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11-Deoxycorticosterone Is a Potent Agonist of the Rainbow Trout (Oncorhynchus mykiss) Mineralocorticoid Receptor

Station Commune de Recherche en Ichtyophysiologie, Biodiversité et Environnement (A.S., L.D., P.P.), Institut National de la Recherche Agronomique, Institut Fedératif de Recherche 98, 35042 Rennes-Cedex, France; King’s College London (A.S., N.B.), Division of Life Sciences, London SE1 9NN, United Kingdom; Institut National de la Santé et de la Recherche Médicale U478 (J.F., M.E.R.-O.), Institut Fédératif de Recherche 02, Faculté de Médecine Xavier Bichat, 75870 Paris Cedex 18, France; Equipe d’Endocrinologie Moléculaire de la Reproduction (G.F.), Unité Mixte de Recherche Centre National de la Recherche Scientifique 6026, Universite de Rennes I, 35042 Rennes-Cedex, France

Address all correspondence and requests for reprints to: P. Prunet, Institut National de la Recherche Agonomique SCRIBE, Campus de Beaulieu, 35042 Rennes-Cedex, France.

The teleost fish are thought to lack the mineralocorticoid hormone aldosterone but possess mineralocorticoid receptor (MR) homologs. Here we describe the characterization of two rainbow trout (Oncorhynchus mykiss) MRs, called rtMRa and rtMRb. The open reading frame of rtMRa cDNA encoded a protein of 1041 amino acids. The rtMRb predicted protein sequence is similar, differing in only 10 amino acids in the nonconserved A/B domain and lacking a three-amino acid insertion between the two zinc fingers of the C domain. Expression of rtMR mRNA (sum of both forms), measured in juvenile trout by real-time RT-PCR, shows that the transcripts are ubiquitous. Expression was significantly higher in brain than the other tissues studied (eye, trunk kidney, head kidney, gut, gills, liver, spleen, ovary, heart, white muscle, skin). Hormonal stimulation of receptor transactivation activity was studied in COS-7 cells transiently cotransfected with receptor cDNA and a mouse mammary tumor virus-luciferase reporter. The mineralocorticoids 11-deoxycorticosterone and aldosterone were more potent enhancers of rtMRa transcriptional activity (EC₅₀ = 1.6 ± 0.5 x 10^–10 and 1.1 ± 0.4 x 10^–10 M, respectively) than the glucocorticoids cortisol and 11-deoxycortisol (EC₅₀ = 1.1 ± 0.3 x 10^–9 and 3.7 ± 1.9 x 10^–9 M, respectively). A similar response was observed in transactivation assays with rtMRb. These results are discussed in the view of reported circulating levels of corticosteroids in trout.

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