Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC, USA.
J Neuroendocrinol. 2010 Apr;22(4):238-47. doi: 10.1111/j.1365-2826.2010.01965.x. Epub 2010 Jan 27.
Clinical studies show that men are more likely to develop disorders affecting midbrain dopaminergic pathways, such as drug addiction and Parkinson's disease (PD). Although a great deal of focus has been given to the role of oestrogen in the maintenance of midbrain dopaminergic pathways, little is known about how testosterone influences these pathways. In the present study, we used stereological analysis of tyrosine hydroxylase-immunoreactive (TH-IR) cell bodies to determine how testosterone influences the dopaminergic cell bodies of the substantia nigra pars compacta (SNpc) and ventral tegmental area (VTA). Rats and mice were castrated at postnatal day (PN) 60, and these midbrain cell populations were counted on PN 90. One month after castration, TH-IR cell number had increased in the SNpc and VTA of rats and mice. Replacement with testosterone or the non-aromatisable analogue dihydrotestosterone (DHT) in castrated animals reduced TH-IR cell number in the SNpc and VTA in rats. In mice, the decrease of TH-IR cell number with testosterone or DHT replacement was observed only in the SNpc. The apparent increase in TH-IR neurone number after castration is not explained by an increase in TH expression because the number of nondopaminergic cells (TH-immunonegative, TH-IN) did not decrease proportionally after castration. TH-IN cell number did not change after castration or hormone replacement in rat or mouse SNpc or VTA. These findings suggest that testosterone may play a suppressive role in midbrain dopaminergic pathways.
临床研究表明，男性更容易出现影响中脑多巴胺能通路的疾病，如药物成瘾和帕金森病（PD）。尽管人们对雌激素在维持中脑多巴胺能通路中的作用给予了极大的关注，但对于睾丸激素如何影响这些通路知之甚少。在本研究中，我们使用酪氨酸羟化酶免疫反应（TH-IR）细胞体的立体学分析来确定睾丸激素如何影响黑质致密部（SNpc）和腹侧被盖区（VTA）中的多巴胺能细胞体。大鼠和小鼠在出生后第 60 天被去势，这些中脑细胞群在第 90 天进行计数。去势后 1 个月，大鼠和小鼠的 SNpc 和 VTA 中的 TH-IR 细胞数量增加。在去势动物中用睾丸激素或非芳香化类似物二氢睾丸酮（DHT）替代可减少 SNpc 和 VTA 中的 TH-IR 细胞数量。在小鼠中，仅在 SNpc 中观察到用睾丸激素或 DHT 替代后 TH-IR 细胞数量的减少。去势后 TH-IR 神经元数量的明显增加不能用 TH 表达的增加来解释，因为去势后非多巴胺能细胞（TH-免疫阴性，TH-IN）的数量没有成比例地减少。去势或激素替代后，大鼠或小鼠 SNpc 或 VTA 中的 TH-IN 细胞数量没有变化。这些发现表明，睾丸激素可能在中脑多巴胺能通路上发挥抑制作用。
