Regulation of the hypothalamic-pituitary-adrenal axis circadian rhythm by endocannabinoids is sexually diergic.
Regulation of the hypothalamic-pituitary-adrenal axis circadian rhythm by endocannabinoids is sexually diergic.
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DOI：
10.1210/en.2010-0101
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发表时间：
2010-08
期刊：
影响因子：
4.8
通讯作者：
Lightman SL
中科院分区：
文献类型：
--
作者：
Atkinson HC;Leggett JD;Wood SA;Castrique ES;Kershaw YM;Lightman SL
我们已经研究了大麻素受体1型（CB 1）拮抗剂AM 251对大鼠下丘脑-垂体-肾上腺（HPA）轴的急性给药的影响，性别和时间的一天。使用自动采血系统每5分钟从清醒的雄性和雌性大鼠中采集血样，并测定皮质酮浓度。在雄性大鼠中，AM 251具有明显的昼夜效应，早晨（昼夜谷值）HPA轴的激活程度高于晚上（昼夜峰值）。在一天中的两个时间点，AM 251给药后循环皮质酮浓度升高约4 h。在雌性大鼠中，HPA轴的激活也存在昼夜变化;然而，这些影响不如雄性大鼠深刻。皮质酮浓度仅在昼夜谷值时略有升高，且持续时间短于雄性（2小时与4小时相比）。此外，当在昼夜高峰给药时，AM 251对皮质酮浓度没有影响。随后的研究，仅在男性，其中ACTH和皮质酮都进行了测量，证实了AM 251对皮质酮的影响是由ACTH介导的。此外，使用另一种CB 1拮抗剂AM 281可以复制ACTH和皮质酮的升高。这些数据表明，CB 1阻断后HPA轴激活的程度和持续时间明显取决于性别和时间。CB 1受体阻断后HPA轴激活的程度和持续时间明显依赖于大鼠的性别和时间。
We have examined the effects of acute administration of the cannabinoid receptor type 1 (CB1) antagonist AM251 on the rat hypothalamic-pituitary-adrenal (HPA) axis with respect to both gender and time of day. Blood samples were collected from conscious male and female rats every 5 min using an automated blood sampling system, and corticosterone concentrations were determined. In male rats, there was a distinct diurnal effect of AM251 with a greater activation of the HPA axis in the morning (diurnal trough) compared with the evening (diurnal peak). At both times of the day, circulating corticosterone concentrations were elevated for approximately 4 h after AM251 administration. In female rats, there was also diurnal variation in the activation of the HPA axis; however, these effects were not as profound as those in males. Corticosterone concentrations were only slightly elevated at the diurnal trough and for a shorter time period than in males (2 compared with 4 h). Moreover, there was no effect of AM251 on corticosterone concentrations when administered at the diurnal peak. Subsequent studies, only in males, in which both ACTH and corticosterone were measured, confirmed that the effects of AM251 on corticosterone were mediated by ACTH. Moreover, the elevation of both ACTH and corticosterone could be replicated using another CB1 antagonist, AM281. These data demonstrate that the extent and duration of HPA axis activation after CB1 blockade are clearly dependent on both gender and time of day. The extent and duration of HPA axis activation following CB1 receptor blockade are clearly dependent on both sex of rat and time of day.
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影响因子：
4.8
作者：
Patel, S;Roelke, CT;Hillard, CJ
通讯作者：
Hillard, CJ
影响因子：
3.2
作者：
HORROCKS, PM;JONES, AF;LONDON, DR
通讯作者：
LONDON, DR
影响因子：
56.9
作者：
Balsalobre, A;Brown, SA;Schibler, U
通讯作者：
Schibler, U
影响因子：
2.9
作者：
Manzanares, J;Corchero, J;Fuentes, JA
通讯作者：
Fuentes, JA
DOI：
10.1073/pnas.0404366101
发表时间：
2004-08-10
影响因子：
11.1
作者：
Scorticati, C;Fernández-Solari, J;Rettori, V
通讯作者：
Rettori, V