The amino-terminal A/B domain is quite variable among species and is important in modulating transcriptional activity. The mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR) are members of the steroid/thyroid/retinoid receptor superfamily and share a canonical structure comprised of distinct functional domains ( 4). The effects of corticosteroid hormones are mediated through two related intracellular receptors that act as ligand-dependant transcription factors. In addition to its primary role in the kidney, aldosterone is involved in the regulation of blood pressure, perspiration, and salt taste sensitivity ( 3). It is now known that glucocorticoids also mediate the stress response, play important roles in cognition, act as immune suppressants and antiinflammatories, and mediate some processes traditionally thought to depend on mineralocorticoids, such as salt balance ( 2).
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Glucocorticoids, including cortisol and corticosterone, were identified for their role in liver glycogen deposition, whereas the mineralocorticoids, predominantly aldosterone, were recognized to regulate mineral balance principally by controlling sodium retention in the kidney ( 1). These corticosteroid hormones, the glucocorticoids and the mineralocorticoids, were originally named for their distinct bodily functions in mammals. The cortex of the adrenal gland secretes two classes of corticosteroid hormones that modulate functions, such as glucose metabolism, mineral balance, and behavior. STEROID HORMONES ARE essential for the regulation of a wide variety of physiological processes. The identification of four CR subtypes in teleosts suggests a more complicated corticosteroid signaling in fish than previously recognized. Additionally, the two HbGR2 isoforms were expressed uniquely in different tissues and were functionally distinct in their actions on classical GR-sensitive promoters.
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Trans-activation assays demonstrated that the CRs were selective for corticosteroid hormones and showed that the HbMR was similar to mammalian MRs in being more sensitive to both cortisol and aldosterone than the GRs. Quantitative PCR revealed differential patterns of CR tissue expression in organs dependent on corticosteroid action. Sequence comparison and phylogenetic analysis showed that these CRs sort naturally into GR and MR groups, and that the GR duplication we describe will probably be common to all teleosts. Here we describe the characterization of four CRs in a cichlid fish, Haplochromis burtoni: a previously undescribed GR (HbGR1), another GR expressed in two splice isoforms (HbGR2a and HbGR2b), and an MR (HbMR). In fish, the overlap in processes controlled by CRs may be different from that in other vertebrates, as fish are thought to synthesize only glucocorticoids, whereas they express both GR and MR. There is substantial overlap in the binding of these two receptor types to hormones and to DNA.
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These hormones act through two classes of corticosteroid receptors (CR) that are ligand-dependent transcription factors: type I or mineralocorticoid receptor (MR) and type II or glucocorticoid receptor (GR). Corticosteroid hormones, including the mineralocorticoids and the glucocorticoids, regulate diverse physiological functions in vertebrates.