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用生长激素治疗可恢复受照射大鼠垂体前叶细胞对下丘脑释放激素的反应性。

Responsiveness of irradiated rat anterior pituitary cells to hypothalamic releasing hormones is restored by treatment with growth hormone.

作者信息

Chiarenza A, Lempereur L, Palmucci T, Cantarella G, Amico-Roxas M, Goffin V, Murabito P, Magro G, Bernardini R

机构信息

Department of Experimental and Clinical Pharmacology, University of Catania, School of Medicine, Catania, Italy.

出版信息

Neuroendocrinology. 2000 Dec;72(6):392-9. doi: 10.1159/000054608.

Abstract

Hypopituitarism is a common sequela of irradiation in cancer patients. Here we report that recombinant human growth hormone (r-hGH) prevents cell death and restores secretory capacity of irradiated rat pituitary cells in vitro. Dispersed rat pituitary cells from male Sprague-Dawley rats, irradiated with a 9-Gy sublethal dose, were incubated with r-hGH before, after, or before and after irradiation. Treatment with GH resulted in increased cell survival, which reached its maximum at the concentration of 5 nM, with an EC(50) of 3.5 nM. Protective effects of GH on pituitary cells were more pronounced in cultures treated before and after irradiation. Similarly, beneficial effects of GH were observed on the secretory capacity of surviving cells. In fact, irradiated pituitary cells treated with GH secreted substantial amounts of GH, luteinizing hormone, follicle-stimulating hormone, prolactin, thyroid-stimulating hormone and adrenocorticotropic hormone in response to specific releasing hormones. Such effects of GH were prevented in the presence of the specific GH receptor antagonists B2036 and G120K. Our results show that r-hGH exerts a specific protective effect on irradiated rat pituitary cells and suggest possible use of GH as an adjuvant agent for prevention of postirradiation hypopituitarism.

摘要

垂体功能减退是癌症患者放疗后的常见后遗症。在此我们报告,重组人生长激素(r-hGH)可预防细胞死亡,并在体外恢复受照射大鼠垂体细胞的分泌能力。将来自雄性Sprague-Dawley大鼠的分散垂体细胞用9 Gy亚致死剂量进行照射,在照射前、照射后或照射前后与r-hGH一起孵育。用生长激素处理可提高细胞存活率,在浓度为5 nM时达到最大值,半数有效浓度(EC50)为3.5 nM。生长激素对垂体细胞的保护作用在照射前后处理的培养物中更为明显。同样,在存活细胞的分泌能力方面也观察到了生长激素的有益作用。事实上,用生长激素处理的受照射垂体细胞在受到特定释放激素刺激时,会分泌大量的生长激素、黄体生成素、促卵泡激素、催乳素、促甲状腺激素和促肾上腺皮质激素。在存在特定生长激素受体拮抗剂B2036和G120K的情况下,生长激素的这种作用被阻断。我们的结果表明,r-hGH对受照射的大鼠垂体细胞具有特异性保护作用,并提示生长激素可能作为预防放疗后垂体功能减退的辅助药物。

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