AN INHIBITORY EFFECT OF INTERLEUKIN-1A ON BASAL GONADOTROPIN-RELEASE IN THE OVARIECTOMIZED RHESUS-MONKEY - REVERSAL BY A CORTICOTROPIN-RELEASING FACTOR ANTAGONIST
AN INHIBITORY EFFECT OF INTERLEUKIN-1A ON BASAL GONADOTROPIN-RELEASE IN THE OVARIECTOMIZED RHESUS-MONKEY - REVERSAL BY A CORTICOTROPIN-RELEASING FACTOR ANTAGONIST
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DOI：
10.1210/endo-128-4-2077
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发表时间：
1991-04-01
期刊：
影响因子：
4.8
通讯作者：
FERIN, M
中科院分区：
文献类型：
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作者：
FENG, YJ;SHALTS, E;FERIN, M
白介素1(IL-1)是免疫系统的重要组成部分，近年来研究表明，IL-1可影响啮齿动物体内多种激素的释放。本文研究了IL-1a对灵长类基础促性腺激素分泌和皮质醇释放的调节作用。8只成年恒河猴去卵巢后，侧脑室注射生理盐水(n=5)、不同剂量的IL-1a(17mU-g：n=5；8.5-mU-g：3；4.2-mU-g：n=5；2.1-mU-g：n=4)或IL-1a加CRF拮抗剂(n=5)。在输注前3h基线对照和输注后5h期间，每隔15分钟测定促黄体生成素和卵泡刺激素浓度，每隔45分钟测定皮质醇浓度。在只接受生理盐水的猴子中，黄体生成素浓度保持不变，但在注射IL-1a 30分钟后，它们显著下降。在注射IL-1a后5小时，黄体生成素曲线下平均每小时面积(+/-SE)分别为27.7%+/-7.3(17-mU-g IL-1a)、31.9%+/-8.4(8.5-mU-g)、33.3%+/-5.5(4.2-mU-g)和39%+/-4.0(2.1-mU-g)(P<；0.05与上午对照组相比)。IL-1a、17-mU-g治疗后FSH水平也显著降低，至5h时为基线对照的67.4%+/-5.0。在接受生理盐水的动物中，皮质醇浓度在实验结束后下降，但随着所有IL-1a剂量的增加而增加：总平均浓度(+/-SE)为21.8+/-1.1(生理盐水)，49.5+/-2.2(IL-1a，17-mU-g)，35.1+/-1.9(8.5-mU-g)，45.7+/-1.5(4.2-mU-g)，和39.5+/-1.5(2.1-m-g)Mu-g/dl(P<；0.05 IL-1a与生理盐水比较)。同时输注CRF拮抗剂[D-PHE12，NLE 21.38，C(A)Me LEU37]CRF(12-41)，(120-360-mU-g)可阻断IL-1a对黄体生成素的抑制作用。5小时后，单独使用IL-1a的黄体生成素曲线下面积为33.5%+/-1.7，使用IL-1a+CRF拮抗剂的黄体生成素曲线下面积为99.2%+/-4.2(生理盐水与生理盐水相比)。CRF拮抗剂也阻断了IL-1a增加皮质醇分泌的能力：平均皮质醇浓度为28.6+/-1.4-mU-g/dl(NS比生理盐水)。结果清楚地表明，细胞因子IL-1a抑制卵巢切除恒河猴搏动性的促黄体生成素和卵泡刺激素分泌，并证明这种抑制作用与该细胞因子激活促肾上腺皮质激素释放激素有关。因此，这些数据为灵长类的免疫系统与肾上腺和生殖系统之间的联系提供了具体的证据。
Interleukin-1 (IL-1), an important component of the immune system, has recently been shown to influence the release of several hormones in the rodent. In this paper, the effectiveness of IL-1a in modulating basal gonadotropin secretion as well as cortisol release in the primate has been investigated. Eight adult ovariectomized rhesus monkeys were given a 30-min intracerebroventricular infusion of physiological saline (n = 5), various doses of IL-1a (17-mu-g: n = 5; 8.5-mu-g: n = 3; 4.2-mu-g: n = 5; and 2.1-mu-g: n = 4) or IL-1a plus a CRF antagonist (n = 5). LH and FSH concentrations were measured at 15-min intervals during the 3-h preinfusion baseline control and the 5-h postinfusion period, while cortisol concentrations were determined at 45-min intervals. While LH concentrations remained unchanged in the monkeys receiving saline only, they decreased significantly after the 30-min IL-1a infusion. By hour 5 after IL-1a administration, mean (+/- SE) hourly areas under the LH curves (expressed as a percentage of preinfusion baseline) were 27.7% +/- 7.3 (17-mu-g IL-1a), 31.9% +/- 8.4 (8.5-mu-g), 33.3% +/- 5.5 (4.2-mu-g), and 39% +/- 4.0 (2.1-mu-g) (P < 0.05 vs. morning control). FSH concentrations were also significantly decreased after IL-1a, 17-mu-g: by hour 5, they were 67.4% +/- 5.0 of baseline control. While cortisol concentrations decreased thoughout the experiment in the animals receiving saline, they increased with all IL-1a doses: overall mean (+/-SE) postinfusion concentrations were 21.8 +/- 1.1 (saline), 49.5 +/- 2.2 (IL-1a, 17-mu-g), 35.1 +/- 1.9 (8.5-mu-g), 45.7 +/- 1.5 (4.2-mu-g), and 39.5 +/- 1.5 (2.1-mu-g) mu-g/dl (P < 0.05 IL-1a vs, saline). Concomitant infusion of the CRF antagonist, [D-PHE12, NLE 21.38,C(a) Me LEU37] CRF (12-41), (120-360-mu-g), prevented the IL-1a induced LH inhibition. By hour 5, areas under LH curves were 33.5% +/- 1.7 for IL-1a alone and 99.2% +/- 4.2 (NS vs. saline) for IL-1a + CRF antagonist. The CRF antagonist also blocked the ability of IL-1a to increase cortisol secretion: mean cortisol concentrations were 28.6 +/- 1.4-mu-g/dl (NS vs. saline).The results clearly indicate that the cytokine IL-1a inhibits pulsatile LH and FSH secretion in the ovariectomixed rhesus monkey and demonstrate that this inhibition is causally related to the activation of CRF by this cytokine. Thus, the data provide specific evidence for a linkage between the immune system and the adrenal and reproductive systems in the primate.