Department of Psychology, Columbia University, New York, New York 10027, USA.
Endocrinology. 2011 May;152(5):1970-8. doi: 10.1210/en.2010-1398. Epub 2011 Mar 1.
Gonadal hormones can modulate circadian rhythms in rodents and humans, and androgen receptors are highly localized within the core region of the mouse suprachiasmatic nucleus (SCN) brain clock. Although androgens are known to modulate neural plasticity in other CNS compartments, the role of androgens and their receptors on plasticity in the SCN is unexplored. In the present study, we ask whether androgens influence the structure and function of the mouse SCN by examining the effects of gonadectomy (GDX) on the structure of the SCN circuit and its responses to light, including induction of clock genes and behavioral phase shifting. We found that after GDX, glial fibrillary acidic protein increased with concomitant decreases in the expression of the synaptic proteins synaptophysin and postsynaptic density 95. We also found that GDX exerts effects on the molecular and behavioral responses to light that are phase dependent. In late night [circadian time (CT)21], GDX increased light-induced mPer1 but not mPer2 expression compared with intact (INT) controls. In contrast, in early night (CT13.5), GDX decreased light induced mPer2 but had no effect on mPer1. At CT13.5, GDX animals also showed larger phase delays than did INT. Treatment of GDX animals with the nonaromatizable androgen dihydrotestosterone restored glial fibrillary acidic protein, postsynaptic density 95, and synaptophysin in the SCN and reinstated the INT pattern of molecular and behavioral responses to light. Together, the results reveal a role for androgens in regulating circuitry in the mouse SCN, with functional consequences for clock gene expression and behavioral responses to photic phase resetting stimuli.
性腺激素可以调节啮齿动物和人类的昼夜节律，雄激素受体在小鼠视交叉上核（SCN）脑钟的核心区域高度本地化。虽然雄激素已知可以调节中枢神经系统其他部位的神经可塑性，但雄激素及其受体对 SCN 可塑性的作用尚未被探索。在本研究中，我们通过检查去势（GDX）对 SCN 电路结构及其对光的反应的影响，包括时钟基因的诱导和行为相位移动，来询问雄激素是否通过影响 SCN 的结构和功能来调节生物钟。我们发现，去势后，神经胶质纤维酸性蛋白增加，同时突触蛋白突触小体和突触后密度 95 的表达减少。我们还发现，去势对光诱导的分子和行为反应的影响具有相位依赖性。在深夜[生物钟时间（CT）21]，与完整（INT）对照组相比，GDX 增加了光诱导的 mPer1 但不是 mPer2 的表达。相比之下，在清晨（CT13.5），GDX 减少了光诱导的 mPer2，但对 mPer1 没有影响。在 CT13.5 时，GDX 动物也表现出比 INT 动物更大的相位延迟。用非芳香化雄激素二氢睾酮治疗 GDX 动物恢复了 SCN 中的神经胶质纤维酸性蛋白、突触后密度 95 和突触小体，并且恢复了 INT 对光相重置刺激的分子和行为反应模式。总之，这些结果揭示了雄激素在调节小鼠 SCN 电路中的作用，对时钟基因表达和对光相重置刺激的行为反应具有功能后果。
