Hypothalamic site of action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
Hypothalamic site of action of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
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2,3,7,8-四氯二苯并-对二恶英 (TCDD) 的下丘脑作用位点。
DOI：
10.1016/0041-008x(88)90290-6
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发表时间：
1988
影响因子：
3.8
通讯作者：
Benson,B
中科院分区：
文献类型：
--
作者：
Russell,DH;Buckley,AR;Shah,GN;Sipes,IG;Blask,DE;Benson,B
与配对对照和未注射对照相比，TCDD在4小时后使大鼠血清泌乳素（PRL）浓度显著降低。多巴胺受体拮抗剂吡莫胺可逆转TCDD的这种作用。这些数据表明，TCDD通过直接影响腺体或改变中隆起（ME）的多巴胺浓度来减少腺垂体PRL的释放。TCDD浓度在5 ~ 500 ng/ml范围内对大鼠腺垂体分泌PRL的能力无直接影响。然而，tcdd治疗大鼠的多巴胺浓度为3.24±0.07 ng / ME，而对照组为2.81±0.08 ng / ME。这是多巴胺浓度的戏剧性变化，因为多巴胺是在门静脉循环中测量的，它表现出快速的周转。大鼠α-甲基-对酪氨酸后多巴胺耗竭速率常数和周转率也显著升高。这些数据提供了TCDD作用于下丘脑部位的第一个生化证据。由于多巴胺抑制垂体腺垂体PRL的释放，因此在TCDD注射后4小时内检测到的血清PRL浓度降低可能是由于ME稳态浓度的增加和这种儿茶酚胺的转化。因此，TCDD的早期作用方式和部位之一是提高结节基底核的多巴胺能活性。TCDD的下丘脑作用部位可能导致暴露于TCDD所产生的许多内分泌效应。
Administration of TCDD produced a significant decrease in the serum concentration of prolactin (PRL) detected in rats after 4 hr compared to pairfed vehicle controls and noninjected controls. This effect of TCDD was reversed by pimozide, a dopamine receptor antagonist. These data suggest that TCDD decreased the release of PRL from the adenohypophysis either by a direct effect on the gland or by altering the dopamine concentration in the median eminence (ME). Concentrations of TCDD from 5 to 500 ng/ml had no direct effect on the ability of the adenohypophysis to secrete PRL in vitro. However, the dopamine concentration increased to 3.24 ± 0.07 ng per ME in TCDD-treated rats compared to 2.81 ± 0.08 ng in vehicle controls. This is a dramatic alteration in the dopamine concentration, since the dopamine is being measured in the portal circulation which exhibits a rapid turnover. The rate constant of dopamine depletion after α-methyl-p-tyrosine and the turnover rate were also significantly elevated in the ME of TCDD-treated rats. These data provide the first biochemical evidence for a hypothalamic site of action of TCDD. Since dopamine is inhibitory to PRL release from the adenohypophysis, increased ME steady-state concentrations and turnover of this catecholamine may be responsible for the decreased concentration of serum PRL detected within 4 hr of TCDD injection. Thus, one of the early modes and sites of action of TCDD is to elevate the dopaminergic activity of the tuberoinfundibular nucleus. A hypothalamic site of action for TCDD may result in a number of the endocrinological effects known to be produced by exposure to TCDD.