title: In-vivo regulation of Krüppel-like factor 9 by corticosteroids and their receptors across tissues in tadpoles of Xenopus tropicalis.
abstract: Corticosteroids are critical for normal development and for mediating effects of stress during development in all vertebrates. Even though gene knockout studies in mouse and zebrafish have identified a number of developmental roles of corticosteroids and their receptors, the numerous pleiotropic actions of these hormones affecting various aspects of development are understudied. For the most part, neither the endogenous hormone(s) nor their receptor(s) regulating developmental processes during natural development have been determined. Here, we address this issue by elucidating the endogenous regulation of the transcription factor Krüppel-like factor 9 (klf9) across tissues during development by corticosteroid hormones (aldosterone and corticosterone) and their nuclear receptors (type-I and type-II receptors). First, we measured the developmental expression profiles of klf9 and type-I and type-II corticosteroid receptors in key target tissues, brain, lungs, and tail, during larval and metamorphic stages in Xenopus tropicalis. We also studied the corticosteroid regulation of klf9 in these tissues in-vivo using exogenous hormone treatments and receptor antagonists. Klf9 and the corticosteroid receptors were expressed in each tissue and significantly increased in expression reaching a peak at metamorphic climax, except for the type-II receptor in brain and tail whose expression did not change significantly across stages. Both corticosteroid hormones induced klf9 in each tissue, although aldosterone required a five times higher dose than corticosterone to cause a significant induction. The upregulation of klf9 by both corticosteroids was completely blocked by the use of the type-II receptor antagonist RU486 and not the type-I receptor antagonist spironolactone. These results are consistent with previous in-vitro studies and indicate for the first time in-vivo that corticosteroid regulation of klf9 occurs exclusively via corticosterone and type-II receptor interaction across tissues.
authors.affiliation: Department of Biological Sciences, University of Cincinnati, 312 Clifton Court, Cincinnati, OH 45221, USA.
authors.forename: Leena H
authors.initials: LH
authors.lastname: Shewade
authors.affiliation: Department of Biological Sciences, University of Cincinnati, 312 Clifton Court, Cincinnati, OH 45221, USA.
authors.forename: Katelin A
authors.initials: KA
authors.lastname: Schneider
authors.affiliation: Department of Biological Sciences, University of Cincinnati, 312 Clifton Court, Cincinnati, OH 45221, USA.
authors.forename: Audrey C
authors.initials: AC
authors.lastname: Brown
authors.affiliation: Department of Biological Sciences, University of Cincinnati, 312 Clifton Court, Cincinnati, OH 45221, USA. Electronic address: buchhodr@ucmail.uc.edu.
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Buchholz
mesh_terms: D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D007814:Larva / Q000187:drug effects / Q000235:genetics; D008297:Male; D051379:Mice; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013997:Time Factors; D014981:Xenopus / Q000378:metabolism*; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051741:Kruppel-Like Transcription Factors; D011987:Receptors, Steroid; D029867:Xenopus Proteins; D000450:Aldosterone; D003345:Corticosterone
keywords: Aldosterone; Amphibian metamorphosis; Corticosterone; Glucocorticoid receptor; Mineralocorticoid receptor; RU486; Spironolactone