Glucocorticoid receptors are involved in the regulation of pulsatile urea excretion in toadfish.

Department of Biology, McMaster University, Hamilton, Ontario L8S 4K1, Canada.
Journal of Comparative Physiology B (Impact Factor: 2.53). 12/2004; 174(8):649-58. DOI: 10.1007/s00360-004-0456-y
Source: PubMed

ABSTRACT The objectives of this study were to characterize the pattern of pulsatile urea excretion in the gulf toadfish in the wake of exogenous cortisol loading and to determine the receptors involved in the regulation of this mechanism. Toadfish were fitted with indwelling arterial catheters and were infused with isosmotic NaCl for 48 h after which fish were treated with cortisol alone, cortisol + peanut oil, cortisol + RU486 (a glucocorticoid receptor antagonist) or cortisol + spironolactone (a mineralocorticoid receptor antagonist). Upon cortisol loading, fish treated with cortisol alone, cortisol + oil or cortisol + spironolactone experienced a two- to threefold reduction in pulsatile urea excretion. This reduction was due to a decrease in urea pulse size with no effect on pulse frequency compared to values measured during the control NaCl infusion period. In addition, these fish showed an increase in plasma urea concentrations upon treatment. These apparent effects of cortisol treatment were abolished in fish treated with cortisol + RU486. In contrast, these fish showed an increase in pulsatile urea excretion mediated by a twofold increase in pulse size with no change in frequency. Likewise, fish treated with cortisol + RU486 showed a significant decrease in plasma urea concentrations over the course of the experiment. The findings of this study indicate that high levels of cortisol reduce pulsatile urea excretion by decreasing pulse size. In addition, it appears that glucocorticoid receptors and not mineralocorticoid receptors are involved in the regulation of the toadfish pulsatile urea excretion mechanism.

  • [Show abstract] [Hide abstract]
    ABSTRACT: In both mammals and teleost fish, serotonin stimulates cortisol secretion via the 5-HT(1A) receptor. Additionally, a negative feedback loop exists in mammals whereby increased circulating levels of cortisol inhibit 5-HT(1A) receptor activity. To investigate the possibility of such a feedback mechanism in teleosts, plasma cortisol levels and signaling in Gulf toadfish (Opsanus beta) were manipulated and the role of cortisol in the control of 5-HT(1A) evaluated. Despite a significant 4-fold increase in plasma [cortisol], crowded toadfish expressed similar amounts of 5-HT(1A) mRNA transcript as uncrowded toadfish; whereas, cortisol-implanted fish possessed 41.8% less 5-HT(1A) mRNA transcript compared to vehicle-implanted controls. This cortisol effect appeared to be reversed in RU486-injected fish, which blocks glucocorticoid receptors, as these fish expressed nearly twice as much 5-HT(1A) receptor transcript as the vehicle-injected fish despite significantly elevated cortisol levels. The binding affinity for the 5-HT(1A) receptor in the brain did not vary between any groups; however, maximum binding was significantly higher in uncrowded toadfish compared to crowded, and the same significant difference was observed between the maximum binding of vehicle and cortisol-implanted fish. The opposite trend was seen in RU486-injected and vehicle-injected fish, with RU486-injected fish having significantly higher maximal binding compared to vehicle-injected controls. Injection with the 5-HT(1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin revealed an inhibition of cortisol secretion that was independent of 5-HT(1A) transcript and protein binding. These results suggest that cortisol plays a role in regulating the 5-HT(1A) receptor via GR-mediated pathways; however, further study is necessary to elucidate how and where this inhibition is mediated.
    Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 01/2013; DOI:10.1016/j.cbpa.2013.01.014 · 2.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Stimulation of the serotonin 1A (5-HT1A) receptor subtype by 5-HT has been shown to result in an elevation in plasma corticosteroid levels in both mammals and several species of teleost fish, including the Gulf toadfish (Opsanus beta); however, in the case of teleost fish, it is not clearly known at which level of the hypothalamic-pituitary-interrenal axis the 5-HT1A receptor is stimulated. Additionally, previous investigations have revealed that chronic elevations of plasma cortisol mediate changes in brain 5-HT1A receptor mRNA and protein levels via the glucocorticoid receptor (GR); thus, we hypothesized that the function of centrally activated 5-HT1A receptors is reduced or abolished as a result of chronically elevated plasma cortisol levels and that this response is GR mediated. Our results are the first to demonstrate that intravenous injection of the 5-HT1A receptor agonist, 8-OH-DPAT, stimulates a significant increase in corticotropin-releasing factor (CRF) precursor mRNA expression in the hypothalamic region and the release of adrenocorticotropic hormone (ACTH) from the pituitary of teleost fish compared to saline-injected controls. We also provide evidence that cortisol, acting via GRs, attenuates the 5-HT1A receptor-mediated secretion of both CRF and ACTH.
    Journal of Comparative Physiology B 12/2013; DOI:10.1007/s00360-013-0793-9 · 2.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The goal of this study was to determine the relationship between cortisol and the toadfish serotonin 2A (5-HT2A ) receptor, which is believed to be responsible for the activation of the toadfish urea transporter, tUT. We hypothesize that elevations in cortisol would play a role in the regulation of the 5-HT2A receptor at the level of mRNA expression, ligand binding, and/or function. To test this idea, cortisol levels were manipulated by either crowding or through treatment with the cortisol synthesis blocker, metyrapone. Crowded fish had significantly higher circulating cortisol levels compared to uncrowded fish and cortisol levels in metyrapone-treated fish were significantly lower than saline-treated controls. No significant difference was measured in gill 5-HT2A mRNA expression levels between uncrowded and crowded, control- or metyrapone-treated fish. Furthermore, no significant difference was measured in [(3) H]-5-HT binding kinetics or in the competitive binding of the 5-HT2 agonist, α-methyl 5-HT, to isolated gill basolateral membranes of uncrowded or crowded toadfish. However, the binding maximum (Bmax ) of the 5-HT2A receptor antagonist, [(3) H]-ketanserin, was significantly different between all four groups of fish (metyrapone > control > crowded > uncrowded). Furthermore, metyrapone-treated fish excreted approximately twofold more urea compared to controls when injected with α-methyl 5-HT, a 5-HT2 receptor agonist shown to stimulate urea excretion. Our results suggest that cortisol may have differential effects on 5-HT receptor binding, which could have potential implications on the control of pulsatile urea excretion in toadfish. J. Exp. Zool. 9999A:1-12, 2013. © 2013 Wiley Periodicals, Inc.
    Journal of Experimental Zoology Part A Ecological Genetics and Physiology 06/2013; 319(5). DOI:10.1002/jez.1788 · 1.61 Impact Factor

Full-text (2 Sources)

Available from
Jun 2, 2014