© 2000 by The Society for Integrative and Comparative Biology
Endocrine Disruptors of the Stress Axis in Natural Populations: How Can We Tell?1
1 Department of Environmental, Population and Organismic Biology, Campus Box 334, University of Colorado, Boulder, Colorado 80309-0334
 |
SYNOPSIS |
|---|
TOP
 SYNOPSIS INTRODUCTIONTHE NEUROENDOCRINE STRESS...THE STRESS AXIS OF...BROWN TROUT AND METAL...WHERE DO WE GO...REFERENCES |
|---|
Often, as environmental endocrinologists, we observe animals in nature with the goal of describing their normal endocrinology. However, the contamination of virtually all natural habitats by chemicals of anthropogenic origins (e.g., PCBs, organochlorines, phytoestrogens, alkyphenols, heavy metals) that might alter endocrine conditions suggests we need to reevaluate many of our field studies with respect to points of reference or controls. The impaired response of the stress axis of feral brown trout, Salmo trutta, correlated with chronic exposure to heavy metals is examined as a case in point although the problems extend to other hypothalamic axes as well. Our studies emphasize that measurement of one static endocrine parameter to assess the health of any hypothalamus-pituitary axis (e.g., plasma cortisol levels to indicate stress) should not be used as a biomarker for field studies.
|
INTRODUCTION |
|---|
|
TOP
SYNOPSISINTRODUCTIONTHE NEUROENDOCRINE STRESS...THE STRESS AXIS OF...BROWN TROUT AND METAL...WHERE DO WE GO...REFERENCES |
|---|
Comparative endocrinologists often attempt to describe the roles of neuroendocrine and endocrine factors related to major life history events such as development, sexual maturation, and reproduction while observing animals in their natural habitats. The integration of endocrinology with behavior, ecology, and other aspects of physiology of animals is viewed with an evolutionary perspective. Because of a preoccupation with environmental factors that influence neuroendocrine axes and a focus on major life history, these scientists often are called "environmental endocrinologists." In contrast to this orientation, some comparative endocrinologists study non-mammalian vertebrates or invertebrate animals as model systems in which to unravel basic mechanisms of endocrine function that could shed light on processes in other taxa including humans. Irrespective of our focus, most comparative endocrinologists have a sense that understanding of endocrine systems should tell us something about how animals function in nature and how these mechanisms may have evolved.
Endocrine-disrupting chemicals (EDCs; also called xenobiotics) could disrupt natural systems in several ways. They may act by mimicking or inhibiting the actions of a hormone through interaction with its receptor and mechanism of action, by altering synthesis of a hormone or its receptor, or by altering the rate of metabolism and/or excretion of the hormone. The first wide-spread recognition of an EDC was the association of the estrogenic pesticide DDT with reproductive failure in birds (see Colborn et al., 1996
; McLachlan and Arnold, 1996). The banning of the use of DDT in the USA was followed by a marked recovery among the threatened avian species. The discovery of DDT effects on reproduction and the ban of its use was paralleled by the demonstration of the cancer-inducing actions of a powerful synthetic estrogen, diethylstilbestrol (DES), and its discontinued clinical use in humans (see review by Newbold, 1999). In spite of these events, many comparative endocrinologists continued their field studies as before.
Within the past 10 years have come dramatic reports of feminization of fishes by sewage effluents (Mattheisson, 1998; Mattheisson and Sumpter, 1998), development of imposexes in gastropod mollusks (Fent, 1996) and disruption of normal sexual development in male alligators by chemical pollution (e.g., Guillette et al., 1996), impaired reproductive function in birds following accumulation of polychlorinated biphenyls (PCBs) (see Feyk and Giesy, 1998), decreased immunological function in seals (see Ross et al., 1996), and reductions in number and percent motility of human sperm (see Swan et al., 1997; Toppari and Skakkebaek, 2000). These and other reports of impairment in endocrine functions (i.e., endocrine disruption) allegedly attributed to many of the hundreds of anthropogenic chemicals ranging from alkyphenols to zinc that are accumulating in our environment (e.g., see Colburn et al., 1996; Kendall, R. et al., 1998). Whether willing or unwilling, comparative/environmental endocrinologists now are participants in the new discipline of ecotoxicology (Banks and Stark, 1998), and they must acknowledge the potential impact of EDCs on the animals they study. It is suggested that there is no threshold level (no effect level, NOEL) for any chemical that mimics the action of a natural hormone (see Sheehan et al., 1999). So, in our studies of wild animals, how can we be sure that we are studying natural roles of adrenal, thyroid, or gonadal hormones and not those that have been altered in some way by EDCs? It is clear that we need a standard for comparison, but what shall we use? In the following discussion, I will address this question, using the neuroendocrine stress axis of wild vertebrates, specifically teleostean fishes.
|
THE NEUROENDOCRINE STRESS RESPONSE IN VERTEBRATES |
|---|
|
TOP
SYNOPSISINTRODUCTIONTHE NEUROENDOCRINE STRESS...THE STRESS AXIS OF...BROWN TROUT AND METAL...WHERE DO WE GO...REFERENCES |
|---|
The response of the neuroendocrine stress axis of vertebrates, and especially teleostean fishes, illustrates the problems we now face. (Amphibian responses to stress have been studied by Mendonça, unpublished). Although there is considerable debate as to what constitutes stress, and most definitions appear to be somewhat vague (Levine and Ursin, 1991
; Weiner, 1991), most researchers concede that a stressor is a factor that disturbs the natural homeostatic balance within an organism and produces general stress as well as specific responses to a stressor (see Chrousos, 1997). Furthermore, chronic stress may produce predictable secondary alterations in the physiology of animals (Fig. 1).
|
The neuroendocrine stress axis in vertebrates is the hypothalamus-pituitary-adrenocortical (HPA) axis. The alternative name, hypothalamus-pituitary-interrenal (HPI) axis, frequently is applied to teleosts in which the interrenal gland is homologous to the adrenocortical cells of mammals (see Norris, 1997
; Sumpter, 1997). The term "interrenal" may be applied to amphibians as well. In addition, the sympathetic nervous system also participates initially in the stress response through the release of epinephrine or norepinephrine from the adrenal medulla or its homologue in many non-mammals (chromaffin tissue). Since this discussion emphasizes chronic rather than acute stress, only the involvement of the HPA axis will be considered.
The following general description of the HPA axis in vertebrates is based on reviews by Norris (1997) and Norman and Litwack (1998). Specifically, in response to signals from higher brain centers the hypothalamus of fishes and tetrapods secretes neuropeptides that regulate pituitary secretion. The major hypothalamic regulating neuropeptide is corticotropin-releasing hormone (CRH) which stimulates the synthesis and release of corticotropin (ACTH) by the pituitary gland into the blood. ACTH in turn causes the adrenocortical (interrenal) cells to secrete the glucocorticoids, cortisol and/or corticosterone. Glucocorticoids also exhibit negative feedback on the HPA axis, especially at the level of the hypothalamus (see Herman and Cullinan, 1997) and can influence CRH and ACTH secretion. In addition, prolonged elevation of glucocorticoids can bring about a partial or complete repression of reproductive function, reduction in body weight, and impairment of the immune response system (Fig. 1) through a variety of mechanisms. Thus, it is important to understand the status of the HPA axis in vertebrates before attempting to interpret reproductive status, growth, or general health of a population. A similar argument may be made for the hypothalamus-pituitary-thyroid (HPT) axis, too, since hypothyroidism typically is associated with reduced reproductive performance in all vertebrates as well as reduced adrenocortical function.
|
THE STRESS AXIS OF TELEOSTS |
|---|
|
TOP
SYNOPSISINTRODUCTIONTHE NEUROENDOCRINE STRESS...THE STRESS AXIS OF...BROWN TROUT AND METAL...WHERE DO WE GO...REFERENCES |
|---|
Although cortisol is termed a glucocorticoid in mammals because of its role in carbohydrate metabolism (e.g., gluconeogenesis), it functions in teleosts as both a glucocorticoid and a mineralocorticoid (see Norris, 1997
). Thus, the major actions of cortisol in fishes are the regulation of ion balance in the gills as well as metabolic actions on liver and muscle that direct nutrients to the central nervous system.
In many studies of fishes, investigators interpret an elevation in plasma levels of cortisol following exposure to a stressor as a biomarker to indicate that an animal is under acute or chronic stress (Barton, 1997; Barton and Iwama, 1991; Sumpter, 1997). In nature, one also has to take into account daily and seasonal rhythms in basal corticosteroid secretion in the experimental design. For example, circulating cortisol levels and the stress response are influenced in trout by reproductive state and gonadal steroids (Bry, 1985; Pickering and Christie, 1981; Pottinger et al., 1995, 1996). However, using a simple elevation in cortisol as evidence of stress may be misleading in teleosts as well as in other vertebrates. Many studies have demonstrated that application of a stressor may cause only a transient increase in cortisol followed by a return to baseline or the pre-stress level; for example, acclimation of a freshwater trout to sea water (Dickhoff et al., 1990). Furthermore, fishes are extremely sensitive to a wide variety of stressors (Table 1) and can exhibit marked increases in cortisol within a few minutes following exposure to a stressor such as handling or confinement (Table 2; see also review by Barton and Iwama, 1991) or electroshock (Barton and Grosh, 1996). Consequently, it is difficult to obtain true baseline data on cortisol levels for fishes in the field. These same problems may exist for other vertebrates as well.
|
|
BROWN TROUT AND METAL POLLUTION |
|---|
|
TOP
SYNOPSISINTRODUCTIONTHE NEUROENDOCRINE STRESS...THE STRESS AXIS OF...BROWN TROUT AND METAL...WHERE DO WE GO...REFERENCES |
|---|
Studies on feral populations of brown trout, Salmo trutta, in Colorado streams polluted with heavy metals led us to suspect that brown trout living in contaminated regions of the river (chronic exposure) were under greater stress than fish living upstream in cleaner water. The metals closest to toxic (lethal) thresholds in these waters typically are cadmium (Cd) and zinc (Zn) (Davies, 1989
; Brown et al., 1994). In particular, Cd acts as an endocrine disruptor in vertebrates (see Keith, 1997). Cd, for example, alters the sensitivity of pituitary gonadotropes to hypothalamic gonadotropin-releasing hormone (GnRH) in Atlantic croaker, Micropogonias undulatus (Thomas, 1989; Thomas and Wofford, 1993), decreases levels of glucocorticoid-dependent gluconeogenic enzymes (Mounib et al., 1976), and affects the responsiveness of adrenocortical tissue to ACTH in yellow perch, Perca flavescens and rainbow trout, Oncorhynchus mykiss (Brodeur et al., 1997; Hontela, 1997; Hontela et al., 1995).
Woodling (1993) collected brown trout living in metal-contaminated water of the Arkansas River and transferred them to cages located upstream in a toxic site where no fish could live because of the lethal levels of metals, primarily Cd and Zn, entering the river at that point. He also transported comparable trout from an uncontaminated (clean) site located upstream from the toxic site to cages in the toxic site. Reciprocal transfers were made to control for capture, handling, and placing fish in cages (fish from the clean site placed in cages at the contaminated site downstream of the toxic site; downstream fish to the clean site, etc.). According to laboratory data (Anadu et al., 1989; Hobson and Birge, 1989; Kito et al., 1982; Pascoe and Beattie, 1979; Sinley et al., 1974), fish previously exposed to Cd or Zn (i.e., the downstream brown trout) should be more resistant to a lethal dose of metals (i.e., the toxic site) than fish previously unexposed to metals (i.e., brown trout from the clean site). Unexpectedly, the fish collected downstream were the first to die in the toxic site. Eventually, all of the fish in the toxic site died, but none of the fish transplanted to other river sites died. Duplication of this experiment on another contaminated river, Clear Creek, yielded similar results (Woodling, 1993). Chronic exposure of fish to metals provided them no special resistance but instead seemed to make them more susceptible to the toxic effects of these pollutants.
To test the hypothesis that the stress response mechanisms of brown trout chronically exposed to metals is compromised, we employed radioimmunoassay to measure baseline cortisol levels of brown trout in blood plasma taken immediately after electroshocking the fish in the Eagle River (Norris et al., 1997, 1999) and in Clear Creek (Norris et al., unpublished data using same protocols as for the Eagle River). There were no differences in basal plasma cortisol levels between fish living in clean water and those living in contaminated regions of these rivers several miles downstream (Table 3). However, histological examination of adrenocortical tissue from Eagle River fish from the contaminated site revealed evidence of chronic stimulation by ACTH as well as increased numbers of CRH-immunoreactive cells in the hypothalamus (Norris et al., 1997). These results suggested to us that the hypothalamus and pituitary glands, and possibly the adrenocortical tissue, of these metal-exposed fish are hypersecreting to maintain similar "baseline" cortisol levels.
|
Many studies have established that acute or long-term confinement of salmonids is sufficient to elevate plasma cortisol levels (see Table 1). These levels can remain elevated for as long as 24 hr or more after an acute episode of capture and confinement (Pickering et al., 1987
; Pottinger and Mosuwe, 1994; Pottinger et al., 1987). Brown trout not pre-exposed to metals but confined for 24 hr were able to maintain the initial stress response for at least 24 hr (Pottinger et al., 1995). Therefore, we decided to subject fish from metal-contaminated and uncontaminated sites in the Eagle River to a 24-hr severe confinement stress (Wedemeyer et al., 1990) to see if their HPA axes would respond in a similar manner. We observed a delayed response in cortisol secretion by brown trout from the contaminated site following one hour of confinement in spite of higher plasma levels of ACTH (Norris et al., 1999). Although there was no difference in plasma cortisol following 3 hours of confinement, plasma levels of ACTH were significantly higher in fish from the contaminated site at that time. Finally, fish chronically exposed to contaminated water could not maintain elevated ACTH and cortisol both of which decreased significantly between 12 and 24 hr of confinement (Figs. 2, 3).
|
|
Although these data from the Eagle River are correlative and do not demonstrate a cause-effect relationship between higher metal concentrations and disruption of the HPA axis, there is evidence from other studies to support the possible action of Cd on the HPA axis of brown trout. However, independent or synergistic influences of Zn or even other metals can not be ruled out completely since there are no comparable data like the Cd studies in fish. Cd may act at the level of the adrenocortical cells, causing them to be less responsive to ACTH. Evidence for an adrenocortical site of action is supported by failure of yellow perch chronically exposed to Cd to respond normally to injections of ACTH (Hontela, 1997
). Accelerated metabolism of cortisol by the liver and/or elevated kidney clearance of cortisol following chronic exposure to metals could increase CRH and ACTH secretion through normal feedback pathways. Because of adrenocortical insensitivity, chronically exposed brown trout appear to maintain elevated hypothalamic and pituitary activity to achieve baseline cortisol, leaving them little reserve to deal with a severe stress such as collection/confinement (Norris et al., 1999) or collection/confinement/toxic chemical exposure (Woodling, 1993). If elevated cortisol is a mechanism to maintain homeostasis when faced with a stressor, fish chronically exposed to heavy metals are clearly disadvantaged. They must secrete more CRH and ACTH in order to maintain a baseline level of cortisol, and, when challenged with a severe stressor, the HPA axis cannot maintain an optimal stress response. |
WHERE DO WE GO FROM HERE? |
|---|
|
TOP
SYNOPSISINTRODUCTIONTHE NEUROENDOCRINE STRESS...THE STRESS AXIS OF...BROWN TROUT AND METAL...WHERE DO WE GO...REFERENCES |
|---|
In one way, we were extremely fortunate to have chosen brown trout for this study because they are relatively sedentary, especially at the size we studied (about 25 cm mean total length; Young, 1994
). The fidelity of these fish to a specific site was supported by the significantly higher levels of metals present in the kidneys of fish from the contaminated sites (see Norris et al., 1999). Had we chosen to examine rainbow trout, which move considerable distances in relatively short periods of time, we might have missed the site-based influences of metals and perhaps had no clue as to their endocrine disrupting potential.
If we had only examined baseline plasma levels of cortisol as evidence of stress, we perhaps would not have detected the disruption of the HPA axis of trout in the metal-contaminated waters. Plasma cortisol is a static measure by itself and does not provide information concerning the dynamic nature of the system. Our data suggest either a more rapid turnover of cortisol in the presence of metals or an impaired receptor/secretory mechanism in the adrenocortical cells. It is clearly important not to rely on one measure when assessing the state of the HPA axis in wild animals. Determination of cortisol turnover might be too complicated to perform routinely in the field. However, a simple 24-hr stress test (Norris et al., 1999) or an ACTH-challenge test (Brodeur et al., 1997; Hontela, 1997; Hontela et al., 1995) would provide a better comparison with respect to a reference sample obtained at time of capture. The reference cortisol level could be influenced by the stress of capture and, therefore, may not be the baseline or resting level. However, it would provide a reference point for comparisons within populations and between populations.
The total picture may be even more complicated. We have evidence for disruption of other endocrine-related systems in metal-exposed feral brown trout including reduced liver size, reduced activity of hepatic ornithine decarboxylase activity (Norris et al., 2000) and preliminary unpublished evidence for disturbances in both the immune response system (e.g., altered leucocyte counts and macrophage activity) and in the reproductive system (decreased plasma estradiol levels in females).
Another problem highlighted by our studies is especially important in assessing the actions of EDCs in natural populations. Can short-term laboratory studies be extrapolated to chronic conditions in nature? Perhaps, but our experience with metal exposure suggests we need to test such suspected relationships in the field and not assume anything.
Analyzing impacts of xenobiotics on other hypothalamo-pituitary axes in natural populations poses similar problems for investigators. One major difficulty rests with the establishment of an absolute control condition when in fact the best we may be able to come up with is a reference point or a reference population for comparison. Because of the widespread distribution of many potential EDCs, it may be impossible to find a control population that has not been exposed to the EDC being studied or some other EDC.
We may never be able to prove that xenobiotics have altered the baseline for endocrine functions even though we suspect it to be true. Consider the case for DDT in California amphibians which exhibit measurable body burdens of this pesticide years after its use was banned (see Noriega et al., 1997). Can we use reproductive parameters from such a population as a control for evaluating the actions of DDT or other suspected EDC on the same species in another location? When comparing the alligators of Lake Apopka with those from Lake Woodruff (Guillette et al., 1996), are we actually comparing two points on a dose-response curve to xenobiotics due to the possible pre-exposure of the Lake Woodruff animals to the same or another environmental estrogens (or even non-estrogenic xenobiotics)?
Finally, there are some other additional concerns to be addressed. The possible synergisms of different EDCs on animals in nature generally have not been addressed or adequately assessed even at the level of general chemical classes. When examining potential impacts of a mixture of xenoestrogenic compounds (e.g., alkyphenols, synthetic birth control drugs, estradiol, and other estrogenic compounds found as a mixture in sewage treatment effluents; Mattheisson and Sumpter, 1998; L. Barber, personal communication), is the whole greater than, less than, or equal to the sum of its parts? Similarly, what impact does an EDC-induced change in one axis (e.g., thyroid or adrenal) have on the activity of another axis (e.g., the gonadal axis)?
We need to be concerned about the interpretations of demonstrated or inferred endocrine disruption with respect to a given disturbance. Are statistical differences in an endocrine-disrupted parameter important if they do not translate directly into reduced fecundity or survival of the population at that point in time? The lessons we should have learned about effects of DDT and DES exposures on subsequent generations suggest that we need to be concerned about subtle changes that may be small in themselves but which in combination and/or under different conditions and/or in later generations might reduce the ability of animals to adapt. It may only be in the face of an additional stressor that the magnitude of the present disruption becomes evident.
|
|
ACKNOWLEDGMENTS |
|---|
I wish to thank the following people at the University of Colorado for their contributions to our studies on the brown trout: Edmund Clark, Sean Donahue, Sarah Felt, Earl Larson, Jennifer Lee, Tammy Maldonado, Bradley Micek, James Reed, and Adam Schwindt. Tina Ruth and Robert M. Dores of the University of Denver also provided technical help. The brown trout work was made possible by the cooperation and support of the Colorado Division of Wildlife including Jake Bennett, Steve Brinkman, Barb Horn, Lori Martin, and John Woodling. I also want to thank Dr. Richard E. Jones for his invaluable discussions and both Dr. Jones and Alan Vajda for comments that improved the manuscript. Finally, I want to thank Lou Guillette for both organizing the SICB symposium and allowing me the opportunity to participate.
|
FOOTNOTES |
|---|
1 From the Symposium Endocrine Disrupting Contaminants: From Gene to Ecosystems presented at the Annual Meeting of the Society for Integrative and Comparative Biology, 6–10 January 1999, at Denver, Colorado.
2 E-mail: David.Norris{at}Colorado.edu
|
REFERENCES |
|---|
|
TOP
SYNOPSISINTRODUCTIONTHE NEUROENDOCRINE STRESS...THE STRESS AXIS OF...BROWN TROUT AND METAL...WHERE DO WE GO...REFERENCES |
|---|
Anadu, D.I., G.A. Chapam, L.R. Curtis, and R.A. Tubb. 1989. Effect of zinc exposure on subsequent acute tolerance of heavy metals in rainbow trout. Bull. Environ. Contam. Toxicol, 43:329-336.[Medline]
Banks, J.E., and J.D. Stark. 1998. What is ecotoxicology? An ad-hoc grab bag or an interdisciplinary science?. Integ. Biol, 1:195-204.[CrossRef]
Barton, B.A. 1997. Stress in finfish: Past, present and future—a historical perspective. In G.K. Iwama, A.D. Pickering, J.P. Sumpter, and C.B. Schreck (eds.)Fish stress and health in aquaculture, pp1-33Cambridge University Press, Cambridge.
Barton, B.A., and R.S. Grosh. 1996. Effect of electroshock on blood features in juvenile rainbow trout. J. Fish Biol, 49:1330-1333.[CrossRef]
Barton, B.A., and G.K. Iwama. 1991. Physiological changes in fish from stress in aquaculture with emphasis on the response and effects of corticosteroids. Ann. Rev. Fish Dis, 1:3-26.
Brodeur, J.C., C. Girard, and A. Hontela. 1997. Use of perifusion to assess in vitro the functional integrity of interrenal tissue in teleost fish from polluted sites. Environ. Toxicol. Chem, 16:2171-2178.[CrossRef]
Brown, V., D. Shurben, W. Miller, and M. Crane. 1994. Cadmium toxicity to rainbow trout Oncorhynchus mykiss Walbaum and brown trout Salmo trutta L. over extended exposure periods. Ecotoxicol. Environ. Safety, 29:38-46.[CrossRef][Medline]
Bry, C. 1982. Daily variations in plasma cortisol levels of individual female rainbow trout Salmo gairdneri: Evidence for a post-feeding peak in well-adapted fish. Gen. Comp. Endocrinol, 48:462-468.[Medline]
Bry, C. 1985. Plasma cortisol levels of female rainbow trout (Salmo gairdneri) at the end of the reproductive period: Relationship with oocyte stages. Gen. Comp. Endocrinol, 57:47-52.[CrossRef][Medline]
Chrousos, G.P. 1997. The neuroendocrinology of stress: Its relation to the hormonal milieu, growth, and development. Growth Genet. Horm, 13:1-8.
Colborn, T., D. Dumanoski, and J.P. Myers. 1996. Our stolen future. Penguin Books, USA, Inc., New York.
Davies, P. 1989. Water pollution studies. Investigations on the toxicity of metals to fish. Colorado Division of Wildlife Fed. Aid Study F-33.
Dickhoff, W.W., C.L. Brown, C.V. Sullivan, and H.A. Bern. 1990. Fish and amphibian models for developmental endocrinology. J. Exp. Zool. Suppl, 4:90-97.[Medline]
Fent, K. 1996. Ecotoxicology of organotin compounds. Crit. Rev. Toxicol, 26:1-117.[Medline]
Feyk, L.A., and J.P. Giesy. 1998. Xenobiotic modulation of endocrine function in birds. In R. Kendall, R. Dickerson, J. Geisy, and W. Suk (eds.)Principles and processes for evaluating endocrine disruption in wildlife,. pp121-140SETAC Press, Pensicola, FL.
Foo, J.T.W., and T.J. Lam. 1993. Serum cortisol response to handling stress and the effect of cortisol implantation on testosterone level in the tilapia, Oreochromis mossambicus. Aquaculture, 115:145-158.[CrossRef]
Guillette, L.J., Jr., D.B. Pickford, D.A. Crain, A.A. Rooney, and H.F. Percival. 1996. Reduction in penis size and plasma testosterone concentrations in juvenile alligators living in a contaminated environment. Gen. Comp. Endocrinol, 101:32-42.[CrossRef][ISI][Medline]
Herman, J.P., and W.E. Cullinan. 1997. Neurocircuitry of stress: Central control of the hypothalamo-pituitary-adrenocortical axis. Trends Neuro. Sci, 20:78-84.
Hobson, J.F., and W.J. Birge. 1989. Acclimation-induced changes in toxicity and induction of metallothionein-like proteins in the fathead minnow following sublethal exposure to zinc. Environ. Toxicol. Chem, 8:157-169.
Hontela, A. 1997. Endocrine and physiological responses of fish to xenobiotics: Role of glucocorticosteroid hormones. Revs. Toxicol, 1:159-206.
Hontela, A., P. Dumont, D. Duclos, and R. Fortin. 1995. Endocrine and metabolic disfunction in yellow perch, Perca flavescens, exposed to organic contaminants and heavy metals in the St. Lawrence River. Environ. Toxicol. Chem, 14:725-731.
Keith, L.H. 1997. Environmental endocrine disruptors. A handbook of property data. pp286-300Wiley Interscience, John Wiley and Sons, New York.
Kendall, R., R. Dickerson, J. Geisy, and W. Suk. 1998. Principles and processes for evaluating endocrine disruption in wildlife. SETAC Press, Pensicola, FL.
Kito, H., T. Tazawa, Y. Ose, T. Sato, and T. Ishikawa. 1982. Protection by metallothionein against cadmium toxicity. Comp. Biochem. Physiol, 73:C135-139.[CrossRef]
Levine, S., and H. Ursin. 1991. What is stress?. In M.R. Brown, G.F. Koob, C. Rivier (eds.)Stress: Neurobiology and neuroendocrinology,. pp3-21Marcel Dekker Inc., New York.
Matthiessen, P. 1998. Effects on fish of estrogenic substances in English rivers. In R. Kendall, R. Dickerson, J. Geisy, and W. Suk (eds.)Principles and processes for evaluating endocrine disruption in wildlife, pp239-247SETAC Press, Pensicola, FL.
Matthiessen, P., and J.P. Sumpter. 1998. Effects of estrogenic substances in the aquatic environment. In T. Braunbeck, D.E. Hinton and B. Streit (eds.)Fish ecotoxicology, pp319-335Birkhäuser Verlag, Basel, Switzerland.
McLachlan, J.A., and S.F. Arnold. 1996. Environmental estrogens. Amer. Sci, 84:452-461.
Mounib, M.S., H. Rosenthal, and J.S. Eisan. 1976. Effect of cadmium on developing eggs of the Pacific herring with particular reference to carbon dioxide fixing enzymes. Biol. Reprod, 15:423-428.[Abstract]
Newbold, R.R. 1999. Diethylstilbestrol (DES) and environmental estrogens influence the developing female reproductive system. In R. K. Naz (ed.)Endocrine disruptors, pp39-55CRC Press, Boca Raton, FL.
Noriega, N.C., K.P. Menendez, and T.B. Hayes. 1997. Comparative evaluation of xenoestrogen effects in anurans. Amer. Zool, 37:117A.
Norman, A.W., and G. Litwack. 1998. Hormones, 2nd ed. Academic Press, Inc., San Diego.
Norris, D.O. 1997. Vertebrate endocrinology, 3rd ed. Academic Press, Inc., San Diego.
Norris, D.O., S. Donahue, R.M. Dores, J.K. Lee, T.A. Maldonado, T. Ruth, and J.D. Woodling. 1999. Impaired adrenocortical response to stress by brown trout, Salmo trutta, living in metal-contaminated waters of the Eagle River, Colorado. Gen. Comp. Endocrinol, 113:1-8.[CrossRef][ISI][Medline]
Norris, D.O., S. Felt, J.D. Woodling, and R.M. Dores. 1997. Immunocytochemical and histological differences in the interrenal axis of feral brown trout, Salmo trutta, in metal-contaminated waters. Gen. Comp. Endocrinol, 108:343-351.[Medline]
Norris, D.O., J.M. Camp, T.A. Maldonado, and J.D. Woodling. 2000. Some aspects of hepatic function in feral brown trout, Salmo trutta, living in metal contaminated water. Comp. Biochem. Physiol. C, (In press).
Pascoe, D., and J.H. Beattie. 1979. Resistance to cadmium by pretreated rainbow trout alevins. J. Fish Biol, 14:303-308.
Pickering, A.D., and P. Christie. 1981. Changes in the concentrations of plasma cortisol and thyroxine during sexual maturation of the hatchery-reared brown trout, Salmo trutta L. Gen. Comp. Endocrinol, 44:487-496.[CrossRef][ISI][Medline]
Pickering, A.D., T.G. Pottinger, J. Carragher, and J.P. Sumpter. 1987. The effects of acute and chronic stress on the levels of reproductive hormones in the plasma of mature male brown trout, Salmo trutta. Gen. Comp. Endocrinol, 68:249-259.[CrossRef][ISI][Medline]
Pottinger, T.G., and E. Mosuwe. 1994. The corticosteroidogenic response of brown and rainbow trout alevins and fry to environmental stress during a "critical period.". Gen. Comp. Endocrinol, 95:350-362.[Medline]
Pottinger, T.G., P.H.M. Balm, and A.D. Pickering. 1995. Sexual maturity modifies the responsiveness of the pituitary-interrenal axis to stress in male rainbow trout. Gen. Comp. Endocrinol, 98:311-320.[CrossRef][ISI][Medline]
Pottinger, T.G., T.R. Carrick, S.E. Hughes, and P.H.M. Balm. 1996. Testosterone, 11-ketotestosterone, and estradiol-17ß modify baseline and stress-induced interrenal and corticotropic activity in trout. Gen. Comp. Endocrinol, 104:284-295.[CrossRef][ISI][Medline]
Ross, P., R. Deswart, R. Addison, H. Van Loveren, J. Vos, and A. Osterhaus. 1996. Contaminant-induced immunotoxicity in harbour seals: Wildlife at risk?. Toxicology, 112:157-169.[CrossRef][ISI][Medline]
Schreck, C.B., B.L. Olla, and M.W. Davis. 1997. Behavioral responses to stress. In G.K. Iwama, A.D. Pickering, J.P. Sumpter, and C.B. Schreck (eds.)Fish stress and health in aquaculture, pp145-170Cambridge University Press, Cambridge.
Sheehan, D.M., E. Willingham, D. Gaylor, J.M. Bergeron, and D. Crews. 1999. No threshold dose for estradiol-induced sex reversal of turtle embryos: How little is too much? Environ. Health Perspec, 107:155-159.
Sinley, J.R., J.P. Goettle Jr., and P.H. Davies. 1974. The effects of zinc on rainbow trout (Salmo gairdneri) in hard and soft water. Bull. Environ. Contam. Toxicol, 12:193-201.[Medline]
Sumpter, J.P. 1997. The endocrinology of stress. In G.K. Iwama, A.D. Pickering, J.P. Sumpter, and C.B. Schreck (eds.)Fish stress and health in aquaculture, pp95-118Cambridge University Press, Cambridge.
Swan, S.H., E.P. Elkin, and L. Fenster. 1997. Have sperm densities declined? A reanalysis of global trend data. Environ. Health Persp, 105:1228-1232.[ISI][Medline]
Thomas, P. 1989. Effects of Aroclor 1254 and cadmium on reproductive endocrine function and ovarian growth in Atlantic croaker. Mar. Environ. Res, 28:499-503.[CrossRef]
Thomas, P., and H.W. Wofford. 1993. Effects of cadmium and Aroclor 1254 on lipid peroxidation, glutathione peroxidase activity, and selected antioxidants in Atlantic croaker tissues. Aquat. Toxicol, 27:159-178.[CrossRef]
Tomasso, J.R., K.B. Davis, and N.C. Parker. 1981. aPlasma corticosteroid dynamics in channel catfish, Ictalurus punctatus (Rafinesque), during and after oxygen depletion. J. Fish Biol, 18:519-526.
Tomasso, J.R., K.B. Davis, and B.A. Simco. 1981. bPlasma corticosteroid dynamics in channel catfish (Ictalurus punctatus) exposed to ammonia and nitrite. Can. J. Fish. Aquat. Sci, 38:1106-1112.
Toparri, J., and N.E. Skakkebaek. 2000. Endocrine disruption in male human reproduction. In L. Guillette Jr. and D.A. Crain (eds.)Environmental endocrine disrupters, pp269-290Taylor and Francis, New York.
Wedemeyer, G.A., B.A. Barton, and D.J. McLeay. 1990. Stress and acclimation. In C.B. Schreck and P.B. Moyle (eds.)Methods for fish biology, pp451-489Am. Fish. Soc.
Weiner, H. 1991. Behavioral biology of stress and psychosomatic medicine. In M.R. Brown, G.F. Koob, C. Rivier (eds.)Stress: Neurobiology and neuroendocrinology, pp23-45Marcel Dekker Inc., New York.
Woodling, J.D. 1993. Survival and mortality of brown trout exposed to in-situ acutely toxic concentrations of Cd and Zn. Ph.D. Diss, University of Colorado, Boulder.
Young, M.K. 1994. Mobility of brown trout in south-central Wyoming streams. Can. J. Zool, 72:2078-2083.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||