Transfection of human lactotroph adenoma cells with an adenovirus vector expressing tyrosine hydroxylase decreases prolactin release

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...

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Bibliographic Details
Published in:The journal of clinical endocrinology and metabolism 1996-06, Vol.81 (6), p.2401-2404
Main Authors: FREESE, A, DURING, M. J, DAVIDSON, B. L, GENNARELLI, T. A, KAPLITT, M. G, FLAMM, E. S, SNYDER, P. J
Format: Article
Language:English
Subjects:
Adenoma - metabolism
Adenoma - pathology
Adenoma - secretion
Adenoviridae - genetics
Adult
Biological and medical sciences
Biotechnology
Dopamine - metabolism
Endocrinopathies
Female
Fundamental and applied biological sciences. Psychology
Gene Expression
Gene therapy
Genetic Vectors
Health. Pharmaceutical industry
Humans
Hypothalamus. Hypophysis. Epiphysis (diseases)
Industrial applications and implications. Economical aspects
Levodopa - metabolism
Male
Medical sciences
Non tumoral diseases. Target tissue resistance. Benign neoplasms
Pituitary Gland, Anterior - pathology
Pituitary Neoplasms - metabolism
Pituitary Neoplasms - pathology
Pituitary Neoplasms - secretion
Prolactin - antagonists & inhibitors
Prolactin - secretion
Transfection
Tyrosine 3-Monooxygenase - genetics
Tyrosine 3-Monooxygenase - metabolism
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Summary: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.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.81.6.2401