Comparative endocrinology in the 21st century

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  • 1. GRAND CHALLENGES Comparative endocrinology in the 21st century Robert J. Denver,1*,† Penny M. Hopkins,‡ Stephen D. McCormick,§,ô Catherine R. Propper,k Lynn Riddiford,** Stacia A. Sower†† and John C. Wingfield‡‡ *Department of Molecular, Cellular and Developmental Biology, The University of Michigan, Ann Arbor, MI 48109; † Department of Ecology and Evolutionary Biology, The University of Michigan, Ann Arbor, MI 48109; ‡Department of Zoology, University of Oklahoma, Norman, OK 73019; §Conte Anadromous Fish Research Center, USGS, Turners Falls; ô Department of Biology, University of Massachusetts, Amherst; kDepartment of Biological Sciences, Northern Arizona University, Flagstaff, AZ; **Janelia Farm, Howard Hughes Medical Institute, 19700 Helix Drive, Ashburn VA 20147; †† Center for Molecular and Comparative Endocrinology and Department of Molecular, Cellular and Biomedical Sciences, University of New Hampshire, Durham, NH; ‡‡Section of Neurobiology, Physiology and Behavior University of California at Davis, Davis, CA, USA Synopsis Hormones coordinate developmental, physiological, and behavioral processes within and between all living organ- isms. They orchestrate and shape organogenesis from early in development, regulate the acquisition, assimilation, and utilization of nutrients to support growth and metabolism, control gamete production and sexual behavior, mediate organismal responses to environmental change, and allow for communication of information between organisms. Genes that code for hormones; the enzymes that synthesize, metabolize, and transport hormones; and hormone receptors are important targets for natural selection, and variation in their expression and function is a major driving force for the evolution of morphology and life history. Hormones coordinate physiology and behavior of populations of organisms, and thus play key roles in determining the structure of populations, communities, and ecosystems. The field of endocrinology is concerned with the study of hormones and their actions. This field is rooted in the comparative study of hormones in diverse species, which has provided the foundation for the modern fields of evolutionary, environmental, and biomedical endocrinology. Comparative endocrinologists work at the cutting edge of the life sciences. They identify new hormones, hormone receptors and mechanisms of hormone action applicable to diverse species, including humans; study the impact of habitat destruction, pollution, and climatic change on populations of organisms; establish novel model systems for studying hormones and their functions; and develop new genetic strains and husbandry practices for efficient production of animal protein. While the model system approach has dominated biomedical research in recent years, and has provided extraordinary insight into many basic cellular and molecular processes, this approach is limited to investigating a small minority of organisms. Animals exhibit tremendous diversity in form and function, life-history strategies, and responses to the environment. A major challenge for life scientists in the 21st century is to understand how a changing environment impacts all life on earth. A full understanding of the capabilities of organisms to respond to environmental variation, and the resilience of organisms challenged by environmental changes and extremes, is necessary for understanding the impact of pollution and climatic change on the viability of populations. Comparative endocrinologists have a key role to play in these efforts. 1 E-mail: rdenver@umich.edu Integrative and Comparative Biology, volume 49, number 4, pp. 339–348 doi:10.1093/icb/icp082 Advanced Access publication August 7, 2009 ß The Author 2009. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oxfordjournals.org.
  • 2. 340 Grand Challenges The science of chemical among nerve cells, and hormones and history, and cutting-edge research in neurotransmitters are distinguished the field is now being conducted in mediation from cytokines which function in cell- laboratories throughout the world. Chemical mediators signal between to-cell signaling in defense of the body cells within an organism, or between against invading pathogens. Despite organisms, and function by binding to these operational definitions that dis- Structure and function proteins expressed on the surface of, tinguish among hormones, neurotrans- of animal endocrine or within, target cells to elicit a change mitters, and cytokines, there are many systems—the in cell physiology. They first evolved examples in which a chemical functions contributions of in single-celled organisms for com- in more than one role; i.e. a hormone muniation among individuals (e.g. comparative may also function as a neurotransmit- quorum sensing in bacteria; Miller ter, and vice versa. Furthermore, the endocrinologists to and Bassler, 2001). In metazoans, they endocrine, nervous, and immune biomedical research play pivotal roles in coordinating devel- systems interact at many levels in the In 1849, Arnold Adolph Berthold of opment, physiology, and behavior, maintenance of homeostasis and ¨ the University of Gottingen reported and the interactions among individuals survival. the first endocrinological experiment within populations and communities. The comparative study of hormones in which he castrated cockerels and Chemical mediators influence how in diverse species dates to the early part found that this caused regression of individuals develop, function, and of the 20th century, when the field of secondary sex characters, such as the interact with their environment, but endocrinology first developed. Prior wattles and comb, and the loss they also underlie population-level to 1940, research in endocrinology was of male-typical sexual behavior responses to environmental change. almost exclusively associated with (Berthold, 1849). The term ‘‘hormone’’ Knowledge of these actions is essential medical schools (Kobayashi, 1983). was first coined by Ernest Starling, who to understand and predict how habitat The comparative study of animal together with his brother-in-law, fragmentation, environmental con- hormones developed with the expan- William Bayliss, found that the upper tamination by industrially-derived sion of the field of Zoology during part of the dog’s small intestine, the compounds, and climatic change may the 1940s and 1950s, and the formal duodenum, produced a substance impact the viability of populations, discipline of comparative endo- (secretin) that caused secretion of communities, and ecosystems. crinology was ‘‘born’’ in 1954 with pancreatic juice into the small intestine. The general term ‘‘chemical the First International Symposium on This was the first demonstration that mediator’’, as used here, encompasses Comparative Endocrinology, held at factors transported via the bloodstream several terms that are used within spe- Liverpool, England. Recent decades could act on other tissues and cific scientific disciplines. Hormones, have brought startling advances in our coordinate physiological functions the focus of the science of endocrinol- understanding of animal hormones and (Henderson, 2005). In the 19th century, ogy, are a type of chemical mediators, their actions, in large part due to the role of the pituitary gland in growth originally defined as organic chemicals advances in biochemistry, molecular of the body was suggested by post- that are released from living cells into biology, and genetics. Hundreds of mortem observations of humans that the blood or interstitial fluid and that hormones have now been identified, suffered from acromegaly, but the first travel via the bloodstream some and new medical therapies, means for experimental evidence that the pituitary distance from their site of production enhancing the production of animal produced a substance that influenced to target tissues where they coordinate protein for food, and strategies for bodily functions was the discovery physiological processes (Gorbman and biological control have emerged. The made in the early 20th century that Bern, 1962). As our knowledge of fields of comparative endocrinology pituitary extract caused growth of the hormones and hormone receptors and biomedical endocrinology con- gonads of frogs (Greep, 1988). increases, the definition of a hormone tinue to be closely associated, and The discovery of neurosecretion and continues to evolve. For example, the because hormones play central roles in neuropeptides marked a revolution in classical view of a hormone has changed so many aspects of life, endocrinologists physiology, which led to the integration in recent years to include actions on the will continue to make seminal con- of endocrinology, neurobiology and cell producing the hormone (auto- tributions that impact all disciplines behavior, and later immunology. crine), on adjacent cells within tissues of the life sciences. In this review, we Comparative studies played a pivotal through cell–cell communication discuss some of the major contributions role in the development of the concept (paracrine), or on other individuals of that comparative endocrinologists have of neurosecretion and of the field of the same or a different species (ecto- made to the science of endocrinology, neuroendocrinology. The earliest work crine). Chemical mediators acting as and we highlight the emerging areas of on neurosecretion and neurohemal hormones are often distinguished research and how endocrinologists can structures was carried out in insects from neurotransmitters in that the contribute to the study of organismal (see Kopec, 1922). Ernst and Berta latter are released at synapses to allow biology in the 21st century. Sharrer, and Wolfgang Bargmann, for propagation of electrical signals Comparative endocrinology has a rich working from the 1930s to the 1960s,
  • 3. Grand Challenges 341 are credited with having established the There are many examples of neuro- genes were cloned showed that most intellectual basis for the field of peptides and neuropeptide actions first of the direct-response genes were neuroendocrinology. Ernst Sharrer discovered in nonmammalian species transcription factors (King-Jones and first developed the concept of neuro- that were subsequently found to play Thummel, 2005). Recent studies with secretion based on his work with the important roles in human physiology insect, crustacean, and amphibian minnow, Phoxinus laevis, in which he and disease states. For example, the nuclear hormone receptors are helping postulated that specific neurons in the neuropeptide arginine vasotocin (the to unravel the complexities of receptor preoptic nucleus of the hypothalamus mammalian homolog is arginine dimerization (Kozlova et al. 2009), possessed endocrine activity related to vasopressin–AVP) was first found to transcriptional regulation (King-Jones pituitary function (Klavdieva, 1995). influence reproductive behavior in and Thummel, 2005; Buchholz et al. He and his wife Berta conducted amphibians, and is now known to con- 2006; Hopkins et al. 2008), and the comparative studies on animal neuro- trol social behavior in diverse vertebrate roles of nuclear hormone receptors in secretory systems, dividing their efforts, species (Goodson and Bass, 2001). animal development (King-Jones and with Berta studying invertebrates Recent discoveries implicate AVP in Thummel, 2005; Buchholz et al. 2006). (Scharrer, 1941) and Ernst studying human pair-bonding behavior In addition to the well-known vertebrates (Scharrer and Scharrer, (Walum et al. 2008), and mental genomic actions of steroid hormones, 1937). Wolfgang Bargmann is credited health disorders such as autism rapid, nongenomic actions are now with having firmly established the (Wassink et al. 2004; Egashira et al. known to be mediated by the receptors existence and functional role of neuro- 2007). The isolation of urotensin located in the plasma membrane. Rapid secretion in vertebrates (Klavdieva, peptides from the fish caudal neuro- actions of steroids were first discovered 1995). Bebnado Houssay, working secretory system (the urophysis) is in the 1970s by Godeau et al. (1978) with toads, was the first to show that another example of how comparative who showed rapid, membrane- blood flowed from the hypothalamus endocrinology has laid the foundation mediated effects of progesterone on to the pituitary gland (Houssay et al. for understanding human physiology. frog oocyte maturation. The first 1935a, 1935b), and Geoffrey Harris The recently discovered human discovery and pharmacological charac- later showed, in studies conducted homolog of fish urotensin II is now terization of a membrane steroid recep- with rats, that the functioning of the implicated in human cardiovascular tor located in neuronal membranes was nervous and the endocrine systems function and heart disease, and may carried out in the male rough-skinned were linked through neurohormones also function as a neurotransmitter/ newt in which the stress hormone produced in the hypothalamus that neuromodulator in the brain (Maguire corticosterone causes rapid inhibition controlled pituitary hormone secretion and Davenport, 2002). of males’ clasping behavior (Orchinik (Harris and Jacobsohn, 1952). The nuclear mechanisms of action of et al. 1991). In 2003 Peter Thomas and The contribution of comparative steroid hormones were first discovered colleagues, working with ovaries of the studies to the field of neuroendocri- by comparative biologists working spotted sea trout, isolated and charac- nology continues today. Many new with insects, and these and other non- terized the first G protein-coupled neuropeptides were originally discov- mammalian model species continue receptor (GPR) that mediates rapid ered in invertebrates and nonmamma- to play a central role in the study of steroid actions. The fish receptor was lian vertebrates, and their orthologs steroid hormone action in develop- activated by progestins (Zhu et al. were subsequently found in mammals. ment, physiology, and disease. Steroid 2003b), and subsequently orthologous For example, a cardioexcitatory peptide hormones bind to nuclear receptors to genes were identified in mice and with a characterisitic FMRFamide regulate gene expression. This concept humans (Zhu et al. 2003a). These find- C-terminal sequence was first isolated first came from studies of the insect ings have set the stage for the discovery in 1977 by Price and Greenberg from steroid ecdysone that was found to of other GPR steroid receptors, and the the ganglia of the clam, Macrocallista induce ‘‘puffing’’ of the giant polytene expansion of the field of nongenomic nimbosa (Price and Greenberg, 1977). chromosomes in the salivary glands of steroid hormone actions. Recently, RFamide peptides were midges and flies. This phenomenon was The invertebrates have played discovered in mammals and found to first observed by Clever and Karlson a major role in the development of the play critical roles in controlling pituit- (1960) in the midge Chironomus field of comparative endocrinology, ary hormone secretion, reproduction, and later expanded into a theory of and the findings of invertebrate appetite and pain, among other func- a transcriptional cascade of hormone endocrinologists have had far-reaching tions (Chartrel et al. 2003; Fukusumi action by Ashburner et al. (1974). This impact on the life sciences as a whole. et al. 2006; Tsutsui, 2009). The theory, which has had broad impact For example, studies by Michael concentration of neuropeptides in the in biology and medicine, described Berridge in the 1970s on the blowfly frog brain is estimated to be an order a gene-regulation cascade directly led to the discovery of the phosphatidy- of magnitude greater than that of induced by the hormone ecdysone and linositol signaling pathway, its role mammalian brain, which has facilitated that led to the tissue-specific activation in mobilization of intracellular the discovery of novel vertebrate neuro- or suppression of genes. Work done in calcium, and more generally the role peptides (Chartrel et al. 2006). the early 1990s in which ecdysone target of calcium in intracellular signaling
  • 4. 342 Grand Challenges (Berridge, 1993). The role of neuro- are critical for population sustainability mediate trade-offs among life-history peptides acting on the central nervous in the wild. The comparative study of traits (e.g. development versus growth; system to elicit discrete behaviors was animal endocrine systems can lead to growth versus reproduction), the inter- first discovered in the mollusk, Aplysia the development of new model systems actions between the environment and californica, in which egg-laying for biomedical research, and can genes, and the establishment of con- hormone was shown to act on the provide a rational basis for the develop- straints on phenotypic expression (the nervous system to elicit stereotypical ment of strategies for wildlife range and limits of phenotypic plasti- oviposition behavior (Strumwasser, conservation. city) and phenotypic evolution (e.g. 1984; Smock and Arch, 1986). maximum, species-specific body size Another well-characterized example of Evolutionary or allometric relationships among hormonal control of behavior is ecdysis endocrinology organs/body structures). Hormones in insects, in which ecdysis-triggering also play a key roles in the evolution Variation in Darwinian fitness results hormone and eclosion hormone of development (e.g. heterochrony from variation in organismal form, cooperate to activate neuropeptidergic developmental plasticity, polyphen- function and life-history traits. pathways in the nervous system leading isms) and the evolution of life histories Hormones have widespread and diverse to ecdysis (Truman, 2005; Zitnan et al. (e.g. timing of metamorphosis or actions in coordinating the expression 2007). More recently, studies of insects birth, survivorship, age at first repro- of animal form and function, and are are leading the way in linking control of duction, clutch or litter size, and thus key players in determining fitness. growth and body size, and its hormonal frequency of reproductive cycles) Natural selection acts on genes that regulation, to nutrient intake and (Zera et al. 2007). code for hormones, hormone synthe- insulin signaling (Nijhout, 2003a, Variation in endocrine function sizing or metabolizing enzymes, 2003b; Mirth and Riddiford, 2007; underlies variation in animal morpho- hormone binding proteins and recep- Shingleton et al. 2007). tors, and hormone signaling pathways logies and life-history patterns. For The study of mammalian model that influence the evolution of animal example, components of thyroid organisms such as the rat and the diversity. Evolutionary endocrinology physiology determine variation in mouse have provided extraordinary is a subdiscipline of evolutionary metamorphic timing among frog insight into the molecular and cellular physiology (Garland and Carter, species, and this timing correlates with mechanisms of hormone biosynthesis 1994), whose broad goal is to under- the relative permanence of the larval and action, but relying on one or a stand the manner and mechanism by habitat (Buchholz and Hayes, 2005). few species for research has important which organismal function has Thus, evolution of the length of the limitations. The model systems responded to natural selection (Zera larval period, which is a central approach assumes that the findings et al. 2007). Specifically, it is the study amphibian life-history trait, is governed from a handful of model organisms of how animal hormones and their by changes in the endocrine system that (now primarily the mouse) can be signaling pathways have evolved to controls metamorphosis. The evolution extrapolated broadly to other species, control diverse developmental, physio- of paedomorphic life histories among most importantly to humans. logical, and behavioral processes; of salamander species likely depended, However, these animal models may evolutionary relationships among in part, on mutations in genes that con- not be ideal for some basic research animal species by comparing endocrine trol production or action of thyroid questions such as the roles of hormones organs, processes and genes; and of hormone (Voss et al. 2000; Voss et al. in development, for which invertebrate how hormone systems underlie adapta- 2003; Safi et al. 2006). Size-dependent, or nonmammalian vertebrate models tion to diverse environments and the photoperiodic stimulation of growth may be better suited. Importantly, evolution of new traits and formation hormone and cortisol both control model systems cannot represent the of new species. development of salinity tolerance that diversity of structure and function, Hormones influence virtually every occurs during downstream migration and life-history strategy among morphological, physiological, and of juvenile salmon, and this endocrine animals. This is of particular concern life-history trait of an animal. Under- response is reduced in landlocked for conservation biology, in which standing the physiological/endocrino- salmon that have abandoned seaward species use different physiological and logical mechanisms is essential to our migration. (McCormick, 2009). These behavioral strategies to survive, and understanding of the mechanistic examples show how the study of may show differential susceptibility to underpinnings for evolutionary corre- hormone-dependent phenomena in a environmental contaminants and to lations and constraints commonly developmental and ecological context environmental degradation (environ- observed at higher levels of biological can contribute to an understanding of mental stressors). The study of one or organization (e.g. animal form and the mechanistic basis for the evolution a few model species may not provide physiological performance) (Husak of animal diversity, and provide an relevant information for the species et al. 2009). The actions of hormones intellectual basis for the development of concern, and inbreeding of model represent a complex network of inter- of a subfield of comparative endo- species in the laboratory reduces inter- actions, and selection may act at any crinology, evolutionary developmental individual variation and plasticity that point within these networks. Hormones endocrinology.
  • 5. Grand Challenges 343 Variation in nucleotide sequence in shifts in sex-typical behavior in reef fish associations, and the evolution of hormone and hormone-receptor genes that change sex (Semsar and Godwin, diversity in physiological control. are linked to developmental, physiolo- 2003), and in behavioral diversification The nuclear receptor superfamily gical, morphological, and behavioral in pupfishes found in Death Valley evolved over 500 million years ago, diversity among species. For example, (Lema, 2006, 2008). The neural/ and represents a fascinating case study changes in the melanocortin receptor neuroendocrine pathways in which of molecular evolution. Joe Thornton type 1 (MC1R) gene, which mediates AVT functions as a neurotransmitter, and colleagues used phylogenetic actions of hormones, such as -MSH, and that mediate sex-typical behaviors, reconstruction to ‘‘resurrect’’ the on pigmentation, are linked to vari- show plasticity in response to a chan- predicted ancestral steroid receptors, ation in melanin-based, dark plumage ging social environment (Semsar and and then they tested the functional color in birds (Mundy, 2005; Pointer Godwin, 2003; Lema, 2006, 2008). characteristics of these receptors using and Mundy, 2008), and in coat color Steroid hormones play central roles in techniques of modern molecular endo- in mammals (Nachman et al. 2003). sexual and stress-related behaviors, and crinology. This allowed the discovery Changes in the coding sequence of the modulation of their production and that the ancestral steroid receptor of MC1R underlie the evolution of actions plays a key role in behavioral vertebrates was an estrogen receptor- pigmentation loss in cave-dwelling fish plasticity and in the evolution of like protein that first evolved in (Gross et al. 2009). Interestingly, the behavioral modes and social structures invertebrates (Thornton, 2001; de-pigmented phenotype has arisen (Adkins-Regan, 2005). Neurohor- Thornton et al. 2003). independently in geographically sep- mones of the corticotropin-releasing arate caves through different mutations hormone family mediate environmen- Environmental of the MC1R. Genes like the MC1R, and tal effects on the timing of amphibian other hormone or hormone-receptor metamorphosis and on the timing of endocrinology, global genes, may be frequent targets for birth in mammals (Denver, 2009). change, and conservation mutation in the repeated evolution of These are just a few examples of the One of the greatest challenges to bio- similar phenotypes, owing to the cen- many ways in which hormones mediate logists in the 21st century is to under- tral roles they play in development, environmental effects on development, stand the molecular and cellular physiology, and morphology. Insulin- physiology, and behavior and provide mechanisms underlying how organisms like growth factor 1 (IGF-1) plays a the mechanistic basis for the evolution perceive environmental change, and key role in controlling body growth, of diversity in morphology and life then transduce that information into and variation in the IGF-1 gene is history. neural and neuroendocrine secretions linked to variation in body size in The application of molecular biology that orchestrate morphological, phy- dogs, suggesting that this locus is to the function and evolution of the siological, and behavioral responses. a target for both artificial and natural endocrine system has revolutionized The bewildering array of potential selection (Sutter et al. 2007). The scal- comparative and evolutionary endocri- cues from the physical and social envir- ing of body parts (allometric scaling) is nology. The mapping of genomes from onments can actually be simplified a fundamental feature of animal form species in key phylogenetic positions, into two major groups (or types). and function, and findings in insects such as the cephalochordate amphioxus First, environmental information can point to a key role for insulin/IGF (Branchiostoma floridae), the urochord- be used for the predictable environment signaling in controlling allometric rela- ate sea squirt (Ciona intestinalis), such as day and night, high tide/ tionships among body parts (i.e. body and the vertebrate sea lamprey low tide, and the seasons. Therefore, shape; Emlen et al. 2006; Shingleton (Petromyzon marinus), is allowing organisms can use environmental cues et al. 2007). Recent work in inverte- comparative endocrinologists to under- to time and prepare for future events brates and vertebrates implicate stand the evolutionary history of such as breeding, migration and hiber- insulin/IGF signaling in the control vertebrate endocrine systems at the nation. Hormones thus transduce and evolution of lifespan (Partridge, molecular level (Sherwood et al. 2005; predictive environmental signals, such 2008). Holland et al. 2008; Kavanaugh et al. as annual change in day length Hormones are key mediators of 2008; Paris et al. 2008; Sower et al. (or photoperiod), temperature, rainfall, phenotypic plasticity (the property of 2009; Tello and Sherwood, 2009). or abundance of food into develop- individual genotypes to produce Molecular phylogenetic analyses of the mental, morphological, physiological, different phenotypes under different neurohypophysial nonpeptides (Acher and behavioral responses. While environmental conditions) (Pigliucci, et al. 1997), gonadotropin-releasing mechanisms underlying photoperiodic 2001). Phenotypic plasticity may be hormone (Kavanaugh et al. 2008; responses have received extensive an important driver of evolutionary Okubo and Nagahama, 2008; Tsai attention, mechanisms whereby organ- change (e.g. through genetic assimila- and Zhang, 2008; Sower et al. 2009), isms respond to other predictive tion) (Pigliucci et al. 2006), and may and proopiomelanocortin (Dores environmental cues remain much less influence the evolution of animal life and Lecaude, 2005), to name just a studied. histories. For example, the neurohor- few, have helped to clarify phylogen- Second, organisms must respond mone arginine vasotocin (AVT) causes etic relationships, structure/function appropriately to unpredictable events
  • 6. 344 Grand Challenges in the environment, including potential 1996; Guillette and Guillette, 1996; are altered by EDCs, much more infor- stressors such as storms, predators, Taylor et al. 2005; Hogan et al. 2008; mation is needed concerning the effects drought, and floods. In recent decades, Iguchi and Katsu, 2008). Some of of endocrine disrupting chemicals on human disturbance (loss of habitat, the earliest indications that chemicals free-living populations in which subtle urbanization, pollution, recreational in the environment could mimic effects on development, physiology and disturbance, invasive species, and endogenous hormones came from behavior may have far reaching, long- spread of disease) has exacerbated how studies of invertebrates in the 1960s term effects not necessarily apparent animals cope with the unpredictable and 1970s that showed that chemicals from studies of captive animals. Basic environment (e.g. Travis, 2003). derived from newspaper could mimic knowledge of how animals perceive In contrast to hormonal responses insect juvenile hormone (Slama and and transduce environmental infor- to the predictable life cycle, animals Williams, 1966) and that water-borne mation will thus be fundamental to must respond to unpredictable events chemicals could disrupt crustacean life understanding how, and whether, they during, or very soon after, the perturba- cycles (Bookhout and Costlow, 1970). can cope with EDCs (Wingfield and tion. This is a fundamentally different The study by Slama and Williams Mukai, 2009). suite of mechanisms from responses (1966) led to the development of to the predictable. Thus, although Insect Growth Regulators (hormonal hormones mediate the interaction mimics) for the selective control of Conservation endocrinology between the environment and the insect pests (Dhadialla et al. 1998). genotype, the mechanisms involved In the 1980s, several investigators dis- Endocrinologists can make significant can be very different depending covered that tributyltin from marine contributions to conservation biology upon context and predictability. paints acts as a hormonal mimic that by helping to understand the mechan- Understanding these two major types induces intersexes (imposexes) in isms by which organisms cope with of response to the environment, and mollusks (Spence et al. 1990; Alzieu, changing environments. In recent interactions between them, is crucial 1998). Numerous studies of vertebrate years physiologists and endocrino- for an understanding of how, and wildlife and experimental animals logists have provided approaches to whether, organisms will cope with have since shown that EDCs can address conservation issues relevant to global change (Wingfield, 2008). have estrogenic, anti-androgenic, and land managers who make decisions anti-thyroid effects (Diamanti- on how to conserve habitat as well as Endocrine disruption Kandarakis et al. 2009). In 2008, protect specific populations (e.g. the United States Environmental Cockrem, 2005; Wikelski and Cooke, Disruption of hormone signaling by Protection Agency (EPA) established 2006). For example, a given population industrially derived chemicals [endo- crine disrupter compounds (EDCs)] an Endocrine Disrupter Screening may be impacted by environmental may compromise organismal function, Program comprised of a battery of stress, which can often be detected by and is now recognized as a significant tests to evaluate the potential for measuring a number of endocrine- threat to the health of human and wild- industrially derived chemicals to alter related endpoints (Cyr and Romero, life populations. A recent position androgen, estrogen, or thyroid- 2009). Endocrine biomarkers may also paper published by the Endocrine hormone signaling (US EPA, 2008). be useful in detecting EDCs and other Society highlights the growing evidence Several of the assays use nonmamma- lethal and sublethal contaminants. and concern for EDC impacts on lian species (e.g. the amphibian meta- Alternatively, changes in the environ- humans and wildlife (Diamanti- morphosis assay; the fish reproduction ment such as climate change may lead Kandarakis et al. 2009). The potential assay) for which knowledge of the to inappropriate timing of endocrine- for endocrine disruption was first biology and endocrinology of these ani- controlled life history events, the recognized when wildlife populations mals was derived from basic research phenology of which can be determined began to experience reproductive conducted by comparative endocrinol- by examining altered patterns of circu- problems; e.g. decline of the bald eagle ogists, and upon which future develop- lating hormones. Field endocrine population on the Gulf Coast of Florida ment of these and other assays will techniques can provide substantial in the late 1940s, of the river-otter depend. information on the growth, stress and population in England in the 1950s, While some populations, or individ- reproductive status of individual ani- of the herring-gull population of Lake uals within populations appear to be mals, thereby providing insight into Ontario, of the western-gull population unaffected by EDCs, others may be current and future responses of popula- of the Channel Islands of California much more sensitive and show tions to changes in the environment. in the 1970s, and population decline increased mortality or reduced repro- In addition, basic information on and male reproductive deformities in ductive success (e.g. Norris, 2000; the environmental requirements of alligators living in Lake Apopka, Norris, 2006). What are the mechan- individual species for normal growth Florida, in the 1980s, as well as limb isms for these differences? In addition and development will provide critical deformities and altered sex ratios of to a need for knowledge of the mole- information for species and ecosystem frogs in the 1990s (Colburn et al. cular and physiological pathways that conservation.
  • 7. Grand Challenges 345 Comparative eventual acceptability of these treat- include: By what sensory modalities ments. Research by comparative do organisms perceive environ- endocrinology and food endocrinologists can contribute in mental change? How is this sensory in the 21st century a substantive way to providing infor- information transduced into neuro- Hormones are critical control elements mation and the clarity necessary for endocrine and endocrine secretions of growth and reproduction and have decisions on these trade-offs. (stimulatory and inhibitory)? In what long been targeted to increase animal Domestication of new species, ways will global change (climate and food production. Knowledge of the especially in aquaculture, can bring human disturbance) affect organisms endocrine control of growth, fat protein production to areas with other- in relation to their ‘‘perception/ content, and appetitive behavior has wise limited production capacity and transduction systems?’’ For example, led to improvements in husbandry reduce pressure to harvest natural an organism whose life cycle is driven methods in many species. Sex steroids populations. Knowledge of the basic by photoperiod may become mis- are used to increase protein and to environmental requirements for the matched with other changes in its decrease fat content in most of the proper endocrine control of growth environment (e.g., global warming); beef production in the USA (Raloff, and reproduction will be critical for whereas, other organisms that respond 2002). Since 1994, growth hormone rearing of these newly domesticated to multiple environmental signals has been approved and widely used in species and for improving traditional such as temperature and photoperiod the USA to improve milk yield in cattle. approaches to husbandry of established will be more likely to adjust. What is Gonadotropin releasing hormone is species. Innovative techniques in the potential for new and existing widely used to induce mating and animal husbandry, such as the use chemicals to affect neuroendocrine sys- spawning in many cultured fish species, of altered photoperiod to improve tems? Why are some individuals or spe- especially when initial domestication is animal growth or the timing or cies less susceptible to the impacts of occurring (Mylonas and Zohar, 2000). reproduction, are often determined or exposure to EDCs while others are Growth hormone-transgenic salmon enlightened by previous understanding greatly affected? Can we develop sensi- have increased growth rates and con- of basic endocrinology (Bjornsson, tive, high-throughput assays for EDCs version efficiency (Devlin et al. 2000). 1997). Hormones and receptors can that will be representative of endocrine Thus, there is an opportunity for use of act as endpoints for selection of disruption in a broad range of species? hormone supplements and transgenic desirable traits (Oksbjerg et al. 2004). Only comparative studies of diverse animals to increase the efficiency, There is increasing interest in species will allow us to address such total productivity and profitability of understanding and promoting animal questions. farming operations. welfare in farming, and endocrinology Comparative endocrinologists have There are also potential negative can contribute by determining the important roles to play in many areas effects of these approaches. Hormone factors that impose stress or com- of the life sciences, such as the develop- treatments can alter the composition promise the health of domesticated ment of alternative animal model sys- of food destined for human consump- animals. tems for discovery of novel hormones tion, such as the IGF-I content of and hormone-signaling pathways; the milk or steroid content of meat, with Frontiers in comparative discovery of new pharmaceuticals possible impacts on human health. endocrinology to treat human disease; the design of Animals themselves may be negatively The scope of comparative endocrin- hormonally-based strategies for pest influenced by hormone treatments; ology has expanded dramatically since control; the development of sensitive, growth hormone treatment of cattle its formal origins over 50 years ago. representative and high-throughput has been shown to result in increased Studies of hormones and their actions endocrine-screening assays for EDCs; mastitis, infertility, and lameness impact virtually every field of the life the analysis of the impact of global (Dohoo et al. 2003). Broader environ- sciences, and the importance of work climatic change on animal populations; mental impacts are also of concern. by comparative endocrinologists for the elucidation of pathways and Natural and synthetic hormones may the study of organismal biology in the mechanisms of evolution through the be released into the soils and waterways 21st century will only continue to study of endocrine genes and struc- from concentrated animal-feeding increase. The neuroendocrine system tures; and the development of more operations (CAFOs) with potential transduces environmental signals into efficient means for the production of impact on animal and human health developmental, physiological, and animal protein to feed the world’s (Jensen et al. 2006). Inadvertent release behavioral responses, and knowledge growing human population. This is of transgenic animals could result in of these mechanisms is essential for not intended to be a comprehensive their interaction, including breeding, understanding how organisms interact list, or to limit research in this field, with wild animals (Muir and Howard, with their environment and how the but rather to serve as a stimulus for 2002). Both the reality and perception environment influences organismal further thought and discussion. of these impacts has the capacity to form, function, and survival. Some Critical to these efforts is the recruit- influence consumers’ responses and important unanswered questions ment and broad training of young
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