Regulation of gonadotropin-releasing hormone (GnRH) secretion by heme molecules: A regulatory role for carbon monoxide?
Regulation of gonadotropin-releasing hormone (GnRH) secretion by heme molecules: A regulatory role for carbon monoxide?
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DOI：
10.1210/en.137.2.790
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发表时间：
1996-02-01
期刊：
影响因子：
4.8
通讯作者：
Brann, DW
中科院分区：
文献类型：
--
作者：
Lamar, CA;Mahesh, VB;Brann, DW
最近的研究表明，包括下丘脑在内的许多大脑区域大量产生的一氧化碳 (CO) 可能具有神经递质的作用。因此，本研究的目的是了解 CO 是否能够调节下丘脑释放因子促性腺激素释放激素 (GnRH) 的分泌。为此，从雌激素引发的切除卵巢的成年大鼠获得内侧基底下丘脑，并在体外孵育1小时预孵育期，然后与媒介物或测试化合物一起孵育30分钟。然后收集培养基用于通过 RIA 测定 GnRH。血红素是一种被血红素加氧酶 (H2O) 裂解产生 CO 的血红素分子，它剂量依赖性地刺激 GnRH 释放，50 μM 是最低有效剂量。血红素的作用并非由于毒性作用，因为所有组在实验结束时都对 KCL 刺激有反应。血红素的作用需要 H2O 裂解，H2O 抑制剂锌原卟啉 IX (ZnPP) 可阻断血红素对 GnRH 释放的作用，这一事实证明了这一点。血红素的作用似乎是由于其转化为二氧化碳，因为二氧化碳清除剂分子血红蛋白完全逆转了血红素的作用。最后，血红素的作用似乎并不是由于另一种 H2O2 产生的产物（胆绿素）的产生，因为胆绿素剂量依赖性地抑制 GnRH 释放。总的来说，目前的研究提供了证据表明 CO 能够调节雌性大鼠下丘脑 GnRH 的释放，表明 CO 可能作为下丘脑中的神经递质发挥作用。
Recent studies suggest that carbon monoxide (CO), which is produced in significant quantities in many brain regions including the hypothalamus, may function as a neurotransmitter. The purpose of the present study therefore was to access whether CO is capable of regulating the secretion of the hypothalamic releasing factor, gonadotropin-releasing hormone (GnRH). To this end, medial basal hypothalami were obtained from estrogen-primed ovariectomized adult rats and incubated in vitro for a 1 hour preincubation period followed by a 30 minute incubation with either vehicle or test compounds. The media was then collected for GnRH determination by RIA. Hematin, a heme molecule cleaved by heme oxygenase (HO) to yield CO, dose-dependently stimulated GnRH release with 50 mu M being the lowest effective dose. The effect of hematin was not due to a toxic effect as all groups responded to KCL stimulation at the end of the experiment. The effect of hematin required HO cleavage as evidenced by the fact that the HO inhibitor, zinc protoporphyrin IX (ZnPP), blocked the effect of hematin on GnRH release. The effect of hematin appeared to be due to its conversion to CO, as the CO scavenger molecule, hemoglobin, completely reversed the effect of hematin. Finally, the effect of hematin did not appear to be due to the generation of the other HO-generated product (biliverdin) since biliverdin dose-dependently inhibited GnRH release. Taken as a whole, the present studies provide evidence that CO is capable of modulating hypothalamic GnRH release in the female rat, suggesting that CO may function as a neurotransmitter in the hypothalamus.