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犬乳腺肿瘤中生长激素/胰岛素样生长因子-I轴与甾体激素(孕酮、17β-雌二醇)之间的相互作用

Crosstalk between GH/IGF-I axis and steroid hormones (progesterone, 17beta-estradiol) in canine mammary tumours.

作者信息

Queiroga Felisbina L, Pérez-Alenza Maria D, Silvan Gema, Peña Laura, Lopes Carlos S, Illera Juan C

机构信息

CECAV, Department of Veterinary Sciences, Universidade de Trás-os-Montes e Alto Douro, 5001-801 Vila Real, Portugal.

出版信息

J Steroid Biochem Mol Biol. 2008 May;110(1-2):76-82. doi: 10.1016/j.jsbmb.2008.02.005. Epub 2008 Feb 14.

Abstract

Growth hormone (GH), insulin-like growth factor I (IGF-I), progesterone (P4) and 17beta-estradiol (17-E2) concentrations have been studied in 84 mammary tumours (44 dysplasias and benign tumours and 40 malignant neoplasias) from 33 female dogs. Thirteen normal mammary glands from 80 healthy female dogs were also analysed as controls. GH concentrations were determined in mammary homogenates by radio-immunoassay. IGF-I, P4 and 17-E2 tissue levels were determined by enzyme-immunoassay (EIA) techniques. The potential correlations between GH/IGF-I concentrations and P4 and 17-E2 mammary tissue levels were investigated. Tissue GH (p<0.01) and IGF-I concentrations (p<0.01) were significantly higher in malignant tumours than in benign neoplasms. Likewise, malignant tumours were the mammary lesions that displayed the highest P4 and 17-E2 tissue levels. Strong correlations between GH/IGF-I (n=84; r=0.436; p<0.001), P4/GH (n=84; r=0.562; p<0.001) and 17-E2/IGF-I (n=84; r=0.638; p<0.001) were observed in tumoral tissue homogenates. Our study provides evidence that P4 might increase autocrine GH production which might directly stimulate local or systemic IGF-I secretion. Additionally, the IGF-I effect might be influenced by local levels of 17-E2. These results suggest that all these hormones and factors might act as local growth factors stimulating the development and/or maintenance of canine mammary tumours in an autocrine/paracrine manner.

摘要

对33只雌性犬的84个乳腺肿瘤(44个发育异常和良性肿瘤以及40个恶性肿瘤)进行了生长激素(GH)、胰岛素样生长因子I(IGF-I)、孕酮(P4)和17β-雌二醇(17-E2)浓度的研究。还分析了80只健康雌性犬的13个正常乳腺作为对照。通过放射免疫测定法测定乳腺匀浆中的GH浓度。通过酶免疫测定(EIA)技术测定IGF-I、P4和17-E2的组织水平。研究了GH/IGF-I浓度与P4和17-E2乳腺组织水平之间的潜在相关性。恶性肿瘤中的组织GH(p<0.01)和IGF-I浓度(p<0.01)显著高于良性肿瘤。同样,恶性肿瘤是显示出最高P4和17-E2组织水平的乳腺病变。在肿瘤组织匀浆中观察到GH/IGF-I(n = 84;r = 0.436;p<0.001)、P4/GH(n = 84;r = 0.562;p<0.001)和17-E2/IGF-I(n = 84;r = 0.638;p<0.001)之间存在强相关性。我们的研究提供了证据表明P4可能会增加自分泌GH的产生,这可能直接刺激局部或全身IGF-I的分泌。此外,IGF-I的作用可能受局部17-E2水平的影响。这些结果表明,所有这些激素和因子可能作为局部生长因子,以自分泌/旁分泌方式刺激犬乳腺肿瘤的发生和/或维持。

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