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

TLDR

Teleost fish lack the mineralocorticoid hormone aldosterone yet possess functional mineralocorticoid receptors. The study aimed to characterize two rainbow trout mineralocorticoid receptors, rtMRa and rtMRb. The authors cloned rtMRa and rtMRb, identified 1041‑amino‑acid proteins with minor sequence differences, and evaluated their transcriptional activation in COS‑7 cells using a luciferase reporter. Both receptors are ubiquitously expressed, especially in brain, and are strongly activated by 11‑deoxycorticosterone and aldosterone at sub‑nanomolar EC50s, whereas glucocorticoids are less potent, supporting a functional mineralocorticoid role in trout.

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.