Neuroscience Program, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, British Columbia, Canada.
J Neurosci. 2010 Sep 1;30(35):11762-70. doi: 10.1523/JNEUROSCI.2852-10.2010.
Testosterone contributes to sex differences in hypothalamic-pituitary-adrenal (HPA) function in humans and rodents, but the central organization of this regulation remains unclear. The medial preoptic nucleus (MPN) stands out as an important candidate in this regard because it contains androgen receptors and projects to forebrain nuclei integrating cognitive-affective information and regulating HPA responses to homeostatic threat. These include the HPA effector neurons of the paraventricular nucleus (PVN) of the hypothalamus, medial amygdala, and lateral septum. To test the extent to which androgen receptors in the MPN engage these cell groups, we compared in adult male rats the effects of unilateral microimplants of testosterone and the androgen receptor antagonist hydroxyflutamide into the MPN on acute restraint induced activation and/or neuropeptide expression levels. The basic effects of these implants were lateralized to the sides of the nuclei ipsilateral to the implants. Testosterone, but not hydroxyflutamide implants, decreased stress-induced Fos and arginine vasopressin (AVP) heteronuclear RNA expression in the PVN, as well as Fos expression in the lateral septum. In unstressed animals, AVP mRNA expression in the PVN decreased and increased in response to testosterone and hydroxflutamide MPN implants, respectively. The differential influences of these implants on AVP mRNA expression were opposite in the medial amygdala. These results confirm a role for androgen receptors in the MPN to concurrently modulate neuropeptide expression and activational responses in the PVN and its extended circuitries. This suggests that the MPN is capable of bridging converging limbic influences to the HPA axis with changes in gonadal status.
睾酮有助于人类和啮齿动物下丘脑-垂体-肾上腺（HPA）功能的性别差异，但这种调节的中枢组织仍不清楚。 内侧视前核（MPN）作为一个重要的候选者脱颖而出，因为它包含雄激素受体，并投射到整合认知情感信息并调节 HPA 对稳态威胁反应的前脑核。 这些核包括下丘脑室旁核（PVN）、内侧杏仁核和外侧隔核的 HPA 效应神经元。 为了测试 MPN 中的雄激素受体在多大程度上参与这些细胞群，我们比较了成年雄性大鼠单侧微植入睾酮和雄激素受体拮抗剂羟基氟他胺对急性束缚诱导的激活和/或神经肽表达水平的影响。 这些植入物的基本效应偏向于与植入物同侧的核的侧面。 睾酮而不是羟基氟他胺植入物降低了急性应激诱导的 Fos 和精氨酸加压素（AVP）异核 RNA 在 PVN 中的表达，以及在外侧隔核中的 Fos 表达。 在未应激的动物中，PVN 中的 AVP mRNA 表达在应激和羟氟他胺 MPN 植入物的刺激下分别降低和增加。 这些植入物对 AVP mRNA 表达的不同影响在杏仁核内侧相反。 这些结果证实了雄激素受体在 MPN 中的作用，以同时调节神经肽表达和激活反应在 PVN 及其扩展的回路中。 这表明 MPN 能够通过改变性腺状态来弥合边缘影响到 HPA 轴。
