FEMALE RATS RELEASE MORE CORTICOSTERONE THAN MALES IN RESPONSE TO ALCOHOL - INFLUENCE OF CIRCULATING SEX STEROIDS AND POSSIBLE CONSEQUENCES FOR BLOOD-ALCOHOL LEVELS
FEMALE RATS RELEASE MORE CORTICOSTERONE THAN MALES IN RESPONSE TO ALCOHOL - INFLUENCE OF CIRCULATING SEX STEROIDS AND POSSIBLE CONSEQUENCES FOR BLOOD-ALCOHOL LEVELS
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DOI：
10.1111/j.1530-0277.1993.tb00853.x
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发表时间：
1993-08-01
影响因子：
3.2
通讯作者：
RIVIER, C
中科院分区：
文献类型：
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作者：
RIVIER, C
雌性大鼠的下丘脑-垂体-肾上腺轴（HPA轴）对多种刺激的反应性比雄性大鼠更强。据报道，发情前期的女性释放更多的促肾上腺皮质激素和皮质酮，以应对约束压力比女性在发情周期的其他阶段。最后，血液酒精水平（巴尔斯）达到响应标准剂量的酒精也表明存在性别特异性，女性表现出较高的巴尔斯比男性。因此，本研究的目的是2倍：首先，我们调查了性别对酒精增加大鼠血浆ACTH和皮质酮分泌能力的影响。其次，我们检验了皮质酮改变酒精代谢的假设，并询问这是否可能代表巴尔斯性别差异的潜在机制。我们观察到，与完整的男性相比，在发情周期的随机阶段，完整的女性分泌显着（p < 0.01）更多的ACTH和皮质酮响应酒精（0.2-1.8 g/kg）。在雌性动物中，腹腔注射酒精后，发情前期和发情期的血浆ACTH和皮质类固醇水平高于发情间期。去除循环中的性类固醇取消了ACTH分泌方面的性别差异，但卵巢切除的女性仍然释放更多的皮质酮比去势的男性在0.6和1.8克酒精/公斤。这种差异不能用垂体对促肾上腺皮质激素释放因子反应性的性别相关成分来解释。这些结果表明，存在一个性别特异性激活的HPA轴在响应酒精，并表明，性类固醇激素施加激活的影响，促肾上腺皮质激素和皮质酮释放响应乙醇。可能的影响，皮质类固醇激素对酒精的药代动力学进行了研究，在完整的男性，完整的女性，和肾上腺切除（ADX）雄性动物，含15 mg（低剂量）或150 mg（高剂量）皮质酮颗粒。腹膜内注射标准剂量的乙醇（1.5 g/kg）后，低皮质酮治疗的ADX动物的巴尔斯高于完整大鼠或高皮质酮替代的ADX动物。在所有动物组中，完整雌性大鼠的皮质酮水平最高，但巴尔斯介于完整雄性大鼠和低剂量皮质酮颗粒ADX大鼠之间。因此，虽然我们不能排除身体水分含量的影响，在ADX大鼠取代各种方案的皮质类固醇，我们的研究结果表明，皮质类固醇可以调节酒精代谢的大鼠。总之，我们已经表明，在大鼠中，酒精诱导的ACTH和皮质酮分泌的性别特异性模式，似乎至少部分依赖于循环性类固醇。我们的研究结果还表明，虽然皮质类固醇激素可能在调节酒精代谢率中发挥作用，但这种作用不能解释雌性大鼠中测得的较高巴尔斯。
The hypothalamic-pituitary-adrenal (HPA) axis of female rats is more responsive to a variety of stimuli than that of males. Proestrous females are also reported to release more ACTH and corticosterone in response to restraint stress than females at other stages of the estrous cycle. Finally, blood alcohol levels (BALs) reached in response to a standard dose of alcohol also indicate the presence of a gender specificity, with females exhibiting higher BALs than males. The aim of this study was therefore 2-fold: first, we investigated the influence of gender on the ability of alcohol to increase plasma ACTH and corticosterone secretion in the rat. Second, we tested the hypothesis that corticosterone alters alcohol metabolism and asked whether this might represent a mechanism underlying the sex difference in BALs.We observed that compared with intact males, intact females taken at random stages of the estrous cycle secreted significantly (p < 0.01) more ACTH and corticosterone in response to alcohol (0.2-1.8 g/kg). Within females, the intraperitoneal administration of alcohol was followed by higher plasma ACTH and corticosteroids levels during proestrus and estrus, compared with diestrus. Removal of circulating sex steroids abolished the gender difference in terms of ACTH secretion, but ovariectomized females still released more corticosterone than castrated males in response to 0.6 and 1.8 g alcohol/kg. This difference could not be explained by a sex-related component of pituitary responsiveness to corticotropin-releasing factor. These results demonstrate the existence of a sex-specific activation of the HPA axis in response to alcohol, and suggest that sex steroids exert an activational influence on ACTH and corticosterone release in response to ethanol.The possible influence of corticosteroids on the pharmacokinetics of alcohol was investigated in intact males, intact females, and adrenalectomized (ADX) males bearing 15 mg (low dose) or 150 mg (high dose) corticosterone pellets. Following the intraperitoneal injection of a standard dose of ethanol (1.5 g/kg), ADX animals with low corticosterone therapy had higher BALs than either intact rats, or ADX animals with high corticosterone replacement. Intact females exhibited the highest corticosterone levels of all groups of animals, but showed BALs that were intermediate between those of intact males and ADX rats with the low dose corticosterone pellets. Thus, although we cannot exclude an influence of body water content in ADX rats replaced with various regimens of corticosteroids, our results indicate that corticosteroids may modulate alcohol metabolism in the rat.In summary, we have shown that, in the rat, alcohol induces a gender-specific pattern of ACTH and corticosterone secretion that appears to be at least in part dependent on circulating sex steroids. Our results also suggest that although corticosteroids may play a role in regulating the rate of alcohol metabolism, this effect cannot account for the higher BALs measured in female rats.