Rettori V, Gimeno M F, Karara A, Gonzalez M C, McCann S M
Department of Physiology, University of Texas Southwestern Medical Center, Dallas 75235-9040.
Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2763-7. doi: 10.1073/pnas.88.7.2763.
Interleukin 1 alpha (IL-1 alpha), a powerful endogenous pyrogen released from monocytes and macrophages by bacterial endotoxin, stimulates corticotropin, prolactin, and somatotropin release and inhibits thyrotropin release by hypothalamic action. We injected recombinant human IL-1 alpha into the third cerebral ventricle, to study its effect on the pulsatile release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in conscious, freely moving, ovariectomized rats. Intraventricular injection of 0.25 pmol of IL-1 alpha caused an almost immediate reduction of plasma LH concentration; this decrease was statistically significant 20 min after injection and occurred through a highly significant reduction in the number of LH pulses, with no effect on pulse amplitude. In contrast, there was no change in pulse frequency but a small significant elevation in amplitude of FSH pulses. Intraventricular injection of the diluent had no effect on gonadotropin release. The results provide further evidence for separate hypothalamic control mechanisms for FSH and LH release. To determine the mechanism of the suppression of LH release, mediobasal hypothalamic fragments were incubated in vitro with IL-1 alpha (10 pM) and the release of LH-releasing hormone (LHRH) and prostaglandin E2 into the medium was measured by RIA in the presence or absence of norepinephrine (50 microM). IL-1 alpha reduced basal LHRH release and blocked LHRH release induced by norepinephrine. It had no effect on the basal release of prostaglandin E2; however, it completely inhibited the release of PGE2 evoked by norepinephrine. To evaluate the possibility that IL-1 alpha might also interfere with the epoxygenase pathway of arachidonic acid metabolism, epoxyeicosatrienoic acids were also measured. IL-1 alpha had no effect on the content of epoxyeicosatrienoic acids in the hypothalamic fragments as measured by gas chromatography and mass spectrometry. In conclusion, IL-1 alpha suppresses LH but not FSH release by an almost complete cessation of pulsatile release of LH in the castrated rat. The mechanism of this effect appears to be by inhibition of prostaglandin E2-mediated release of LHRH.
白细胞介素1α（IL-1α）是一种由细菌内毒素从单核细胞和巨噬细胞释放的强大内源性致热原，通过下丘脑作用刺激促肾上腺皮质激素、催乳素和生长激素释放，并抑制促甲状腺激素释放。我们将重组人IL-1α注入第三脑室，以研究其对清醒、自由活动、去卵巢大鼠促卵泡激素（FSH）和促黄体生成素（LH）脉冲式释放的影响。脑室内注射0.25 pmol的IL-1α几乎立即导致血浆LH浓度降低；注射后20分钟，这种降低具有统计学意义，且是通过LH脉冲数量的显著减少而发生的，对脉冲幅度没有影响。相比之下，脉冲频率没有变化，但FSH脉冲幅度有小幅显著升高。脑室内注射稀释剂对促性腺激素释放没有影响。这些结果为FSH和LH释放的下丘脑独立控制机制提供了进一步证据。为了确定LH释放受抑制的机制，将下丘脑中间基底部片段与IL-1α（10 pM）在体外孵育，并在有无去甲肾上腺素（50 microM）的情况下，通过放射免疫分析法测定培养基中促黄体生成素释放激素（LHRH）和前列腺素E2的释放。IL-1α降低了基础LHRH释放，并阻断了去甲肾上腺素诱导的LHRH释放。它对前列腺素E2的基础释放没有影响；然而，它完全抑制了去甲肾上腺素诱发的PGE2释放。为了评估IL-1α是否也可能干扰花生四烯酸代谢的环氧合酶途径，还测定了环氧二十碳三烯酸。通过气相色谱和质谱法测定，IL-1α对下丘脑片段中环氧二十碳三烯酸的含量没有影响。总之，在去势大鼠中，IL-1α通过几乎完全停止LH的脉冲式释放来抑制LH而非FSH的释放。这种作用机制似乎是通过抑制前列腺素E2介导的LHRH释放。
