Transfection of human lactotroph adenoma cells with an adenovirus vector expressing tyrosine hydroxylase decreases prolactin release.
Transfection of human lactotroph adenoma cells with an adenovirus vector expressing tyrosine hydroxylase decreases prolactin release.
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DOI：
10.1210/jcem.81.6.8964885
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发表时间：
1996-06
期刊：
影响因子：
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通讯作者：
Andrew Freese;M. During;B. Davidson;T. Gennarelli;M. Kaplitt;E. Flamm;P. Snyder
中科院分区：
文献类型：
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作者：
Andrew Freese;M. During;B. Davidson;T. Gennarelli;M. Kaplitt;E. Flamm;P. Snyder
垂体腺瘤是常见的颅内肿瘤，手术和放射通常无法治愈。在尝试开发基因疗法作为治疗垂体腺瘤的更好方法时，我们选择泌乳素腺瘤作为模型。使用该模型的基本原理是基于这样的观察：多巴胺激动剂减少催乳素腺瘤的催乳素分泌，并且还减小其大小。我们用含有编码人酪氨酸羟化酶（多巴胺生物合成中的限速酶）的cDNA的腺病毒载体转染人泌乳素腺瘤细胞的原代培养物。转染诱导酪氨酸羟化酶的表达并增加多巴胺的产生，导致预期的催乳素分泌减少的生物学效应。这些结果证明了泌乳素腺瘤和其他垂体腺瘤的基因治疗的潜力，这些垂体腺瘤比泌乳素腺瘤更不适合药物治疗。
Pituitary adenomas are common intracranial neoplasms, for which surgery and radiation are usually not curative. In attempting to develop gene therapy as a better approach to treating pituitary adenomas, we chose lactotroph adenomas as a model. The rationale for the use of this model is based on the observation that dopamine agonists decrease prolactin secretion by lactotroph adenomas, and also decrease their size. We transfected primary cultures of human lactotroph adenoma cells with an adenovirus vector containing a cDNA which encodes a human tyrosine hydroxylase, the rate-limiting enzyme in the biosynthesis of dopamine. Transfection induced expression of tyrosine hydroxylase and increased production of dopamine, resulting in the predicted biologic effect of decreased prolactin secretion. These results demonstrate the potential for gene therapy of lactotroph adenomas and perhaps other pituitary adenomas, which are less amenable to pharmacologic treatment than lactotroph adenomas.