Document Detail


Adenoviral vectors can impair adrenocortical steroidogenesis: clinical implications for natural infections and gene therapy.
MedLine Citation:
PMID:  12032309     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recombinant adenoviral vectors are effective in transferring foreign genes to a variety of cells and tissue types, both in vitro and in vivo. However, during the gene transfer, they may alter the principal function and local environment of transfected cells. Increasing evidence exists for a selective adrenotropism of adenovirus during infections and gene transfer. Therefore, using bovine adrenocortical cells in primary culture, we analyzed the influence of different adenoviral deletion mutants on cell morphology and physiology. Transfection of cells with an E1/E3-deleted adenoviral vector, engineered to express a modified form of the Aequorea victoria green fluorescent protein, was highly efficient, as documented by fluorescent microscopy. Ultrastructural analysis, however, demonstrated nuclear fragmentation and mitochondrial alterations in addition to intranuclear viral particles. Basal secretion of 17-OH-progesterone, 11-deoxycortisol, and cortisol was significantly increased by E1/E3-deleted vectors; yet, the corticotropin-stimulated release of these steroids was decreased. Interestingly, neither purified viral capsids nor E3/E4-deleted adenoviral mutants altered basal and stimulated steroidogenesis of adrenocortical cells. An intact adrenal response is crucial for adaptation to stress and survival. Therefore, the implications of our findings need to be considered in patients with adenoviral infections and those undergoing clinical studies using adenoviral gene transfer. At the same time, the high level of transfection in adrenocortical cells might make appropriately modified adenoviral vectors suitable for gene therapy of adrenocortical carcinomas with poor prognosis.
Authors:
Salvatore Alesci; Walter J Ramsey; Stefan R Bornstein; George P Chrousos; Peter J Hornsby; Salvatore Benvenga; Francesco Trimarchi; Monika Ehrhart-Bornstein
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  99     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-05-28     Completed Date:  2002-07-01     Revised Date:  2013-04-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7484-9     Citation Subset:  IM    
Affiliation:
Pediatric and Reproductive Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-1583, USA. alescis@mail.nih.gov
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics*
Adrenal Cortex / cytology,  physiology*
Adrenal Cortex Hormones / secretion*
Adrenocorticotropic Hormone / secretion
Animals
Capsid
Cattle
Cell Division / physiology
Cells, Cultured
DNA / biosynthesis
Genetic Therapy / methods*
Genetic Vectors*
Green Fluorescent Proteins
Hydrocortisone / secretion*
Infection / genetics*
Luminescent Proteins / genetics
Male
Microscopy, Electron
Recombinant Proteins / analysis
Signal Transduction
Thymidine / metabolism
Chemical
Reg. No./Substance:
0/Adrenal Cortex Hormones; 0/Luminescent Proteins; 0/Recombinant Proteins; 147336-22-9/Green Fluorescent Proteins; 50-23-7/Hydrocortisone; 50-89-5/Thymidine; 9002-60-2/Adrenocorticotropic Hormone; 9007-49-2/DNA
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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