McKenna T M, Woolf P D
Endocrinology. 1985 May;116(5):2003-7. doi: 10.1210/endo-116-5-2003.
A nephrectomized rat model was developed to examine PRL resistance to dopaminergic suppression, which is frequently present in humans with renal insufficiency. The MCR and the response of PRL to a dopamine (DA) infusion (0.4 microgram/kg . min) were measured in 24-h totally nephrectomized (TN) and sham-nephrectomized (SN) rats concurrently treated with alpha-methyl-p-tyrosine (AMPT), an inhibitor of DA synthesis. TN rats became significantly hyperprolactinemic within 1 day [36.2 +/- 7.1 vs. 18.5 +/- 2.5 (+/- SE) ng/ml; P less than 0.05]. SN and TN rats responded to AMPT with significant and sustained 3- and 5.5-fold increases in PRL, which DA reduced by 85% and 24%, respectively. Total nephrectomy decreased the PRL MCR by 58% (TN, 0.51 +/- 0.03; SN, 1.22 +/- 0.13 ml/min; P less than 0.001) and significantly increased the PRL secretion rate (TN, 79 +/- 10; SN, 37 +/- 8 ng/min; P less than 0.01). In the absence of DA infusion, AMPT reduced plasma DA to undetectable levels, while the median eminence DA contents in TN and SN rats were reduced to similar levels. Our data suggest that the totally nephrectomized rat is a suitable model to study PRL resistance to dopaminergic suppression, and that because DA does not cross the blood-brain barrier, the defect in uremia probably occurs at the level of the lactotroph.
为了研究催乳素（PRL）对多巴胺能抑制的抵抗性，建立了肾切除大鼠模型，这种抵抗性在肾功能不全的人类中经常出现。在同时用α-甲基-对-酪氨酸（AMPT，一种多巴胺合成抑制剂）处理的24小时全肾切除（TN）大鼠和假肾切除（SN）大鼠中，测量了PRL的代谢清除率（MCR）以及PRL对多巴胺（DA）输注（0.4微克/千克·分钟）的反应。TN大鼠在1天内血清催乳素显著升高[36.2±7.1对18.5±2.5（±标准误）纳克/毫升；P<0.05]。SN和TN大鼠对AMPT的反应是PRL分别显著且持续增加3倍和5.5倍，DA分别使其降低85%和24%。全肾切除使PRL的MCR降低了58%（TN，0.51±0.03；SN，1.22±0.13毫升/分钟；P<0.001），并显著提高了PRL的分泌率（TN，79±10；SN，37±8纳克/分钟；P<0.01）。在没有DA输注的情况下，AMPT将血浆DA降低到无法检测的水平，而TN和SN大鼠正中隆起的DA含量降低到相似水平。我们的数据表明，全肾切除大鼠是研究PRL对多巴胺能抑制抵抗性的合适模型，并且由于DA不能穿过血脑屏障，尿毒症中的缺陷可能发生在催乳细胞水平。
