Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 351074
Title Evolution of glucocorticoid receptors with different glucocorticoid sensitivity
Author(s) Stolte, H.H.; Verburg-van Kemenade, B.M.L.; Savelkoul, H.F.J.; Flik, G.
Source Journal of Endocrinology 190 (2006)1. - ISSN 0022-0795 - p. 17 - 28.
Department(s) Cell Biology and Immunology
Publication type Refereed Article in a scientific journal
Publication year 2006
Keyword(s) dna-binding domain - cyprinus-carpio l - teleost fish - guinea-pig - steroid sensitivity - hormone-receptors - plasma-cortisol - stress-response - common carp - mechanisms
Abstract Glucocorticoids (GCs) are commonly used to treat a variety of immune diseases. However, the efficacy of treatment is greatly influenced by an individual variation in sensitivity to GCs, which is caused by differences in the glucocorticoid receptor (GR). The variable receptor profile results from variations in the GR gene, or alternative splicing of the gene coded. We investigated the evolution of the GR gene by comparing genomic GR sequences of vertebrates. Exon length and amino acid sequence are conserved among all classes of vertebrates studied, which indicates strong evolutionary pressure on conservation of this gene. Interestingly, teleostean fishes have two different GR proteins. One of the duplicate fish GR, genes has a nine-amino-acid insert in the DNA binding region that results from alternative splicing. The duplicate GR genes and products of alternative splicing in teleostean fishes are differentially expressed in vivo and show different transactivation capacity in vitro. The presence of two GR genes appears to be a result of divergence of receptors rather than of ligands. Teleostean fishes express different, evolutionarily related, functional GR proteins within a single organism. Hereby, teleostean fishes present a model that facilitates investigation of the molecular basis of cortisol resistance and different regulatory functions of cortisol
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