Bian Chen, Zhang Kaiyuan, Zhao Yangang, Guo Qiang, Cai Wenqin, Zhang Jiqiang
Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China.
Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China; Cadet Brigade, Third Military Medical University, Chongqing 400038, China.
Steroids. 2014 Oct;88:7-14. doi: 10.1016/j.steroids.2014.06.006. Epub 2014 Jun 16.
Androgens including testosterone and dihydrotestosterone play important roles on brain structure and function, either directly through androgen receptor or indirectly through estrogen receptors, which need coactivators for their transcription activation. Steroid receptor coactivator-1 (SRC-1) has been shown to be multifunctional potentials in the brain, but how it is regulated by androgens in the brain remains unclear. In this study, we explored the effect of orchidectomy (ORX) on the expression of SRC-1 in the adult male mice using nickel-intensified immunohistochemistry. The results showed that ORX induced dramatic decrease of SRC-1 immunoreactivity in the olfactory tubercle, piriform cortex, ventral pallidum, most parts of the septal area, hippocampus, substantia nigra (compact part), pontine nuclei and nucleus of the trapezoid body (p<0.01). Significant decrease of SRC-1 was noticed in the dorsal and lateral septal nucleus, medial preoptical area, dorsomedial and ventromedial hypothalamic nucleus and superior paraolivary nucleus (p<0.05). Whereas in other regions examined, levels of SRC-1 immunoreactivity were not obviously changed by ORX (p>0.05). The above results demonstrated ORX downregulation of SRC-1 in specific regions that have been involved in sense of smell, learning and memory, cognition, neuroendocrine, reproduction and motor control, indicating that SRC-1 play pivotal role in the mediating circulating androgenic regulation on these important brain functions. It also indicates that SRC-1 may serve as a novel target for the central disorders caused by the age-related decrease of circulating androgens.
包括睾酮和双氢睾酮在内的雄激素对脑结构和功能起着重要作用，它们可直接通过雄激素受体，或间接通过雌激素受体发挥作用，而雌激素受体的转录激活需要共激活因子。类固醇受体共激活因子-1（SRC-1）已被证明在大脑中具有多种功能潜力，但雄激素如何在大脑中对其进行调节仍不清楚。在本研究中，我们使用镍增强免疫组织化学方法，探讨了去势（ORX）对成年雄性小鼠SRC-1表达的影响。结果显示，去势导致嗅结节、梨状皮质、腹侧苍白球、大部分隔区、海马、黑质（致密部）、脑桥核和梯形核中SRC-1免疫反应性显著降低（p<0.01）。在背侧和外侧隔核、内侧视前区、背内侧和腹内侧下丘脑核以及上橄榄旁核中，SRC-1也有显著降低（p<0.05）。而在其他检测区域，去势并未明显改变SRC-1免疫反应性水平（p>0.05）。上述结果表明，去势下调了特定区域的SRC-1，这些区域参与嗅觉、学习和记忆、认知、神经内分泌、生殖及运动控制，这表明SRC-1在介导循环雄激素对这些重要脑功能的调节中起关键作用。这也表明SRC-1可能是由循环雄激素随年龄增长而减少所导致的中枢性疾病的一个新靶点。
