Abdelgadir S E, Roselli C E, Choate J V, Resko J A
Department of Physiology and Pharmacology, School of Medicine, Oregon Health Sciences University, Portland, Oregon 97201-3098, USA.
Biol Reprod. 1999 May;60(5):1251-6. doi: 10.1095/biolreprod60.5.1251.
Because the distribution and hormonal regulation of the androgen receptor (AR) mRNA in brains and pituitaries of adult rhesus monkeys have not been studied, we cloned and sequenced a 329-base pair segment of the 5' coding region of the rhesus AR cDNA. Monkey AR cDNA was 99% identical with the human sequence and 96% homologous with the rat sequence. Using a ribonuclease protection assay, we studied the distribution and regulation of AR mRNA in brains and anterior pituitary glands of three groups of male rhesus monkeys: intact (n = 3), castrated (Cx, n = 4), and Cx treated with testosterone (n = 6). Serum testosterone levels of Cx males treated with testosterone differed significantly (p < 0.05) in the morning but not in the evening hours from those in intact controls. Serum LH concentrations were significantly suppressed (p < 0.05) in both morning and evening serum samples of testosterone-treated males compared to intact controls. We found the highest concentrations of AR mRNA in the medial basal hypothalamus, the bed nucleus of the stria terminalis, the medial preoptic area-anterior hypothalamus, and the lateral dorsomedial hypothalamus. Intermediate amounts were found in the septum and amygdala. Low amounts were found in the hippocampus, cingulate cortex, parietal cortex, and cerebellum. The anterior pituitary gland also contained a large amount of AR mRNA. Surprisingly, neither Cx for 3 wk nor Cx plus testosterone replacement for 3 wk significantly affected AR mRNA in any brain area or in the pituitary gland. The present study demonstrates that the effectiveness of testosterone as a regulator of LH secretion in male monkeys is not related to changes of AR mRNA in the brain or pituitary gland. It appears that AR mRNA in the monkey brain and pituitary gland is not regulated at the transcriptional level by androgen.
由于尚未对成年恒河猴大脑和垂体中雄激素受体（AR）mRNA的分布及激素调节进行研究，我们克隆并测序了恒河猴AR cDNA 5'编码区的一段329个碱基对的片段。猴AR cDNA与人类序列的同源性为99%，与大鼠序列的同源性为96%。我们采用核糖核酸酶保护分析法，研究了三组雄性恒河猴大脑和垂体前叶中AR mRNA的分布及调节情况：完整组（n = 3）、去势组（Cx，n = 4）以及去势后用睾酮处理组（n = 6）。睾酮处理的去势雄性猴子血清睾酮水平在早晨与完整对照组相比有显著差异（p < 0.05），但在傍晚无显著差异。与完整对照组相比，睾酮处理雄性猴子的早晨和傍晚血清样本中促黄体生成素（LH）浓度均显著降低（p < 0.05）。我们发现，内侧基底下丘脑、终纹床核、内侧视前区 - 下丘脑前部以及外侧背内侧下丘脑的AR mRNA浓度最高。在隔区和杏仁核中发现的量中等。在海马体、扣带回皮质、顶叶皮质和小脑中发现的量较少。垂体前叶也含有大量的AR mRNA。令人惊讶的是，3周的去势处理和3周的去势加睾酮替代处理均未对任何脑区或垂体中的AR mRNA产生显著影响。本研究表明，睾酮作为雄性猴子LH分泌调节因子的有效性与大脑或垂体中AR mRNA的变化无关。看来，猴脑和垂体中的AR mRNA在转录水平上不受雄激素调节。
