In vitro and in vivo herpetic vector-mediated gene transfer in the pituitary gland: Impact on hormone secretion

Objective: Herpes simplex virus type 1 (HSV-1)-derived vectors are known to be effective tools to deliver transgenes into normal and neoplastic anterior pituitary (AP) cells <i>in vitro</i>. Our objective was to assess the <i>in vitro</i> and <i>in vivo</i> effect...

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Autores principales: Bolognani, Federico, Albariño, César G., Romanowski, Víctor, Carri, Néstor Gabriel, Goya, Rodolfo Gustavo
Formato: Articulo
Lenguaje:Inglés
Publicado: 2001
Materias:
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/83484
Aporte de:
id I19-R120-10915-83484
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Médicas
Ciencias Exactas
pituitary gland
hormone secretion
spellingShingle Ciencias Médicas
Ciencias Exactas
pituitary gland
hormone secretion
Bolognani, Federico
Albariño, César G.
Romanowski, Víctor
Carri, Néstor Gabriel
Goya, Rodolfo Gustavo
In vitro and in vivo herpetic vector-mediated gene transfer in the pituitary gland: Impact on hormone secretion
topic_facet Ciencias Médicas
Ciencias Exactas
pituitary gland
hormone secretion
description Objective: Herpes simplex virus type 1 (HSV-1)-derived vectors are known to be effective tools to deliver transgenes into normal and neoplastic anterior pituitary (AP) cells <i>in vitro</i>. Our objective was to assess the <i>in vitro</i> and <i>in vivo</i> effects of tsK/β-gal, a temperature-sensitive HSV-1-derived vector harbouring the <i>E. coli</i> β-galactosidase gene, on AP hormone secretion as well as on transgene expression in rat AP tumours (hyperplastic prolactinomas). Design: The impact of vector infection on prolactin (PRL) and GH release was determined <i>in vitro</i> in normal and hyperplastic (lactotrophic) dispersed AP cells exposed for 24 h to tsK/β-gal as well as <i>in vivo</i> in ectopic AP grafts. In some oestrogen-induced prolactinoma-carrying rats, vector suspension was stereotaxically injected into the glands to assess transgene expression <i>in vivo</i>. Methods: GH and PRL release was measured by specific RIAs. <i>In vivo</i> transgene expression was assessed by immunohistochemistry for β-galactosidase and enzymohistochemistry (5-bromo-4-chloro-3-indolyl-β-D-galactopyranoside). Ectopic pituitary grafts and stereotaxic surgery were performed following standard procedures. Results: At a multiplicity of infection of 0.5, the vector induced a 30 and 22% fall in PRL and GH release respectively in normal AP cells, whereas the corresponding hormone release inhibition for hyperplastic AP cells was 41 and 33% for PRL and GH respectively. In ectopic pituitary grafts, the effect of vector infection on hormone secretion was assessed by measuring serum PRL levels in the host rats every 5 days for 4 weeks post-grafting. In the pituitary-grafted rats that received the viral vector, serum PRL failed to increase to the levels achieved in control-grafted animals. Finally, pituitary tumours stereotaxically injected with tsK/β-gal showed widespread expression of the β-galactosidase transgene around the injection areas. Conclusions: The results reported here have implications for basic studies using gene transfer to pituitary gland as well as potential gene therapy approaches to pituitary diseases.
format Articulo
Articulo
author Bolognani, Federico
Albariño, César G.
Romanowski, Víctor
Carri, Néstor Gabriel
Goya, Rodolfo Gustavo
author_facet Bolognani, Federico
Albariño, César G.
Romanowski, Víctor
Carri, Néstor Gabriel
Goya, Rodolfo Gustavo
author_sort Bolognani, Federico
title In vitro and in vivo herpetic vector-mediated gene transfer in the pituitary gland: Impact on hormone secretion
title_short In vitro and in vivo herpetic vector-mediated gene transfer in the pituitary gland: Impact on hormone secretion
title_full In vitro and in vivo herpetic vector-mediated gene transfer in the pituitary gland: Impact on hormone secretion
title_fullStr In vitro and in vivo herpetic vector-mediated gene transfer in the pituitary gland: Impact on hormone secretion
title_full_unstemmed In vitro and in vivo herpetic vector-mediated gene transfer in the pituitary gland: Impact on hormone secretion
title_sort in vitro and in vivo herpetic vector-mediated gene transfer in the pituitary gland: impact on hormone secretion
publishDate 2001
url http://sedici.unlp.edu.ar/handle/10915/83484
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