Department of Physiology, Oregon Health Sciences University, Portland, Oregon 97201; and The Division of Reproductive Sciences, Oregon Regional Primate Research Center, Beaverton, Oregon 97006.
Mol Cell Neurosci. 1993 Dec;4(6):532-7. doi: 10.1006/mcne.1993.1065.
Androgens bind to specific high-affinity receptors (AR), thereby initiating gene transcription. We investigated the effects of testosterone (T), dihydrotestosterone (DHT), and 17beta-estradiol (E(2)) on AR transcription and binding in prostate, medial basal hypothalamus (MBH), preoptic area (POA), amygdala, hippocampus, and cortex in the rat. Androgen receptor mRNA was measured by a ribonuclease protection assay. Cytosolic and nuclear AR binding (ARc and ARn, respectively) were measured by in vitro binding assays. In the prostate AR mRNA levels were low in intact animals. Castration produced a fourfold elevation of AR mRNA which was reduced to intact values by treatment with T or DHT (P < 0.05; n = 4). E(2) had no effect compared to castrate levels. In contrast to the prostate, no treatment effect was observed on the expression of AR gene in the MBH, POA, amygdala, hippocampus, or cortex. On the premise that treatment effects on AR mRNA in the brain may require longer than 48 h, we treated rats for 4 and 7 days and found no treatment effect on the expression of AR mRNA in MBH, POA, or amygdala. Next, we compared AR binding with its mRNA between prostate and various brain areas. Castration significantly increased ARc and reduced ARn compared to intact levels, and androgen treatments restored both ARc and ARn to intact values in prostate and brain areas (P < 0.05; n = 5). Changes in AR mRNA levels in prostate corresponded to changes in ARc but not ARn in castrated and androgen-treated males, which suggests that ARc is newly synthesized receptor. In contrast, ARc differed quantitatively between prostate and neural tissues. These results show that DHT regulates AR transcription in rat prostate as effectively as T. Our data also suggest that AR gene transcriptional activity in prostate and selected brain areas may be subjected to differential regulatory mechanisms. This may be due to the presence of tissue-specific regulatory proteins.
雄激素与特定的高亲和力受体 (AR) 结合，从而启动基因转录。我们研究了睾酮 (T)、二氢睾酮 (DHT) 和 17β-雌二醇 (E(2)) 对大鼠前列腺、中基底下丘脑 (MBH)、视前区 (POA)、杏仁核、海马和皮质 AR 转录和结合的影响。通过核糖核酸酶保护分析测定雄激素受体 mRNA。通过体外结合测定法测定胞质和核雄激素受体结合 (ARc 和 ARn)。在完整动物中，前列腺中的 AR mRNA 水平较低。阉割导致 AR mRNA 增加四倍，用 T 或 DHT 处理后降至完整值 (P < 0.05；n = 4)。E(2) 与阉割水平相比没有影响。与前列腺相反，MBH、POA、杏仁核、海马或皮质中 AR 基因的表达没有观察到治疗作用。鉴于治疗对大脑中 AR mRNA 的影响可能需要超过 48 小时，我们用 4 天和 7 天治疗大鼠，发现 MBH、POA 或杏仁核中 AR mRNA 的表达没有治疗作用。接下来，我们比较了前列腺和各种脑区之间的 AR 结合与其 mRNA。与完整水平相比，阉割显着增加了 ARc 并减少了 ARn，雄激素处理将 ARc 和 ARn 都恢复到完整值在前列腺和脑区 (P < 0.05；n = 5)。在阉割和雄激素处理的雄性中，前列腺中 AR mRNA 水平的变化与 ARc 的变化相对应，但与 ARn 的变化无关，这表明 ARc 是新合成的受体。相反，ARc 在前列腺和神经组织之间存在数量上的差异。这些结果表明 DHT 像 T 一样有效地调节大鼠前列腺中的 AR 转录。我们的数据还表明，前列腺和选定的脑区中 AR 基因转录活性可能受到不同的调节机制的影响。这可能是由于存在组织特异性调节蛋白。
