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 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.
Freese
A
A
Division of Endocrinology, University of Pennsylvania Medical Center, Philadelphia, USA.
During
M J
MJ
Davidson
B L
BL
Gennarelli
T A
TA
Kaplitt
M G
MG
Flamm
E S
ES
Snyder
P J
PJ
D000236:Adenoma / Q000378:metabolism* / Q000473:pathology; D000256:Adenoviridae / Q000235:genetics; D000328:Adult; D004298:Dopamine / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D007980:Levodopa / Q000378:metabolism; D008297:Male; D010903:Pituitary Gland, Anterior / Q000473:pathology; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology; D011388:Prolactin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014162:Transfection; D014446:Tyrosine 3-Monooxygenase / Q000235:genetics* / Q000378:metabolism
D007980:Levodopa; D011388:Prolactin; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine