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Accepted Manuscript

Corticosteroid and progesterone transactivation of mineralocorticoid receptors from Amur sturgeon and tropical gar

Akira Sugimoto, Kaori Oka, Rui Sato, Shinji Adachi, Michael E Baker, Yoshinao Katsu
Biochemical Journal Aug 12, 2016, BCJ20160579; DOI: 10.1042/BCJ20160579
Akira Sugimoto
Department of Graduate School of Life Science, Hokkaido University, Sapporo, Japan
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Kaori Oka
Department of Graduate School of Life Science, Hokkaido University, Sapporo, Japan
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Rui Sato
Hokkaido University, Sapporo, Japan
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Shinji Adachi
Hokkaido University, Hakodate, Japan
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Michael E Baker
Medicine, University of California, San Diego, Dept. of Medicine, 0693, 9500 Gilman Drive, La Jolla, 92093-0693, United States
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  • For correspondence: mbaker@ucsd.edu
Yoshinao Katsu
Department of Graduate School of Life Science, Hokkaido University, Sapporo, Japan
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Abstract

The response to a panel of steroids by the mineralocorticoid receptor (MR) from Amur sturgeon and tropical gar, two basal ray-finned fish, expressed in HEK293 cells was investigated.  Half-maximal responses (EC50s) for transcriptional activation of sturgeon MR by 11-deoxycorticosterone, corticosterone, 11-deoxycortisol, cortisol and aldosterone, and progesterone were between 13 pM and 150 pM.  For gar MR, EC50s were between 8 pM and 55 pM.  Such low EC50s support physiological regulation by these steroids of the MR in sturgeon and gar.  Companion studies with human MR and zebrafish MR found higher EC50s compared to EC50s for sturgeon and gar MR, with EC50s for zebrafish MR closer to gar and sturgeon MR than was human MR.  For zebrafish MR, EC50s were between 75 pM and 740 pM; for human MR, EC50s were between 65 pM and 2 nM.  In addition to progesterone, spironolactone and 19nor-progesterone were agonists for all three fish MRs, in contrast to their antagonist activity for human MR, which is hypothesized to involve serine-810 in human MR because  all three steroids are agonists for a mutant human Ser810Leu-MR.  Paradoxically, sturgeon, gar and zebrafish MRs contain a serine corresponding to serine-810 in human MR.  Our data suggests alternative mechanism(s) for progesterone, spironolactone and 19nor-progesterone as MR agonists in these three ray-finned fishes and the need for caution in applying data for progesterone signaling in zebrafish to human physiology.

  • Amur sturgeon
  • tropical gar
  • mineralocorticoid receptor
  • corticosteroids
  • mineralocorticoid evolution
  • progesterone
  • ©2016 The Author(s)

This is an Accepted Manuscript; not the final Version of Record. Archiving permitted only in line with the archiving policy of Portland Press Limited. All other rights reserved.

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Corticosteroid and progesterone transactivation of mineralocorticoid receptors from Amur sturgeon and tropical gar
Akira Sugimoto, Kaori Oka, Rui Sato, Shinji Adachi, Michael E Baker, Yoshinao Katsu
Biochemical Journal Aug 2016, BCJ20160579; DOI: 10.1042/BCJ20160579
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Corticosteroid and progesterone transactivation of mineralocorticoid receptors from Amur sturgeon and tropical gar
Akira Sugimoto, Kaori Oka, Rui Sato, Shinji Adachi, Michael E Baker, Yoshinao Katsu
Biochemical Journal Aug 2016, BCJ20160579; DOI: 10.1042/BCJ20160579

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Keywords

Amur sturgeon
tropical gar
mineralocorticoid receptor
corticosteroids
mineralocorticoid evolution
progesterone

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