Glucocorticoid Receptor, but Not Mineralocorticoid Receptor, Mediates Cortisol Regulation of Epidermal Ionocyte Development and Ion Transport in Zebrafish (Danio Rerio)

• Published in: PloS one Vol. 8; no. 10; p. e77997
• Main Authors: Cruz, Shelly Abad, Lin, Chia-Hao, Chao, Pei-Lin, Hwang, Pung-Pung
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 2013; Public Library of Science (PLoS)
• Subjects: Aldosterone; Animals; Biology; Ca2+/H+-exchanging ATPase; Calcium; Calcium influx; Cell cycle; Cell Division - drug effects; Corticosteroid receptors; Corticosteroids; Cortisol; Danio rerio; Fish; Gene expression; Gills; Glucocorticoids; H+-transporting ATPase; Hormones; Humans; Hydrocortisone - pharmacology; Hydrogen; Ion transport; Ion Transport - drug effects; Keratinocytes; Localization; Mammals; Metabolism; Mucus; Na+/K+-exchanging ATPase; Oncorhynchus mykiss; Physiology; Receptors; Receptors, Glucocorticoid - genetics; Receptors, Glucocorticoid - metabolism; Receptors, Mineralocorticoid - genetics; Receptors, Mineralocorticoid - metabolism; Rodents; Secretion; Skin; Stem cells; Transcription; Trout; Zebrafish; Zebrafish Proteins - genetics; Zebrafish Proteins - metabolism; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0077997

Cortisol is the major endogenous glucocorticoid (GC) both in human and fish, mediated by corticosteroid receptors. Due to the absence of aldosterone production in teleost fish, cortisol is also traditionally accepted to function as mineralocorticoid (MC); but whether it acts through the glucocorticoid receptor (GR) or the mineralocorticoid receptor (MR) remains a subject of debate. Here, we used loss-of-function and rescue assays to determine whether cortisol affects zebrafish epidermal ionocyte development and function via the GR and/or the MR. GR knockdown morphants displayed a significant decrease in the major ionocytes, namely Na(+)-K(+)-ATPase-rich cells (NaRCs) and H(+)-ATPase-rich cells (HRCs), as well as other cells, including epidermal stem cells (ESCs), keratinocytes, and mucus cells; conversely, cell numbers were unaffected in MR knockdown morphants. In agreement, GR morphants, but not MR morphants, exhibited decreased NaRC-mediated Ca(2+) uptake and HRC-mediated H(+) secretion. Rescue via GR capped mRNA injection or exogenous cortisol incubation normalized the number of epidermal ionocytes in GR morphants. We also provide evidence for GR localization in epidermal cells. At the transcript level, GR mRNA is ubiquitously expressed in gill sections and present in both NaRCs and HRCs, supporting the knockdown and functional assay results in embryo. Altogether, we have provided solid molecular evidence that GR is indeed present on ionocytes, where it mediates the effects of cortisol on ionocyte development and function. Hence, cortisol-GR axis performs the roles of both GC and MC in zebrafish skin and gills.