The hypothalamus–pituitary–thyroid axis in teleosts and amphibians: Endocrine disruption and its consequences to natural populations

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Abstract

Teleosts and pond-breeding amphibians may be exposed to a wide variety of anthropogenic, waterborne contaminants that affect the hypothalamus–pituitary–thyroid (HPT) axis. Because thyroid hormone is required for their normal development and reproduction, the potential impact of HPT-disrupting contaminants on natural teleost and amphibian populations raises special concern. There is laboratory evidence indicating that persistent organic pollutants, heavy metals, pharmaceutical and personal care products, agricultural chemicals, and aerospace products may alter HPT activity, development, and reproduction in teleosts and amphibians. However, at present there is no evidence to clearly link contaminant-induced HPT alterations to impairments in teleost or amphibian population health in the field. Also, with the exception of perchlorate for which laboratory studies have shown a direct link between HPT disruption and adverse impacts on development and reproductive physiology, little is known about if or how other HPT-disrupting contaminants affect organismal performance. Future field studies should focus on establishing temporal associations between the presence of HPT-disrupting chemicals, the occurrence of HPT alterations, and adverse effects on development and reproduction in natural populations; as well as determining how complex mixtures of HPT contaminants affect organismal and population health.

Introduction

Accumulating evidence over the last two decades indicates that a wide range of anthropogenic chemicals have the ability to alter endocrine function in humans and wildlife. While most attention has focused on endocrine-disrupting chemicals (EDCs) that affect the hypothalamus–pituitary–gonadal axis and reproductive functions in humans and wildlife, numerous laboratory and field studies suggest that many EDCs can also target the hypothalamus–pituitary–thyroid (HPT) axis. EDCs that impact the HPT are of particular concern to teleosts and pond-breeding amphibians as these animals may be exposed to waterborne contaminants during a portion or the entirety of their life span, thus representing a worst case exposure scenario. Furthermore, because the HPT axis in teleosts and amphibians is required for normal development and metamorphosis, their larvae are exquisitely sensitive to disruption of HPT function. Additionally, current knowledge suggests that the regulation of, and contaminant impacts on, the HPT axis are founded on similar mechanisms in these two vertebrate taxa. Thus, unlike previous reviews of the subject of HPT disruption, and based on the premise that broader perspectives may yield useful insights, the present review deals with thyroid endocrine disruption in teleost fishes and amphibians collectively.

Teleosts and amphibians may inhabit surface waters containing complex mixtures of EDCs that can have subtle affects on thyroid function with little or no outward signs of toxicity at the time of exposure. Thus, establishing causal links between HPT axis disruption and reduced fitness and reproductive success in natural fish and amphibian populations can be challenging. In 2002, the World Health Organization (Damstra et al., 2002) published a framework for assessing whether EDCs cause adverse effects in humans and wildlife. The WHO framework is clearly recognizable as the basic tenets of Koch and Loeffler’s postulates (Loeffler, 1884) as modified from more recent epidemiological literature on the establishment of causal links between the environment and disease (Damstra et al., 2002). Based upon this framework, the criteria for establishing causal links between EDCs and thyroid disruption would include,

  • demonstrating a temporal relationship between exposure to the contaminant and changes in HPT endpoints;

  • demonstrating a strong association between exposure to the contaminant and effects on the HPT axis;

  • demonstrating a consistent HPT response across multiple studies;

  • determining the biological plausibility of the response;

  • determining whether recovery of the HPT axis occurs following removal of the contaminant.

While laboratory studies have shown effects of various EDCs on the HPT axis and on thyroid-dependent development and physiology in teleosts and amphibians, much less attention has been directed at studying thyroid disruption in natural populations. However, the results of a number of field studies suggest that exposure to waterborne contaminants can disrupt the HPT axis in these organisms and, consequently, perhaps also their population health. The purpose of this manuscript is to review the evidence that EDCs can impact HPT function in natural fish and amphibian populations. To understand the relevance of HPT disruption in natural populations, we first provide brief descriptions of the function and regulation of the HPT axis, its role in development and reproduction, and the typical endpoints of HPT activity used in EDC studies.

The use of trade, product, industry or firm names or products is for informative purposes only and does not constitute an endorsement by the U.S. Government or the U.S. Geological Survey.

Section snippets

The HPT axis

Unlike amphibians, most teleost fishes do not have an organized pair of thyroid glands. Their thyroid follicles are found dispersed among the afferent branchial arterioles of the ventral region of the pharynx, individually or in clusters. However, the basic structure and function of the thyroid follicle is fairly conserved across vertebrates (Paris and Laudet, 2008). A thyroid follicle consists of epithelial cells that are surrounded (supported) by a basement membrane and encloses a lumen.

Role of thyroid hormone in development and reproduction

For many years, the notion that TH is important for teleost and amphibian embryogenesis was based primarily on knowledge that the hormone is maternally inherited in eggs and thus present well before its endogenous production, and that embryos contain the necessary mechanisms to regulate the availability and activity of TH (i.e., deiodinases and TRs) (Weber et al., 1992, Weber et al., 1994, Nowell et al., 2001, Morvan Dubois et al., 2006, Tindall et al., 2007, Walpita et al., 2007). Experimental

Central effects-thyroid histopathology

Levels of hypothalamic regulatory hormones and TSH would be ideal endpoints to measure in studies of HPT responses to potential thyroid-disrupting agents. However, there are several technical drawbacks that make these endpoints difficult to determine. First, TRH or CRF are released locally from nerve terminals innervating the pituitary gland (teleost fishes) or median eminence (amphibians), and thus their levels in the peripheral circulation are very low. Also, because of species differences in

Thyroid function in teleosts and amphibians inhabiting surface water contaminated with persistent organic pollutants and heavy metals

Persistent organic pollutants (POPs) are anthropogenic contaminants that do not quickly degrade in the environment, are highly lipophilic, and accumulate to a significant extent in fatty tissues. Because of their high lipid solubility, POPs have a tendency to bioaccumulate in the food chain. POPs include such well-known contaminants as DDT (1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane) and its metabolites, polychlorinated biphenyls (PCBs), and polycyclic aromatic hydrocarbons (PAHs). While

Thyroid function in teleosts and amphibians inhabiting surface water contaminated with the military and aerospace waste product perchlorate

Perchlorate is an anion containing one chloride atom and four oxygen atoms that, because of its high oxygen content, is widely used an oxidizer in liquid-fueled rockets, airbags, and pyrotechnics. Perchlorate contamination of surface and ground water occurs from military, aerospace and other commercial sources (Mayer et al., 2006), but perchlorate also occurs naturally in arid places on the surface of the earth (Dasgupta et al., 2005, Furdui and Tomassini, 2010, Kounaves et al., 2010) as a

Response of teleosts and amphibians to contamination from wastewater/effluent

Municipal wastewater contains several types of chemicals that may act as potential thyroid-disrupting contaminants (Kolpin et al., 2002, Barnes et al., 2008, Focazio et al., 2008) including nonylphenol (NP), a nonionic detergent metabolite (surfactant); triclosan, a fungicide; polybrominated diphenylethers, or PBDEs, which are used as flame retardants; bisphenol A (BPA), a plasticizer; and ethynylestradiol (EE2), a synthetic estrogen used in birth control pills.

Nonylphenol has been shown in

Impact of agricultural land use on thyroid function

Agricultural chemicals may enter surface waters through runoff, atmospheric deposition or through contamination of groundwater. Individual pesticides reported to alter thyroid function in teleosts and amphibians under laboratory conditions include acetochlor (Cheek et al., 1999, Crump et al., 2002, Helbing et al., 2006, Li et al., 2009), atrazine (Larson et al., 1998), endosulfan (Sinha et al., 1991, Park et al., 2004, Coimbra et al., 2005), malathion (Yadav and Singh, 1987, Sinha et al., 1992

Summary and conclusions

Despite the considerable and growing body of knowledge gained from laboratory studies, relatively little information is available concerning disruption of the HPT axis in the field and its consequences to natural teleost and amphibian populations. Although the results of several studies (Table 1) indicate that HPT disruption does in fact occur in contaminated aquatic habitats, additional studies are needed to determine the link between HTP disruption in the field and relevant indices of

Acknowledgments

The Texas Cooperative Fish and Wildlife Research Unit is jointly supported by Texas Tech University, Texas Parks and Wildlife Department, U.S. Geological Survey, Wildlife Management Institute, and U.S. Fish and Wildlife Service. We thank Drs. Nathan Collie, Sandeep Mukhi, Phil Smith, Ernest Smith, and Christopher Theodorakis for reading earlier drafts of this manuscript.

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