Department of Biology/Integrative Biosciences Program, The University of Akron, Akron, Ohio 44325, USA.
Clin Exp Hypertens. 2011;33(2):124-32. doi: 10.3109/10641963.2010.531840. Epub 2011 Jan 27.
Androgens interact with catecholamines in the central nervous system (CNS) to regulate many physiological processes including blood pressure (BP). To test the hypothesis that testosterone (T) and 5a-dihydrotestosterone (DHT) modulate CNS catecholamines and BP through androgen receptor (AR)-dependent and independent mechanisms, we used the testicular feminized male (Tfm) rat. Females that carry the AR mutation (Tfm mutation) on the X chromosome were bred with spontaneously hypertensive rat (SHR) males. The normal AR male and Tfm offspring were divided into groups: control, castrated, castrated, and T or (DHT) replacement. In both AR normal and Tfm males, BP was reduced by castration, but T restored BP in both groups. In the amygdale, castration decreased dopamine (DA) in both strains and both T and DHT restored it. In the bed nucleus of the stria terminalis castration increased DA which was further increased by DHT and reduced to normal by T in both strains. In the frontal cortex, castration reduced DA content in both strains but only T restored it to normal in SHR but not in Tfm. Brain norepinephrine (NE) content showed a significant strain effect for the preoptic area (POA), but no treatment effect. Although castration did not change NE in the amygdala or POA in either strain, both T and DHT increased NE in the Tfm castrates. Blood pressure was influenced by T manipulation and correlated most significantly with DA content in the amygdala, frontal cortex, and stria terminalis. These data demonstrate an action of androgen on brain catecholamines and BP, which is independent of the classic androgen receptor.
雄激素与中枢神经系统 (CNS) 中的儿茶酚胺相互作用,调节包括血压 (BP) 在内的许多生理过程。为了检验睾酮 (T) 和 5α-二氢睾酮 (DHT) 是否通过雄激素受体 (AR) 依赖和非依赖机制调节中枢儿茶酚胺和血压的假说,我们使用了睾丸女性化雄性 (Tfm) 大鼠。携带 AR 突变 (Tfm 突变) 的雌性与自发性高血压大鼠 (SHR) 雄性交配。正常 AR 雄性和 Tfm 后代被分为以下几组:对照组、去势组、去势+T 或 (DHT) 替代组。在 AR 正常和 Tfm 雄性中,去势降低了血压,但 T 恢复了两组的血压。在杏仁核中,去势降低了两种品系的多巴胺 (DA),而 T 和 DHT 则恢复了 DA。在终纹床核中,去势增加了 DA,DHT 进一步增加了 DA,而 T 在两种品系中都将其降低至正常水平。在额叶皮质中,去势降低了两种品系的 DA 含量,但只有 T 在 SHR 中恢复正常,而在 Tfm 中则没有。脑去甲肾上腺素 (NE) 含量在前脑垂体区 (POA) 表现出显著的品系效应,但无处理效应。尽管去势没有改变两种品系的杏仁核或 POA 中的 NE,但 T 和 DHT 均增加了 Tfm 去势大鼠的 NE。血压受到 T 处理的影响,与杏仁核、额叶皮质和终纹床核中的 DA 含量相关性最显著。这些数据表明雄激素对大脑儿茶酚胺和血压的作用,这与经典的雄激素受体无关。