Khan Izhar A, Thomas Peter
The University of Texas at Austin, Marine Science Institute, Port Aransas, TX 78373, USA.
Mar Environ Res. 2006 Jul;62 Suppl:S25-8. doi: 10.1016/j.marenvres.2006.04.029. Epub 2006 Apr 18.
Exposure of Atlantic croaker to Aroclor 1254 has been shown to impair reproductive neuroendocrine function in this species. In addition, we have identified hypothalamic tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin synthesis, as a target of PCB neuroendocrine toxicity. A previous study in rats has implicated di-ortho-substituted non-coplanar PCB congeners in the inhibition of a similar enzyme, tyrosine hydroxylase, which is the rate-limiting enzyme in dopamine synthesis. Therefore, the present study was designed to investigate whether di-ortho-substituted congeners (PCB 47, PCB 153) or a coplanar congener (PCB 77) present in Aroclor 1254 could be responsible for the reproductive impairment observed in croaker exposed to the PCB mixture. Fish were exposed to PCB 47 and PCB 153 in the diet (0, 0.2 and 1.0 mg/kg body weight/day) for 30 days and to PCB 77 (0.01 and 0.1 mg/kg body weight/day) for 15 days. Neither PCB 47 nor PCB 153 altered hypothalamic TPH activity or gonadal growth at doses similar to the effective doses of the Aroclor 1254 mixture. Therefore, these ortho-substituted PCB congeners known to be neurotoxic in mammalian systems are unlikely to contribute to Aroclor 1254-induced reproductive neuroendocrine disruption in croaker. In contrast, PCB 77 significantly inhibited hypothalamic TPH activity and gonadal growth at doses much lower than the effective doses of Aroclor 1254. The results provide the first evidence for PCB congener-specific disruption of reproductive neuroendocrine function in a vertebrate species.
已证明,将大西洋鳎鱼暴露于多氯联苯混合物Aroclor 1254中会损害该物种的生殖神经内分泌功能。此外,我们已确定血清素合成中的限速酶——下丘脑色氨酸羟化酶(TPH)是多氯联苯神经内分泌毒性的一个靶点。先前对大鼠的一项研究表明,邻位二取代非共平面多氯联苯同系物可抑制一种类似的酶——酪氨酸羟化酶,而酪氨酸羟化酶是多巴胺合成中的限速酶。因此,本研究旨在调查Aroclor 1254中存在的邻位二取代同系物(多氯联苯47、多氯联苯153)或共平面同系物(多氯联苯77)是否可能是导致暴露于多氯联苯混合物的鳎鱼出现生殖功能损害的原因。将鱼在饲料中分别暴露于多氯联苯47和多氯联苯153(0、0.2和1.0毫克/千克体重/天)30天,以及暴露于多氯联苯77(0.01和0.1毫克/千克体重/天)15天。在与Aroclor 1254混合物有效剂量相似的剂量下,多氯联苯47和多氯联苯153均未改变下丘脑TPH活性或性腺生长。因此,这些在哺乳动物系统中已知具有神经毒性的邻位取代多氯联苯同系物不太可能导致Aroclor 1254引起的鳎鱼生殖神经内分泌紊乱。相比之下,多氯联苯77在远低于Aroclor 1254有效剂量的情况下,显著抑制了下丘脑TPH活性和性腺生长。这些结果为多氯联苯同系物对脊椎动物物种生殖神经内分泌功能的特异性破坏提供了首个证据。