MODE OF ACTION OF INTERLEUKIN-1 IN SUPPRESSION OF PITUITARY LH-RELEASE IN CASTRATED MALE-RATS
MODE OF ACTION OF INTERLEUKIN-1 IN SUPPRESSION OF PITUITARY LH-RELEASE IN CASTRATED MALE-RATS
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DOI：
10.1016/0006-8993(93)91637-8
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发表时间：
1993-05-28
期刊：
影响因子：
2.9
通讯作者：
KALRA, PS
中科院分区：
文献类型：
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作者：
BONAVERA, JJ;KALRA, SP;KALRA, PS
这些研究旨在阐明细胞因子白介素1(IL-1)抑制去大鼠垂体促黄体激素释放的机制。由于去势大鼠黄体生成素的分泌是搏动性的，因此，我们观察了IL-1对黄体生成素搏动性成分的影响。脑室内(i.c.v.)IL-1α或IL-1β可抑制黄体生成素的释放，但在起效时间(IL-1β=30min；IL-1α=105min)以及抑制黄体生成素的幅度和持续时间方面，IL-1β比IL-1α更为有效。此外，IL-1β处理的大鼠的黄体生成素分泌显著抑制是由于黄体生成素发作的频率和幅度都显著减少。接下来，我们评估了IL-1β诱导的促黄体生成素释放抑制是否由下丘脑促肾上腺皮质激素释放激素(CRH)和内源性阿片肽(EOP)这两个抑制下丘脑肽能系统中的任何一个所介导。静脉注射被动免疫中和治疗CRH。注射IL-1β前15分钟注射CRH抗体1次，或注射IL-1β前75分钟和15分钟注射CRH抗体2次，均不能阻断IL-1β对促黄体生成素释放的抑制作用。同样，静脉注射对CRH的药理阻断作用。IL-1β无效前15分钟注射CRH受体拮抗剂α-螺旋CRH9-41。然而，静脉注射。输注阿片受体拮抗剂纳洛酮本身对促黄体生成素的分泌没有影响，可抵消IL-1β的抑制作用。为了进一步确定所涉及的阿片受体亚型，我们使用了特定的阿片受体亚型拮抗剂。我们观察到，注射IL-1β后，无论是用纳曲吲哚阻断Delta受体，还是用去甲肾上腺素二盐酸盐阻断kappa受体，都不能改变黄体生成素抑制的过程。然而，预先用盐酸呋喃甲氨蝶呤阻断MU1阿片受体，可完全逆转IL-1β对黄体生成素释放的抑制作用。这些结果表明，IL-1β对去势大鼠黄体生成素的放电频率和幅度均有抑制作用。进一步的药理学证据表明，IL-1β诱导的促黄体生成素分泌抑制可能与刺激下丘脑内源性阿片类药物有关，这种作用可能是通过下丘脑MU1阿片受体亚型起作用的，而刺激下丘脑CRH释放可能不是IL-1β抑制促黄体生成素释放所必需的。
These studies were undertaken to elucidate the mechanisms whereby the cytokine, Interleukin (IL-1) suppresses pituitary LH release in orchidectomized rats. Since LH secretion is pulsatile in castrated rats, the effects of IL-1 on the components of the LH pulsatility were assessed. Intracerebroventricular (i.c.v.) administration of IL-1alpha or IL-1beta suppressed LH release, but IL-1beta was relatively more effective than IL-1alpha in terms of the onset (IL-1beta = 30 min; IL-1alpha = 105 min) as well as the magnitude and duration of LH suppression. Further, the marked suppression of LH secretion in IL-1beta-treated rats was found to be due to significant reductions both in the frequency and amplitude of LH episodes. We next evaluated whether the IL-1beta-induced suppression of LH release was mediated by either of the two inhibitory hypothalamic peptidergic systems, corticotrophin releasing hormone (CRH) and endogenous opioid peptides (EOP). Passive immunoneutralization of CRH by i.c.v. administration of a specific CRH-antibody, either once at 15 min or twice at 75 and 15 min before IL-1beta injection, failed to block the suppressive effects of IL-1beta on LH release. Similarly, pharmacological blockade of CRH by i.c.v. injection of the CRH receptor antagonist, alpha-helical CRH9-41 15 min before IL-1beta was ineffective. However, i.v. infusion of the opiate receptor antagonist, naloxone, which on its own had no effect on LH secretion, counteracted the inhibitory effects of IL-1beta. To further identify the opiate receptor subtype involved, we utilized specific opiate receptor subtype antagonists. We observed that neither blockade of delta receptors with naltrindole, nor blockade of kappa receptors with nor-binaltorphimine dihydrochloride, altered the course of LH suppression seen after IL-1beta injection. However, prior blockade of mu1 opiate receptors with beta-funaltrexamine hydrochloride, completely reversed the inhibitory effects of IL-1beta on LH release. These results show that IL-1beta suppresses both the frequency and amplitude of LH discharge in two-week castrated rats. Further pharmacologic evidence shows that IL-1beta-induced suppression of LH secretion may involve stimulation of hypothalamic endogenous opioids which presumably act via the hypothalamic mu1 opiate receptor subtype, and that stimulation of hypothalamic CRH release may not be essential in manifestation of the inhibitory effects of IL-1beta on LH release.