Mineralocorticoid Receptors and Hormones: Fishing for Answers
http://www.100md.com
内分泌学杂志 2005年第1期
Department of Biology, University of Ottawa, Ottawa, Ontario, Canada K1N 6N5
Address all correspondence and requests for reprints to: K. M. Gilmour, Department of Biology, University of Ottawa, 150 Louis Pasteur, Ottawa, Ontario, Canada K1N 6N5. E-mail: katie.gilmour@science.uottawa.ca.
In tetrapod vertebrates, aldosterone is the main mineralocorticoid hormone, playing a key role in the regulation of sodium transport across epithelia. Metabolic functions are regulated by the glucocorticoid hormones cortisol and/or corticosterone. The mineralocorticoid and glucocorticoid hormones are produced by the adrenal cortex and exert their effects through separate, well-characterized receptors belonging to the superfamily of steroid hormone receptors that act as ligand-dependent transcription factors (1). By contrast, most fish appear to lack aldosterone; neither attempts to measure the hormone itself (2) nor attempts to find an enzyme with significant aldosterone synthesizing activity have been successful (3, 4). Cortisol is the principal corticosteroid produced by the interrenal tissue, the piscine equivalent of the adrenal cortex, and contributes to the regulation of salt and water balance as well as metabolism (5). Yet despite the apparent absence of a selective mineralocorticoid hormone, fish possess, as Sturm et al. report in this issue of Endocrinology (6), mineralocorticoid receptors (MRs). Their work reopens the debate about whether fish possess a mineralocorticoid hormone, while at the same time adding to a recent but growing body of evidence supporting the presence of multiple corticosteroid receptors in teleost fish (7, 8, 9).
Sturm et al. (6) cloned two MR isoforms from rainbow trout and examined their activation by various corticosteroids. As expected, cortisol was a potent agonist of the trout MRs, exhibiting EC50 values of 0.5–1.1 nM. This sensitivity to cortisol is similar to or greater than that of the trout glucocorticoid receptors (GRs), which exhibit EC50 values of 0.7–46 nM (9). A similar comparison has been made for only one other fish species, a cichlid, and here again the MR appears to be more sensitive to cortisol than the GRs (7). In this regard, the fish MRs parallel their mammalian counterparts, which are considered to be high-affinity cortisol receptors. Indeed, the high affinity of the mammalian MR for cortisol coupled with the approximately 100-fold higher circulating levels of glucocorticoids than aldosterone would result in continuous activation of MRs by cortisol were it not for the presence of a cellular sentinel that excludes cortisol from some MR-expressing cells. In the mammalian kidney, for example, MRs are coexpressed with the enzyme 11?-hydroxysteroid dehydrogenase type 2 (11?-HSD) which inactivates cortisol but not aldosterone, conferring selective activation by the mineralocorticoid hormone (10). Whether a similar protective mechanism exists in fish remains to be determined, but fish do at least possess the necessary enzyme (11) and a variety of tissues exhibit both MR and 11?-HSD gene expression (6, 7, 11).
If selective mineralocorticoid activation of the fish MR is in fact possible, what is the compound with selective mineralocorticoid action in fish? Sturm et al. (6) surveyed a number of corticosteroids and found that, in addition to aldosterone, 11-deoxycorticosterone was the most potent activator of the trout MRs; EC50 values for aldosterone and 11-deoxycorticosterone were about 10 times lower than those for cortisol. Like aldosterone, 11-deoxycorticosterone is a selective MR agonist: it does not activate the trout GR (9). Unlike the situation for aldosterone, however, the capacity to synthesize 11-deoxycorticosterone is present in fish (Fig. 1; Ref. 12) and, although data are sparse, the compound itself appears to be present in fish blood at levels that are not only measurable but are comparable to the concentrations required to activate the trout MR (13). In suggesting the potential for 11-deoxycorticosterone to function as a fish mineralocorticoid hormone, Sturm et al. (6) have presented an intriguing challenge to the research community. To establish 11-deoxycorticosterone as a physiologically significant fish MR ligand in vivo will require that changes in circulating 11-deoxycorticosterone levels occur in response to a relevant disturbance, and that physiological responses appropriate for the correction of that disturbance be initiated by 11-deoxycorticosterone administration. However, the physiological consequences of MR activation in fish have yet to be identified.
FIG. 1. Schematic of the probable pathways involved in cortisol and 11-deoxycorticosterone biosynthesis in fish. Solid black arrows indicate that the enzyme required for that step has been cloned in fish and displays appropriate activity (3 12 ); unfilled arrows indicate steps for which confirmation of enzyme activity is required. The gray arrow indicates that the enzyme required for that step has been cloned in fish but did not display the appropriate activity (12 ).
In mammals, MRs in the kidney are activated by aldosterone for the regulation of sodium retention, and hence salt and water balance (14). Aldosterone administration into fish, by contrast, appears to promote salt loss (15). Although this effect is the opposite of that in mammals, it does suggest that MRs play a role in electrolyte balance in fish. In fish, regulation of hydromineral balance relies on the integrated responses of the kidney and gills, unlike the situation in mammals, in which the kidneys predominate. Attempts to distinguish between kidney and gill responses suggested that mineralocorticoid administration promoted renal salt retention but branchial salt loss in rainbow trout—and, coincidentally, deoxycorticosterone acetate was the MR agonist used in these experiments (16). The direction of net sodium movement in fish depends on the salinity of the environment. Regardless of whether freshwater or marine environments are inhabited, the body fluids of teleost fish are maintained at an osmotic concentration that is about one third seawater strength. Freshwater fish counter the resultant water gain and ion loss by the copious production of dilute urine and by active salt uptake across the gills. Marine teleosts drink sea water to replace water losses and actively excrete the resultant salt load via the gills and kidney. Fish that move between these two environments (euryhaline species) arguably provide the most useful models for examining the hormonal control of salt and water balance.
Studies of such euryhaline species have revealed a key regulatory role for cortisol (5, 17). Cortisol levels increase when euryhaline fish are transferred from fresh water to sea water, and cortisol treatment improves salinity tolerance, in part by increasing the activity of a key element of the gill salt-secreting mechanism, Na+-K+-ATPase. However, parallel increases in salt uptake and the prevalence of ion transporting cells in the gills occur after cortisol treatment in freshwater fish. Additionally, transient increases in cortisol levels accompany transfer to more dilute environments. Thus, cortisol appears to be a piscine switch hitter, promoting salt secretion in sea water but salt uptake in fresh water (17). Interestingly, at least some of these mineralocorticoid actions of cortisol are mediated by GRs. Gill GR gene expression (18, 19) and numbers increase with seawater acclimation (20), and these changes translate into greater stimulation of Na+-K+-ATPase activity by cortisol (17). Also, the intestinal absorption of imbibed water that accompanies the transition from fresh water to sea water in developing salmon was inhibited by GR blockade (21). To what extent MRs are regulated by salinity changes remains to be determined, as do the osmoregulatory responses that are linked to MR activation. Indeed, unraveling the roles of GRs and MRs in the maintenance of salt and water balance in fish will require patience and ingenuity, given the suite of corticosteroid receptors that has been identified in two teleost fish (6, 7, 8, 9). This process must also take into consideration possible mechanisms, such as 11?-HSD, that may regulate access to the two receptor types. Finally, in light of the findings of Sturm et al. (6), a clear need exists to measure 11-deoxycorticosterone levels during osmoregulatory disturbances and to readdress the question of whether fish possess a selective mineralocorticoid hormone.
Fish MRs are broadly distributed beyond the tissues (such as gill; Fig. 2) that are important in salt and water balance. Interestingly, of the 12 rainbow trout tissues examined by Sturm et al. (6), MR mRNA levels were highest in brain. Brain was also the only cichlid tissue examined that displayed greater MR than GR gene expression (7). In mammals, MRs are found in the brain in the absence of 11?-HSD expression. Without the protective effect of 11?-HSD, brain MRs probably function as high-affinity cortisol receptors, but identifying the physiological roles of brain MRs vs. GRs is an ongoing challenge (22). Thus, investigating the physiological functions of fish MRs in nontraditional tissues is yet another item to add to the growing "to-do" list. In short order, corticosteroid signaling in fish has expanded from a one hormone-one receptor system to a system encompassing multiple receptor types (6, 7, 8, 9) and, given the findings of Sturm et al. (6), potentially multiple hormones. Additional fishing for answers will clearly be required to fully elucidate the complexity of this corticosteroid signaling system.
FIG. 2. Immunofluorescence localization of mineralocorticoid (MR) protein in the gills of rainbow trout (Oncorhynchus mykiss). A commercially available goat polyclonal antibody raised against the N-terminal region of the human MR together with an antigoat fluorescein isothiocyanate-conjugated secondary antibody were used to label trout gill sections (A). Nuclei were visualized using 4',6'-diamidino-2-phenylindole and are shown in overlay in blue. The specificity of the immunoreactivity is indicated by the absence of immunostaining in sections incubated without the primary antibody (B), or incubated with primary antibody in the presence of excess peptide against which the antibody was raised (C).[Figure courtesy of M. Bell, Department of Biology, University of Ottawa, Ottawa, Ontario, Canada.]
References
Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM 1995 Overview: the nuclear receptor superfamily: the second decade. Cell 83:835–839
Bern HA 1967 Hormones and endocrine glands of fishes. Science 158:455–462
Jiang J, Young G, Kobayashi T, Nagahama Y 1998 Eel (Anguilla japonica) testis 11?-hydroxylase gene is expressed in interrenal tissue and its product lacks aldosterone synthesizing activity. Mol Cell Endocrinol 146:207–211
Baker ME 2003 Evolution of glucocorticoid and mineralocorticoid responses: go fish. Endocrinology 144:4223–4225[Free Full Text]
Bern HA, Madsen SS 1992 A selective survey of the endocrine system of the rainbow trout (Oncorhynchus mykiss) with emphasis on the hormonal regulation of ion balance. Aquaculture 100:237–262
Sturm A, Bury NR, Dengreville L, Fagart J, Flouriot G, Rafestin-Oblin ME, Prunet P 2005 11-Deoxycorticosterone is a potent agonist of the rainbow trout (Oncorhynchus mykiss) mineralocorticoid receptor. Endocrinology 146:47–55
Greenwood AK, Butler PC, White RB, DeMarco U, Pearce D, Fernald RD 2003 Multiple corticosteroid receptors in a teleost fish: distinct sequences, expression patterns, and transcriptional activities. Endocrinology 144:4226–4236
Colombe L, Fostier A, Bury NR, Pakdel F, Guiguen Y 2000 A mineralocorticoid-like receptor in the rainbow trout, Oncorhynchus mykiss: cloning and characterization of its steroid binding domain. Steroids 65:319–328
Bury NR, Sturm A, Le Rouzic P, Lethimonier C, Ducouret B, Guiguen Y, Robinson-Rechavi M, Laudet V, Rafestin-Oblin ME, Prunet P 2003 Evidence for two distinct functional glucocorticoid receptors in teleost fish. J Mol Endocrinol 31:141–156
Funder JW, Pearce PT, Smith R, Smith AI 1988 Mineralocrticoid action: target tissue specificity is enzyme, not receptor, mediated. Science 242:583–585
Kusakabe M, Nakamura I, Young G 2003 11?-Hydroxysteroid dehydrogenase complementary deoxyribonucleic acid in rainbow trout: cloning, sites of expression, and seasonal changes in gonads. Endocrinology 144:2545
Li Y-Y, Inoue K, Takei Y 2003 Interrenal steroid 21-hydroxylase in eels: primary structure, progesterone-specific activity and enhanced expression by ACTH. J Mol Endocrinol 31:327–340
Campbell CM, Fostier A, Jalabert B, Truscott B 1980 Identification and quantification of steroids in the serum of rainbow trout during spermiation and oocyte maturation. J Endocrinol 85:371–378
Rogerson FM, Fuller PJ 2000 Mineralocorticoid action. Steroids 65:61–73
Homes WN, Butler DG 1963 The effect of adrenocortical steroids on the tissue electrolyte composition of the fresh-water rainbow trout (Salmo gairdneri). J Endocrinol 25:457–464
Homes WN 1959 Studies on the hormonal control of sodium metabolism in the rainbow trout (Salmo gairdneri). Acta Endocrinol (Copenh) 31:587–602
McCormick SD 2001 Endocrine control of osmoregulation in teleost fish. Am Zool 41:781–794
Uchida K, Kaneko T, Tagawa M, Hirano T 1998 Localization of cortisol receptor in branchial chloride cells in chum salmon fry. Gen Comp Endocrinol 109:175–185
Scott GR, Richards JG, Forbush B, Isenring P, Schulte PM 2004 Changes in gene expression in gills of the euryhaline killifish Fundulus heteroclitus after abrupt salinity transfer. Am J Physiol 287:C300–C309
Dean DB, Whitlow ZW, Borski RJ 2003 Glucocorticoid receptor upregulation during seawater adaptation in a euryhaline teleost, the tilapia (Oreochromis mossambicus). Gen Comp Endocrinol 132:112–118
Veillette PA, Sundell K, Specker JL 1995 Cortisol mediates the increase in intestinal fluid absorption in Atlantic salmon during parr-smolt transformation. Gen Comp Endocrinol 97:250–258
De Kloet ER 2004 Hormones and the stressed brain. Ann NY Acad Sci 1018:1–15(Kathleen M. Gilmour)
Address all correspondence and requests for reprints to: K. M. Gilmour, Department of Biology, University of Ottawa, 150 Louis Pasteur, Ottawa, Ontario, Canada K1N 6N5. E-mail: katie.gilmour@science.uottawa.ca.
In tetrapod vertebrates, aldosterone is the main mineralocorticoid hormone, playing a key role in the regulation of sodium transport across epithelia. Metabolic functions are regulated by the glucocorticoid hormones cortisol and/or corticosterone. The mineralocorticoid and glucocorticoid hormones are produced by the adrenal cortex and exert their effects through separate, well-characterized receptors belonging to the superfamily of steroid hormone receptors that act as ligand-dependent transcription factors (1). By contrast, most fish appear to lack aldosterone; neither attempts to measure the hormone itself (2) nor attempts to find an enzyme with significant aldosterone synthesizing activity have been successful (3, 4). Cortisol is the principal corticosteroid produced by the interrenal tissue, the piscine equivalent of the adrenal cortex, and contributes to the regulation of salt and water balance as well as metabolism (5). Yet despite the apparent absence of a selective mineralocorticoid hormone, fish possess, as Sturm et al. report in this issue of Endocrinology (6), mineralocorticoid receptors (MRs). Their work reopens the debate about whether fish possess a mineralocorticoid hormone, while at the same time adding to a recent but growing body of evidence supporting the presence of multiple corticosteroid receptors in teleost fish (7, 8, 9).
Sturm et al. (6) cloned two MR isoforms from rainbow trout and examined their activation by various corticosteroids. As expected, cortisol was a potent agonist of the trout MRs, exhibiting EC50 values of 0.5–1.1 nM. This sensitivity to cortisol is similar to or greater than that of the trout glucocorticoid receptors (GRs), which exhibit EC50 values of 0.7–46 nM (9). A similar comparison has been made for only one other fish species, a cichlid, and here again the MR appears to be more sensitive to cortisol than the GRs (7). In this regard, the fish MRs parallel their mammalian counterparts, which are considered to be high-affinity cortisol receptors. Indeed, the high affinity of the mammalian MR for cortisol coupled with the approximately 100-fold higher circulating levels of glucocorticoids than aldosterone would result in continuous activation of MRs by cortisol were it not for the presence of a cellular sentinel that excludes cortisol from some MR-expressing cells. In the mammalian kidney, for example, MRs are coexpressed with the enzyme 11?-hydroxysteroid dehydrogenase type 2 (11?-HSD) which inactivates cortisol but not aldosterone, conferring selective activation by the mineralocorticoid hormone (10). Whether a similar protective mechanism exists in fish remains to be determined, but fish do at least possess the necessary enzyme (11) and a variety of tissues exhibit both MR and 11?-HSD gene expression (6, 7, 11).
If selective mineralocorticoid activation of the fish MR is in fact possible, what is the compound with selective mineralocorticoid action in fish? Sturm et al. (6) surveyed a number of corticosteroids and found that, in addition to aldosterone, 11-deoxycorticosterone was the most potent activator of the trout MRs; EC50 values for aldosterone and 11-deoxycorticosterone were about 10 times lower than those for cortisol. Like aldosterone, 11-deoxycorticosterone is a selective MR agonist: it does not activate the trout GR (9). Unlike the situation for aldosterone, however, the capacity to synthesize 11-deoxycorticosterone is present in fish (Fig. 1; Ref. 12) and, although data are sparse, the compound itself appears to be present in fish blood at levels that are not only measurable but are comparable to the concentrations required to activate the trout MR (13). In suggesting the potential for 11-deoxycorticosterone to function as a fish mineralocorticoid hormone, Sturm et al. (6) have presented an intriguing challenge to the research community. To establish 11-deoxycorticosterone as a physiologically significant fish MR ligand in vivo will require that changes in circulating 11-deoxycorticosterone levels occur in response to a relevant disturbance, and that physiological responses appropriate for the correction of that disturbance be initiated by 11-deoxycorticosterone administration. However, the physiological consequences of MR activation in fish have yet to be identified.
FIG. 1. Schematic of the probable pathways involved in cortisol and 11-deoxycorticosterone biosynthesis in fish. Solid black arrows indicate that the enzyme required for that step has been cloned in fish and displays appropriate activity (3 12 ); unfilled arrows indicate steps for which confirmation of enzyme activity is required. The gray arrow indicates that the enzyme required for that step has been cloned in fish but did not display the appropriate activity (12 ).
In mammals, MRs in the kidney are activated by aldosterone for the regulation of sodium retention, and hence salt and water balance (14). Aldosterone administration into fish, by contrast, appears to promote salt loss (15). Although this effect is the opposite of that in mammals, it does suggest that MRs play a role in electrolyte balance in fish. In fish, regulation of hydromineral balance relies on the integrated responses of the kidney and gills, unlike the situation in mammals, in which the kidneys predominate. Attempts to distinguish between kidney and gill responses suggested that mineralocorticoid administration promoted renal salt retention but branchial salt loss in rainbow trout—and, coincidentally, deoxycorticosterone acetate was the MR agonist used in these experiments (16). The direction of net sodium movement in fish depends on the salinity of the environment. Regardless of whether freshwater or marine environments are inhabited, the body fluids of teleost fish are maintained at an osmotic concentration that is about one third seawater strength. Freshwater fish counter the resultant water gain and ion loss by the copious production of dilute urine and by active salt uptake across the gills. Marine teleosts drink sea water to replace water losses and actively excrete the resultant salt load via the gills and kidney. Fish that move between these two environments (euryhaline species) arguably provide the most useful models for examining the hormonal control of salt and water balance.
Studies of such euryhaline species have revealed a key regulatory role for cortisol (5, 17). Cortisol levels increase when euryhaline fish are transferred from fresh water to sea water, and cortisol treatment improves salinity tolerance, in part by increasing the activity of a key element of the gill salt-secreting mechanism, Na+-K+-ATPase. However, parallel increases in salt uptake and the prevalence of ion transporting cells in the gills occur after cortisol treatment in freshwater fish. Additionally, transient increases in cortisol levels accompany transfer to more dilute environments. Thus, cortisol appears to be a piscine switch hitter, promoting salt secretion in sea water but salt uptake in fresh water (17). Interestingly, at least some of these mineralocorticoid actions of cortisol are mediated by GRs. Gill GR gene expression (18, 19) and numbers increase with seawater acclimation (20), and these changes translate into greater stimulation of Na+-K+-ATPase activity by cortisol (17). Also, the intestinal absorption of imbibed water that accompanies the transition from fresh water to sea water in developing salmon was inhibited by GR blockade (21). To what extent MRs are regulated by salinity changes remains to be determined, as do the osmoregulatory responses that are linked to MR activation. Indeed, unraveling the roles of GRs and MRs in the maintenance of salt and water balance in fish will require patience and ingenuity, given the suite of corticosteroid receptors that has been identified in two teleost fish (6, 7, 8, 9). This process must also take into consideration possible mechanisms, such as 11?-HSD, that may regulate access to the two receptor types. Finally, in light of the findings of Sturm et al. (6), a clear need exists to measure 11-deoxycorticosterone levels during osmoregulatory disturbances and to readdress the question of whether fish possess a selective mineralocorticoid hormone.
Fish MRs are broadly distributed beyond the tissues (such as gill; Fig. 2) that are important in salt and water balance. Interestingly, of the 12 rainbow trout tissues examined by Sturm et al. (6), MR mRNA levels were highest in brain. Brain was also the only cichlid tissue examined that displayed greater MR than GR gene expression (7). In mammals, MRs are found in the brain in the absence of 11?-HSD expression. Without the protective effect of 11?-HSD, brain MRs probably function as high-affinity cortisol receptors, but identifying the physiological roles of brain MRs vs. GRs is an ongoing challenge (22). Thus, investigating the physiological functions of fish MRs in nontraditional tissues is yet another item to add to the growing "to-do" list. In short order, corticosteroid signaling in fish has expanded from a one hormone-one receptor system to a system encompassing multiple receptor types (6, 7, 8, 9) and, given the findings of Sturm et al. (6), potentially multiple hormones. Additional fishing for answers will clearly be required to fully elucidate the complexity of this corticosteroid signaling system.
FIG. 2. Immunofluorescence localization of mineralocorticoid (MR) protein in the gills of rainbow trout (Oncorhynchus mykiss). A commercially available goat polyclonal antibody raised against the N-terminal region of the human MR together with an antigoat fluorescein isothiocyanate-conjugated secondary antibody were used to label trout gill sections (A). Nuclei were visualized using 4',6'-diamidino-2-phenylindole and are shown in overlay in blue. The specificity of the immunoreactivity is indicated by the absence of immunostaining in sections incubated without the primary antibody (B), or incubated with primary antibody in the presence of excess peptide against which the antibody was raised (C).[Figure courtesy of M. Bell, Department of Biology, University of Ottawa, Ottawa, Ontario, Canada.]
References
Mangelsdorf DJ, Thummel C, Beato M, Herrlich P, Schutz G, Umesono K, Blumberg B, Kastner P, Mark M, Chambon P, Evans RM 1995 Overview: the nuclear receptor superfamily: the second decade. Cell 83:835–839
Bern HA 1967 Hormones and endocrine glands of fishes. Science 158:455–462
Jiang J, Young G, Kobayashi T, Nagahama Y 1998 Eel (Anguilla japonica) testis 11?-hydroxylase gene is expressed in interrenal tissue and its product lacks aldosterone synthesizing activity. Mol Cell Endocrinol 146:207–211
Baker ME 2003 Evolution of glucocorticoid and mineralocorticoid responses: go fish. Endocrinology 144:4223–4225[Free Full Text]
Bern HA, Madsen SS 1992 A selective survey of the endocrine system of the rainbow trout (Oncorhynchus mykiss) with emphasis on the hormonal regulation of ion balance. Aquaculture 100:237–262
Sturm A, Bury NR, Dengreville L, Fagart J, Flouriot G, Rafestin-Oblin ME, Prunet P 2005 11-Deoxycorticosterone is a potent agonist of the rainbow trout (Oncorhynchus mykiss) mineralocorticoid receptor. Endocrinology 146:47–55
Greenwood AK, Butler PC, White RB, DeMarco U, Pearce D, Fernald RD 2003 Multiple corticosteroid receptors in a teleost fish: distinct sequences, expression patterns, and transcriptional activities. Endocrinology 144:4226–4236
Colombe L, Fostier A, Bury NR, Pakdel F, Guiguen Y 2000 A mineralocorticoid-like receptor in the rainbow trout, Oncorhynchus mykiss: cloning and characterization of its steroid binding domain. Steroids 65:319–328
Bury NR, Sturm A, Le Rouzic P, Lethimonier C, Ducouret B, Guiguen Y, Robinson-Rechavi M, Laudet V, Rafestin-Oblin ME, Prunet P 2003 Evidence for two distinct functional glucocorticoid receptors in teleost fish. J Mol Endocrinol 31:141–156
Funder JW, Pearce PT, Smith R, Smith AI 1988 Mineralocrticoid action: target tissue specificity is enzyme, not receptor, mediated. Science 242:583–585
Kusakabe M, Nakamura I, Young G 2003 11?-Hydroxysteroid dehydrogenase complementary deoxyribonucleic acid in rainbow trout: cloning, sites of expression, and seasonal changes in gonads. Endocrinology 144:2545
Li Y-Y, Inoue K, Takei Y 2003 Interrenal steroid 21-hydroxylase in eels: primary structure, progesterone-specific activity and enhanced expression by ACTH. J Mol Endocrinol 31:327–340
Campbell CM, Fostier A, Jalabert B, Truscott B 1980 Identification and quantification of steroids in the serum of rainbow trout during spermiation and oocyte maturation. J Endocrinol 85:371–378
Rogerson FM, Fuller PJ 2000 Mineralocorticoid action. Steroids 65:61–73
Homes WN, Butler DG 1963 The effect of adrenocortical steroids on the tissue electrolyte composition of the fresh-water rainbow trout (Salmo gairdneri). J Endocrinol 25:457–464
Homes WN 1959 Studies on the hormonal control of sodium metabolism in the rainbow trout (Salmo gairdneri). Acta Endocrinol (Copenh) 31:587–602
McCormick SD 2001 Endocrine control of osmoregulation in teleost fish. Am Zool 41:781–794
Uchida K, Kaneko T, Tagawa M, Hirano T 1998 Localization of cortisol receptor in branchial chloride cells in chum salmon fry. Gen Comp Endocrinol 109:175–185
Scott GR, Richards JG, Forbush B, Isenring P, Schulte PM 2004 Changes in gene expression in gills of the euryhaline killifish Fundulus heteroclitus after abrupt salinity transfer. Am J Physiol 287:C300–C309
Dean DB, Whitlow ZW, Borski RJ 2003 Glucocorticoid receptor upregulation during seawater adaptation in a euryhaline teleost, the tilapia (Oreochromis mossambicus). Gen Comp Endocrinol 132:112–118
Veillette PA, Sundell K, Specker JL 1995 Cortisol mediates the increase in intestinal fluid absorption in Atlantic salmon during parr-smolt transformation. Gen Comp Endocrinol 97:250–258
De Kloet ER 2004 Hormones and the stressed brain. Ann NY Acad Sci 1018:1–15(Kathleen M. Gilmour)