In vitro effect of delta 9-tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E2.
In vitro effect of delta 9-tetrahydrocannabinol to stimulate somatostatin release and block that of luteinizing hormone-releasing hormone by suppression of the release of prostaglandin E2.
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δ 9-四氢大麻酚的体外作用是刺激生长抑素释放，并通过抑制前列腺素 E2 的释放来阻断黄体生成素释放激素的释放。
DOI：
10.1073/pnas.87.24.10063
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发表时间：
1990
影响因子：
11.1
通讯作者：
McCann,SM
中科院分区：
文献类型：
--
作者：
Rettori,V;Aguila,MC;Gimeno,MF;Franchi,AM;McCann,SM
以往的体内研究表明，大麻中的主要活性成分四氢大麻酚(THC)注射到清醒雄性大鼠的第三脑室后，可抑制黄体生成素(LH)和生长激素(GH)的分泌。目前的研究旨在确定这些影响的机制。不同剂量的THC分别与茎正中隆起(MES)或下丘脑中底内侧(MBH)片段孵育。THC(10 NM)对体外培养的MES基础促黄体生成素释放激素(LHRH)无明显影响，但可完全阻断多巴胺或去甲肾上腺素对LHRH释放的刺激作用。阻断LHRH释放的有效剂量与阻断MBH体外合成和释放前列腺素E(PGE{sub2})有关。与THC对LHRH释放的抑制作用相反，MES对生长抑素的释放呈剂量相关的促进作用，最小有效剂量为1 nM。由于PGE{sub2}抑制生长抑素的释放，这种促进作用可能还与THC抑制PGE{sub2}的合成和释放有关。作者推测，这些作用是由最近在组织中发现的THC受体介导的。结果表明，THC对促黄体生成素释放的抑制作用是通过阻断LHRH的释放而实现的，而化合物对生长激素的抑制作用至少部分是通过刺激生长抑素的释放来实现的。
Previous in vivo studies have shown that {Delta}{sup 9}-tetrahydrocannabinol (THC), the principal active ingredient in marijuana, can suppress both luteinizing hormone (LH) and growth hormone (GH) secretion after its injection into the third ventricle of conscious male rats. The present studies were deigned to determine the mechanism of these effects. Various doses of THC were incubated with either stalk median eminence fragments (MEs) or mediobasal hypothalamic (MBH) fragments in vitro. Although THC (10 nM) did not alter basal release of LH-releasing hormone (LHRH) from MEs in vitro, it completely blocked the stimulatory action of dopamine or nonrepinephrine on LHRH release. The effective doses to block LHRH release were associated with a blockade of synthesis and release of prostaglandin E{sub 2} (PGE{sub 2}) from MBH in vitro. In contrast to the suppressive effect of THC on LHRH release, somatostatin release from MEs was enhanced in a dose-related manner with a minimal effective dose of 1 nM. Since PGE{sub 2} suppresses somatostatin release, this enhancement may also be related to the suppressive effect of THC on PGE{sub 2} synthesis and release. The authors speculate that these actions are mediated by the recently discovered THC receptors in the tissue. The results indicate that the suppressive effect of THC on LH release is mediated by a blockade of LHRH release, whereas the suppressive effect of the compound on growth hormone release is mediated, at least in part, by a stimulation of somatostatin release.