Maintenance of gonadotropin secretion by glucocorticoids under stress conditions through the inhibition of prostaglandin synthesis in the brain
Maintenance of gonadotropin secretion by glucocorticoids under stress conditions through the inhibition of prostaglandin synthesis in the brain
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DOI：
10.1210/en.2005-1056
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发表时间：
2006-03-01
期刊：
影响因子：
4.8
通讯作者：
Nishihara, M
中科院分区：
文献类型：
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作者：
Matsuwaki, T;Kayasuga, Y;Nishihara, M
我们以前曾报道，糖皮质激素可以抵消肿瘤坏死因子-α对黄体生成素搏动性和波动性分泌的抑制作用。提示糖皮质激素在感染应激状态下对生殖功能具有保护作用。在本研究中，我们研究了糖皮质激素是否在不同的急性应激条件下维持搏动性的促黄体生成素分泌，以及前列腺素(PGs)可能参与糖皮质激素的作用。对去卵巢大鼠施加3种不同类型的应激源，即感染性应激源(脂多糖，0.5mU/kg)、低血糖应激源(2-脱氧-D-葡萄糖，100 mg/kg)和束缚应激源(1h)。在去卵巢大鼠，束缚可部分抑制黄体生成素脉冲，但不能被脂多糖或2-脱氧-D-葡萄糖抑制。另一方面，肾上腺切除(ADX)显著增强了所有应激源对促黄体生成素脉冲的抑制作用。皮质酮(25 mg/kg)和消炎痛(10 mg/kg)对ADX大鼠的治疗可显著减弱这些应激源对黄体生成素脉搏的抑制作用。此外，应激条件下脑内PG合成酶环氧合酶-2的免疫反应性被ADX大大增强，这一免疫反应可被皮质酮处理所抵消。同样，束缚应激下的体温升高可被ADX增强，而被皮质酮抑制。这些结果表明，应激抑制黄体生成素的搏动性是由大脑中的前列腺素介导的，内源性糖皮质激素的释放增加是通过抑制PG的合成来抵消这种抑制，从而维持生殖功能，而不考虑应激源的性质。
We have previously reported that glucocorticoids counteract the suppressive effects of tumor necrosis factor-alpha on both pulsatile and surge secretion of LH. This suggests that glucocorticoids have a protective effect on reproductive function under infectious stress. In the present study, we examined whether glucocorticoids maintain pulsatile LH secretion under various conditions of acute stress and the possible involvement of prostaglandins (PGs) in glucocorticoid actions. Three different types of stressors, namely infectious ( lipopolysaccharide, 0.5 mu g/ kg), hypoglycemic (2-deoxy-D-glucose, 100 mg/ kg), and restraint stress (1 h) were applied to ovariectomized rats. In ovariectomized rats, LH pulses were partially suppressed by restraint, but not by lipopolysaccharide or 2-deoxy-D-glucose. On the other hand, adrenalectomy (ADX) significantly enhanced the suppressive effects of all the stressors applied on LH pulses. Treatment with both corticosterone (25 mg/ kg) and indomethacin (10 mg/ kg) in ADX rats significantly attenuated the suppressive effects of these stressors on LH pulses. In addition, the immunoreactivity of cyclooxygenase-2, a PG-synthesizing enzyme, in the brain under stress conditions was much enhanced by ADX, and this was counteracted by corticosterone treatment. Similarly, an increase in body temperature under restraint stress was enhanced by ADX and suppressed by corticosterone. These results suggest that suppression of LH pulsatility by stress is mediated by PGs in the brain, and that increased release of endogenous glucocorticoids in response to stress counteracts this suppression by inhibiting PG synthesis, and thereby maintains reproductive function regardless of the nature of the stressor.