Participation of the Endocannabinoid System in the Effect of TNF‐α on Hypothalamic Release of Gonadotropin‐Releasing Hormone
Participation of the Endocannabinoid System in the Effect of TNF‐α on Hypothalamic Release of Gonadotropin‐Releasing Hormone
复制标题
内源性大麻素系统参与 TNF-α 对下丘脑促性腺激素释放激素释放的影响
DOI：
10.1196/annals.1366.008
复制
发表时间：
2006
影响因子：
5.2
通讯作者：
V. Rettori
中科院分区：
文献类型：
--
作者：
J. Fernández;J. Prestifilippo;S. Bornstein;S. Mccann;V. Rettori
翻译后摘要：据了解，Δ9-四氢大麻酚（THC），大麻的主要活性成分，可以抑制生殖功能。 此外，我们以前报道过内源性大麻素，大麻素（AEA），抑制促性腺激素释放激素（LHRH）释放从内侧基底下丘脑（MBH）的雄性大鼠在体外孵育，以及降低血浆LH水平后i. c. v. AEA注射到大脑侧脑室。另一方面，已知在内毒素血症期间，下丘脑促性腺激素轴被抑制。因此，本研究的目的是确定TNF-α（一种由脂多糖（LPS）诱导的抑制LHRH释放的促炎细胞因子）的作用是否由内源性大麻素系统的激活介导。腹腔内注射LPS（5 mg/kg）以及i. c. v.注射肿瘤坏死因子-α（TNF-α）（100 ng/大鼠）显著增加处理后3 h取出的MBH中离体测量的AEA合成。为了研究TNF-α也通过增加AEA的合成来发挥作用的可能性，AEA被释放并激活CB 1-r，然后抑制LHRH的释放，我们测量了TNF-α对体外孵育的MBH中AEA合酶活性的影响。正如预期的那样，我们发现TNF-α（2.9 × 10−9 M）增加了AEA的合成。其次，我们发现TNF-α显著降低了毛喉素刺激的LHRH释放，而CB 1-r拮抗剂AM 251（10 - 5 M）阻断了这种抑制作用，支持TNF-α抑制LHRH释放的假设，至少部分通过激活内源性大麻素系统起作用。因此，我们的数据证明了内源性大麻素系统在生殖系统对炎症信号的反应中的关键作用。
Abstract: It is known that Δ9‐tetrahydrocannabinol (THC), the major active ingredient of marijuana, can suppress reproductive function. Also, we reported previously that the endocannabinoid, anandamide (AEA), inhibited gonadotropin‐releasing hormone (LHRH) release from medial basal hypothalamus (MBH) of male rats incubated in vitro as well as reduced plasma LH levels after i.c.v. AEA injections into the cerebral lateral ventricle. On the other hand, it is known that during endotoxemia the hypothalamic gonadotropin axis is inhibited. Therefore, the aim of the present study was to determine whether the effect of TNF‐α, a proinflammatory cytokine induced by lipopolysaccharide (LPS) that inhibits LHRH release, is mediated by the activation of the endocannabinoid system. The intraperitoneal injection of LPS (5 mg/kg) as well as the i.c.v. injection of tumor necrosis factor‐α (TNF‐α) (100 ng/rat) increased significantly the AEA synthesis measured ex vivo in MBHs removed 3 h after the treatments. To examine the possibility that TNF‐α also acted by increasing the synthesis of AEA that was released and activated the CB1‐r followed by inhibition of LHRH release, we measured the effect of TNF‐α on the AEA synthase activity in MBHs incubated in vitro. As expected, we found that TNF‐α (2.9 × 10−9 M) increased the AEA synthesis. Second, we showed that TNF‐α reduced significantly the forskolin‐stimulated LHRH release and that the CB1‐r antagonist AM251 (10−5 M) blocked that inhibition, supporting the hypothesis that TNF‐α inhibits LHRH release, acting at least in part by activating the endocannabinoid system. Therefore, our data demonstrate a key role for the endocannabinoid system in the response of the reproductive system to inflammatory signals.
登录
查看更多内容
乙醇与去势大鼠中黄体生成素、卵泡刺激素和催乳素的脉冲释放。
DOI：
10.1016/0741-8329(85)90139-9
发表时间：
1985
期刊：
Alcohol (Fayetteville, N.Y.)
影响因子：
--
作者：
Dees,WL;Rettori,V;Kozlowski,GP;McCann,SM
通讯作者：
McCann,SM
δ 9-四氢大麻酚对雄性大鼠对雌性同种交配行为和神经内分泌反应的影响。
DOI：
10.1016/0091-3057(94)90213-5
发表时间：
1994
期刊：
Pharmacology, biochemistry, and behavior
影响因子：
--
作者：
Murphy,LL;Gher,J;Steger,RW;Bartke,A
通讯作者：
Bartke,A
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
发表时间：
1990
影响因子：
11.1
作者：
Rettori,V;Aguila,MC;Gimeno,MF;Franchi,AM;McCann,SM
通讯作者：
McCann,SM
由内皮 anandamide 受体介导的肠系膜血管舒张。
DOI：
10.1161/01.hyp.33.1.429
发表时间：
1999
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Wagner,JA;Varga,K;Járai,Z;Kunos,G
通讯作者：
Kunos,G
影响因子：
56.9
作者：
DEVANE, WA;HANUS, L;MECHOULAM, R
通讯作者：
MECHOULAM, R