直接作用。时间交叉相关性分析还显示,GH和瘦素浓度之间存在强正相关,男孩和女孩中GH分别比瘦素提前5小时和2小时,这表明GH可能对脂肪细胞有直接的瘦素释放作用。我们得出结论,在基线生理条件下对24小时激素分泌进行交叉相关性分析表明,下丘脑 - 垂体 - 肾上腺轴可能对瘦素分泌具有主要抑制作用,而瘦素可能对下丘脑 - 垂体 - 肾上腺轴发挥积极作用。GH和瘦素之间的关系可能是直接的,主要表现为GH对瘦素分泌的积极作用。需要使用不同的实验系统进行进一步研究,以确定这些通过数学推导得出的结论的有效性。