Bratton G R, Hiney J K, Dees W L
Department of Veterinary Anatomy and Public Health, Texas A&M University, College Station 77843.
Life Sci. 1994;55(8):563-71. doi: 10.1016/0024-3205(94)00482-x.
In the present study, we evaluated the in vitro effects of lead (Pb) on basal and stimulated luteinizing hormone releasing hormone (LHRH) and Prostaglandin E2 (PGE2) secretion. Median eminences (ME) were removed from brains of adult male rats and preincubated for 15 minutes in Krebs-Ringer bicarbonate glucose buffer in an atmosphere of 95% O2-5% CO2. These media were discarded and all MEs were subjected to one of the following experiments. In Experiment 1, all MEs were incubated for 30 minutes in medium only. These media were collected and replaced with medium only (controls) or with medium containing Pb doses ranging from 5 to 20 microM. After this 60-minute incubation, media were collected, then replaced with new medium containing 60 microM norepinephrine (NE), or NE plus each dose of Pb, then incubated for a final 30-minute period. Experiment 2 was conducted as above, except PGE2 (2.8 microM) replaced the NE. In both experiments, the amounts of LHRH released was measured by RIA. In experiment 3, NE was again used for the challenge; however, this time, the amount of PGE2 released was measured by RIA. Results indicate that Pb did not alter basal LHRH release, but compared with controls, significantly blocked NE-induced LHRH release in a dose-related manner. Conversely, Pb had no effect on the PGE2-induced release of LHRH. Additionally, Pb did not alter basal PGE2 release; however, it significantly blocked the NE-induced release of PGE2. Since NE-induced LHRH release is mediated by PGE2, these results support the hypothesis that Pb is capable of altering the hypothalamus and suggest that this effect is due, at least in part, to the diminished PGE2 synthesis/release within the ME, resulting in diminished LHRH secretion.
在本研究中,我们评估了铅(Pb)对基础和刺激状态下促黄体生成激素释放激素(LHRH)以及前列腺素E2(PGE2)分泌的体外作用。从成年雄性大鼠脑中取出正中隆起(ME),并在95% O2 - 5% CO2的气氛中,于 Krebs - Ringer 碳酸氢盐葡萄糖缓冲液中预孵育15分钟。弃去这些培养基,所有正中隆起均进行以下实验之一。在实验1中,所有正中隆起仅在培养基中孵育30分钟。收集这些培养基,并用仅含培养基(对照)或含5至20微摩尔/升铅剂量的培养基替换。在这60分钟的孵育后,收集培养基,然后用含60微摩尔/升去甲肾上腺素(NE)或NE加各剂量铅的新培养基替换,再孵育最后30分钟。实验2的操作与上述相同,只是用PGE2(2.8微摩尔/升)替代了NE。在两个实验中,释放的LHRH量均通过放射免疫分析(RIA)测定。在实验3中,再次使用NE进行刺激;然而,这次通过RIA测定释放的PGE2量。结果表明,铅不会改变基础LHRH的释放,但与对照相比,能以剂量相关的方式显著阻断NE诱导的LHRH释放。相反,铅对PGE2诱导的LHRH释放没有影响。此外,铅不会改变基础PGE2的释放;然而,它能显著阻断NE诱导的PGE2释放。由于NE诱导的LHRH释放是由PGE2介导的,这些结果支持了铅能够改变下丘脑的假说,并表明这种作用至少部分是由于正中隆起内PGE2合成/释放减少,导致LHRH分泌减少。