11-deoxycorticosterone is a potent agonist of the rainbow trout (Oncorhynchus mykiss) mineralocorticoid receptor

Endocrinology. 2005 Jan;146(1):47-55. doi: 10.1210/en.2004-0128. Epub 2004 Oct 14.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone / pharmacology
  • Amino Acid Sequence
  • Animals
  • Brain / metabolism
  • COS Cells
  • Chlorocebus aethiops
  • Cortodoxone / pharmacology
  • Desoxycorticosterone / pharmacology*
  • Hydrocortisone / pharmacology
  • Mice
  • Molecular Sequence Data
  • Oncorhynchus mykiss / metabolism*
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • RNA, Messenger / metabolism
  • Receptors, Mineralocorticoid / agonists*
  • Receptors, Mineralocorticoid / genetics
  • Receptors, Mineralocorticoid / metabolism
  • Sequence Homology, Amino Acid
  • Tissue Distribution
  • Transcriptional Activation / drug effects

Substances

  • Protein Isoforms
  • RNA, Messenger
  • Receptors, Mineralocorticoid
  • Desoxycorticosterone
  • Aldosterone
  • Cortodoxone
  • Hydrocortisone