The role of ‘mineralocorticoids’ in teleost fish: Relative importance of glucocorticoid signaling in the osmoregulation and ‘central’ actions of mineralocorticoid receptor

Takahashi, Hideya; Sakamoto, Tatsuya

doi:10.1016/j.ygcen.2012.11.016

Cited by 120 publications

(96 citation statements)

References 54 publications

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“…The mineralocorticoid system in fish may have biological actions in the brain and in behavior rather than in osmoregulation8121314, particularly in visuomotor performance, based on MR localization found in medaka ( Oryzias latipes ) in the present study. This fish is a useful model organism for studying these functions due to its tolerance to a wide range of salinities and several quantifiable behaviors.…”

supporting

confidence: 52%

“…The counterparts of tetrapod MRs and their specific endogenous ligand, 11-deoxycorticosterone (DOC), have only recently been identified4567. The effects of MR/GR agonists/antagonists and the dynamics of DOC/cortisol-MR/GR expressions indicate a minor role of mineralocorticoid signaling (DOC/cortisol-MR) in osmoregulation compared with that of glucocorticoid signaling (cortisol-GR)8. Thus, the function of the mineralocorticoid system in teleost fish has yet to be established.…”

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confidence: 99%

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Principal function of mineralocorticoid signaling suggested by constitutive knockout of the mineralocorticoid receptor in medaka fish

Sakamoto

Yoshiki

Takahashi

et al. 2016

Sci Rep

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As in osmoregulation, mineralocorticoid signaling is implicated in the control of brain-behavior actions. Nevertheless, the understanding of this role is limited, partly due to the mortality of mineralocorticoid receptor (MR)-knockout (KO) mice due to impaired Na+ reabsorption. In teleost fish, a distinct mineralocorticoid system has only been identified recently. Here, we generated a constitutive MR-KO medaka as the first adult-viable MR-KO animal, since MR expression is modest in osmoregulatory organs but high in the brain of adult medaka as for most teleosts. Hyper- and hypo-osmoregulation were normal in MR-KO medaka. When we studied the behavioral phenotypes based on the central MR localization, however, MR-KO medaka failed to track moving dots despite having an increase in acceleration of swimming. These findings reinforce previous results showing a minor role for mineralocorticoid signaling in fish osmoregulation, and provide the first convincing evidence that MR is required for normal locomotor activity in response to visual motion stimuli, but not for the recognition of these stimuli per se. We suggest that MR potentially integrates brain-behavioral and visual responses, which might be a conserved function of mineralocorticoid signaling through vertebrates. Importantly, this fish model allows for the possible identification of novel aspects of mineralocorticoid signaling.

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confidence: 52%

mentioning

confidence: 99%

Principal function of mineralocorticoid signaling suggested by constitutive knockout of the mineralocorticoid receptor in medaka fish

Sakamoto

Yoshiki

Takahashi

et al. 2016

Sci Rep

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“…Altogether, these results suggest that GR-MR interaction mediates a repertoire of cellular responses to GC in various tissues. Such regulatory pathways probably exist in the fish brain to regulate behavior or exist in osmoregulatory tissues where both the GR and the MR are involved (Kiilerich et al 2007, 2011a, b, c, McCormick et al 2008, Sakamoto et al 2011, Takahashi & Sakamoto 2013. The MR mediated repression of GR activity reported in this study certainly adds new possibilities to a search for a physiologically relevant function of the MR in fish and requires further studies.…”

Section: Figurementioning

confidence: 62%

Interaction between the trout mineralocorticoid and glucocorticoid receptors in vitro

Kiilerich¹,

Triqueneaux²,

Christensen³

et al. 2015

Journal of Molecular Endocrinology

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The salmonid corticosteroid receptors (CRs), glucocorticoid receptors 1 and 2 (GR1 and GR2) and the mineralocorticoid receptor (MR) share a high degree of homology with regard to structure, ligand-and DNA response element-binding, and cellular co-localization. Typically, these nuclear hormone receptors homodimerize to confer transcriptional activation of target genes, but a few studies using mammalian receptors suggest some degree of heterodimerization. We observed that the trout MR confers a several fold lower transcriptional activity compared to the trout GRs. This made us question the functional relevance of the MR when this receptor is located in the same cells as the GRs and activated by cortisol. A series of co-transfection experiments using different glucocorticoid response elements (GREs) containing promoter-reporter constructs were carried out to investigate any possible interaction between the piscine CRs. Co-transfection of the GRs with the MR significantly reduced the total transcriptional activity even at low MR levels, suggesting interaction between these receptors. Co-transfection of GR1 or GR2 with the MR did not affect the subcellular localization of the GRs, and the MR-mediated inhibition seemed to be independent of specific activation or inhibition of the MR. Site-directed mutagenesis of the DNA-binding domain and dimerization interface of the MR showed that the inhibition was dependent on DNA binding but not necessarily on dimerization ability. Thus, we suggest that the interaction between MR and the GRs may regulate the cortisol response in cell types where the receptors co-localize and propose a dominant-negative role for the MR in cortisolmediated transcriptional activity.

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“…The absence of Aldo in fish has led to speculation that F and DOC may be a physiological mineralocorticoid for fish (Baker 2003, Sturm et al 2005, Prunet et al 2006, Baker et al 2007, Bury & Sturm 2007, McCormick et al 2008, Arterbery et al 2011, Sakamoto et al 2011, Takahashi & Sakamoto 2013, Sakamoto et al 2016. Interestingly, Prog is a transcriptional activator of ray-finned fish, which also respond to 19-norProg and spironolactone (Sturm et al 2005, Pippal et al 2011, Sugimoto et al 2016).…”

Section: Transcriptional Activation Of Fish Mr By Prog a Possible MImentioning

confidence: 99%

30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Evolution of the mineralocorticoid receptor: sequence, structure and function

Baker

Katsu

2017

Journal of Endocrinology

119

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The mineralocorticoid receptor (MR) is descended from a corticoid receptor (CR), which has descendants in lamprey and hagfish, cyclostomes (jawless fish), a taxon that evolved at the base of the vertebrate line. A distinct MR and GR first appear in cartilaginous fishes (Chondrichthyes), such as sharks, skates, rays and chimeras. Skate MR has a strong response to corticosteroids that are mineralocorticoids and glucocorticoids in humans. The half-maximal responses (EC50s) for skate MR for the mineralocorticoids aldosterone and 11-deoxycorticosterone are 0.07 nM and 0.03 nM, respectively. EC50s for the glucocorticoids cortisol and corticosterone are 1 nM and 0.09 nM, respectively. The physiological mineralocorticoid in ray-finned fish, which do not synthesize aldosterone, is not fully understood because several 3-ketosteroids, including cortisol, 11-deoxycortisol, corticosterone, 11-deoxycorticosterone and progesterone are transcriptional activators of fish MR. Further divergence of the MR and GR in terrestrial vertebrates, which synthesize aldosterone, led to emergence of aldosterone as a selective ligand for the MR. Here, we combine sequence analysis of the CR and vertebrate MRs and GRs, analysis of crystal structures of human MR and GR and data on transcriptional activation by 3-ketosteroids of wild-type and mutant MRs and GRs to investigate the evolution of selectivity for 3-ketosteroids by the MR in terrestrial vertebrates and ray-finned fish, as well as the basis for binding of some glucocorticoids by human MR and other vertebrate MRs.

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The role of ‘mineralocorticoids’ in teleost fish: Relative importance of glucocorticoid signaling in the osmoregulation and ‘central’ actions of mineralocorticoid receptor

Cited by 120 publications

References 54 publications

Principal function of mineralocorticoid signaling suggested by constitutive knockout of the mineralocorticoid receptor in medaka fish

Principal function of mineralocorticoid signaling suggested by constitutive knockout of the mineralocorticoid receptor in medaka fish

Interaction between the trout mineralocorticoid and glucocorticoid receptors in vitro

30 YEARS OF THE MINERALOCORTICOID RECEPTOR: Evolution of the mineralocorticoid receptor: sequence, structure and function

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