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Transcriptional targeting to anterior pituitary lactotrophic cells using recombinant adenovirus vectors in vitro and in vivo in normal and estrogen/sulpiride-induced hyperplastic anterior pituitaries

, : Transcriptional targeting to anterior pituitary lactotrophic cells using recombinant adenovirus vectors in vitro and in vivo in normal and estrogen/sulpiride-induced hyperplastic anterior pituitaries. Endocrinology 141(9): 3493-3505

The use of pituitary cell type-specific promoters is a powerful molecular tool to achieve pituitary cell type-specific transcriptional targeting of transgenes encoded by viral vectors. It has recently been proposed that transcriptional targeting of therapeutic genes could be harnessed as a gene therapy strategy for the treatment of pituitary disease. We describe the successful use of the human PRL promoter (hPrl) encoded within recombinant adenovirus vectors to target transgene expression of Herpes Simplex Virus Type 1-Thymidine Kinase (HSV1-TK) or beta-galactosidase to lactotrophic cells in vitro and in vivo. Functionally, the restriction of expression of HSV1-TK to lactotrophic tumor cells, using the hPrl promoter, resulted in the cell type-specific induction of apoptosis in the lactotrophic GH3 tumor cell line, in the presence of ganciclovir (GCV). In the corticotrophic AtT20 cell line, we detected neither HSV1-TK expression, nor apoptosis in the presence of GCV. The hPrl promoter encoded within a recombinant adenoviral vector also restricted transgene expression to lactotrophic cells in primary anterior pituitary (AP) cultures, and importantly, within the anterior pituitary gland in vivo. When the HSV1-TK driven by hPrl promoter was used in an in vivo model of estrogen/sulpiride lactotroph induced hyperplasia within the AP in situ, the treatment was not effective in either reducing the weight of the gland, the number of lactotrophic cells within the transduced area in vivo, or the circulating PRL levels. This is in contrast to the human cytomegalovirus promoter (hCMV) driving expression of HSV1-TK in the same experimental paradigm, which was effective in reducing pituitary weight and circulating PRL levels. Our results have important implications in the design of gene therapy strategies for pituitary tumors. We demonstrate that both the choice of the in vivo animal model, i.e. adenoma in the AP gland in situ, and the particular gene therapy strategy chosen, i.e. use of strong ubiquitous promoters vs. weaker but cell type-specific promoters, determine the experimental therapeutic outcome.


PMID: 10965923

DOI: 10.1210/endo.141.9.7639

Other references

Wojciechowski, J.P.zacki, W., 1978: Evaluating even heating throughout a canned meat product. II. Effect of dimensions in cylindrical packs. Fleischwirtschaft 58(12): 1990

Nasilowski, W.; Rudowski, W., 1975: Infection as a basic problem in the treatment of burns. Polski Tygodnik Lekarski 30(20): 833-835

Phillips, J.E.; Wong, L.B.; Yeates, D.B., 1999: Bidirectional transepithelial water transport: measurement and governing mechanisms. In the search for the mechanisms whereby water is transported across biological membranes, we hypothesized that in the airways, the hydration of the periciliary fluid layer is regulated by luminal-to-basolateral water transport coupled to active t...

Hudson, R.P.; Chong, P.Andrew.; Protasevich, I.I.; Vernon, R.; Noy, E.; Bihler, H.; An, J.Li.; Kalid, O.; Sela-Culang, I.; Mense, M.; Senderowitz, H.; Brouillette, C.G.; Forman-Kay, J.D., 2012: Conformational changes relevant to channel activity and folding within the first nucleotide binding domain of the cystic fibrosis transmembrane conductance regulator. Deletion of Phe-508 (F508del) in the first nucleotide binding domain (NBD1) of the cystic fibrosis transmembrane conductance regulator (CFTR) leads to defects in folding and channel gating. NMR data on human F508del NBD1 indicate that an H620Q mut...

Wai,J.S.; Sridith,K.; Thaithong,O., 2008: Hoya imperialis Lindl , a new record for Thailand. <i>Hoya imperialis</i> Lindl. is newly recorded for Thailand from Belong district in Yala province. The species is described and illustrated.

Bunn, C.E.E.; Burch, J.E., 1955: Hydro-cortisone in the treatment of traumatic arthritis in Thoroughbreds. Hydrocortisone treatment by instillation into the carpal and fetlock joints of 137 acute and 318 chronic cases of traumatic arthritis in Thoroughbred horses decreased pain, swelling, and heat and increased mobility within a few hours. Treated hors...

Blaas, H-G.K.; Eik-Nes, S.H., 2009: Sonoembryology and early prenatal diagnosis of neural anomalies. In the following review, the early development of the central nervous system (CNS), as described by embryologists and anatomists in modern embryological textbooks, is compared with sonoanatomic descriptions from two-dimensional (2D) and three-dime...

Mielke, H.W.; Gonzales, C.R.; Powell, E.T.; Mielke, P.W., 2013: Environmental and health disparities in residential communities of New Orleans: the need for soil lead intervention to advance primary prevention. Urban environments are the major sites for human habitation and this study evaluates soil lead (Pb) and blood Pb at the community scale of a U.S. city. There is no safe level of Pb exposure for humans and novel primary Pb prevention strategies are...

Eisner, T.; McCormick, K.D.; Sakaino, M.; Eisner, M.; Smedley, S.R.; Aneshansley, D.J.; Deyrup, M.; Myers, R.L.; Meinwald, J., 1990: Chemical defense of a rare mint plant. Chemoecology 1(1): 30-37

Cropper, Rs, 1984: True bugs (Hemiptera). Proceedings of the Bristol Naturalists' Society1984]; 43: 57