Department of Psychiatry and Human Behavior, Brown Alpert Medical School and The Miriam Hospital, Providence, RI 02903, United States.
Psychoneuroendocrinology. 2011 Sep;36(8):1226-38. doi: 10.1016/j.psyneuen.2011.02.017. Epub 2011 Apr 13.
Consistent sex differences in regulation of the hypothalamic pituitary adrenocortical (HPA) axis have been shown in animal models and emerge over puberty. However, parallel work in humans is lacking despite implications for elucidating the emergence of sex differences in depression over puberty. We investigated sex differences in HPA response to corticotropin releasing hormone (CRH) challenge over puberty in a carefully screened normative sample.
Participants were 68 healthy children (41% girls), ages 6-16, with no personal or family history of psychiatric disorder. Pubertal maturation was determined by Tanner staging. Following 24h of adaptation, 9-10 plasma cortisol samples were collected over 30-40 min pre-infusion baseline, 1 μg/kg CRH infusion, and 90-180 min post-infusion recovery. Thirty-seven participants completed 2+ CRH challenges allowing inclusion of cross-sectional and longitudinal data in all analyses. The influence of gender and pubertal maturation on parameters of cortisol response to CRH challenge was investigated using nonlinear mixed model methodology.
Girls showed increasing total cortisol output following CRH challenge over puberty, while boys showed little change in total cortisol output over puberty. Increased cortisol output in girls was explained by slower reactivity and recovery rates leading to prolonged time to reach peak cortisol and delayed return to baseline over puberty. Girls also showed increasing baseline cortisol over puberty, while boys showed declining baseline over puberty.
Results reveal subtle normative sex differences in the influence of pubertal maturation on HPA regulation at the pituitary level. This normative shift may tip the balance towards stress response dysregulation in girls at high risk for depression, and may represent one potential mechanism underlying elevated rates of depression among pubescent girls.
在动物模型中已经显示出下丘脑-垂体-肾上腺皮质（HPA）轴的调节存在一致的性别差异，并且这种差异在青春期出现。然而，尽管这对于阐明青春期抑郁性别差异的出现具有重要意义，但在人类中缺乏类似的研究。我们在经过精心筛选的正常样本中研究了 HPA 对促肾上腺皮质激素释放激素（CRH）挑战的反应在青春期的性别差异。
参与者为 68 名健康儿童（41%为女孩），年龄在 6-16 岁之间，没有个人或家族精神疾病史。青春期成熟度通过 Tanner 分期确定。适应 24 小时后，在预输注基线 30-40 分钟内采集 9-10 个血浆皮质醇样本，然后输注 1μg/kg CRH，输注后 90-180 分钟恢复。37 名参与者完成了 2 次以上的 CRH 挑战，所有分析均包括横断面和纵向数据。使用非线性混合模型方法研究了性别和青春期成熟度对 CRH 挑战后皮质醇反应参数的影响。
女孩在青春期后 CRH 挑战后的总皮质醇输出增加，而男孩在青春期后总皮质醇输出几乎没有变化。女孩皮质醇输出增加的原因是反应和恢复速度较慢，导致达到峰值皮质醇的时间延长，青春期后恢复到基线的时间延迟。女孩在青春期时皮质醇基础值也增加，而男孩在青春期时皮质醇基础值下降。
结果揭示了青春期成熟度对垂体水平 HPA 调节的影响方面微妙的正常性别差异。这种正常的变化可能会使高风险抑郁的女孩的应激反应失调，这可能是青春期女孩抑郁发生率升高的一个潜在机制。
