Variation in thyroid hormone physiology in natural animal populations
1. Introduction
Hormones are important mediators in the responses of a suite of phenotypic traits to environmental changes. Therefore, populations inhabiting different environments are expected to vary in several hormonal pathways. Such variation results from both plastic response to environments and genetic differences. Therefore, information about the genetic basis of hormonal variation is crucial to better understand the ecological and evolutionary mechanisms of phenotypic diversification in animals. Furthermore, information about the racial and geographical variation in hormone physiology is crucial for better diagnosis of hormone-related diseases in clinical fields. Thyroid hormones play key roles in regulation of many physiological and behavioral traits, such as metabolism, ion homeostasis, basal activity, and longevity. Therefore, thyroid hormone can play important roles in adaptation to external environments. In the present study, we review interspecies, racial, geographical, and interindividual variation in the thyroid hormone pathways in humans and other animals. The present review focuses on natural and subclinical variation in thyroid hormone physiology and will not cover the genetic basis for congenital hypothyroidism [1,2,3,4,5], congenital hyperthyroidism [6,7], autoimmune diseases [8], and thyroid cancers [9], for which a number of good review articles are already available. We also review what is known about the genetic basis for such variation. We found several shared features in the patterns of variation in thyroid hormone physiology in humans and other animals. This review demonstrates the importance of undertaking further integrative studies of human genetics and animal ecology for a better understanding of the ecological and genetic mechanisms of variation in thyroid hormone signaling pathways.
2. Variation in thyroid hormone physiology in humans
2.1. Interindividual, geographical, and racial variation
Geographical variation in the frequency of euthyroid endemic goiter has been extensively investigated [10,11,12]. In addition to iodine deficiency, other factors, such as smoking, age, sex, goitrogens, and body mass index, can also influence the etiology of euthyroid endemic goiter [13]. Although genetic predisposition to euthyroid goiter has been demonstrated [12,13,14], the molecular genetic mechanisms underlying the variation in susceptibility to goiter are not well understood. Polymorphism at the thyroglobulin (
Racial variation in the level of thyroid-stimulating hormone (TSH), one of the major hormones regulating synthesis and secretion of thyroid hormone, has been also found. Multiple studies have revealed that serum TSH levels are higher in whites and Mexican Americans than in blacks [20,21,22]. These results suggest that race-specific reference values of TSH are necessary for evaluation of thyroid hormone-related diseases. Currently, the genetic and ecological basis for the racial variation in TSH levels is not well understood. The serum levels of thyroxine-binding globulin (TBG), a major thyroid hormone-binding protein in plasma, are lower in Australian Aborigines than in Caucasians in Western Australia [23]. Aborigines have a TBG variant that has reduced affinity for thyroid hormone and is more susceptible to heat and acid denaturation [24,25,26]. Two amino acids are substituted in this variant, one of which is considered responsible for the low binding affinity for thyroid hormones [26]. Aborigines usually have lower T4 levels, but have normal TSH levels and normal or borderline T3 levels. Because Aborigines do not show any clinical symptoms of hypothyroidism, the homeostasis of thyroid hormone physiology in Aborigines differs from that in other human populations.
Although the adaptive significance of the variations remain elusive in the above cases, some interpopulation variation may result from adaptive evolution to divergent environments. Serum free T4 levels are higher in indigenous Evenki women than in nonindigenous Russian women living in the same communities in central Siberia [27]. The variation in free T4 levels was correlated with the variation in basal metabolic rate both in Evenki and Russian men and women [27]. Similar cases were also found for indigenous Nenets and nonindigenous Russians: both showed significant increases in total T4 levels during winter, but the magnitude of the increase was significantly greater in the Nenets than in the Russians [27]. Because thyroid hormones play important roles in regulating metabolic rate and adaptation to cold environments [28,29], human populations inhabiting colder environments may acquire genetic basis for more efficient thyroid hormone-induced thermogenesis and may therefore be genetically adapted to cold environments [30].
Interindividual differences in TSH levels are prevalent, and have been found to be associated with variation in life span. In Ashkenazi Jews and Northern Italians, healthy oldest-old people of around 100 years of age had higher TSH levels than elderly controls of around 70 years of age [31,32]. In addition, follow-up studies revealed that participants with abnormally high TSH levels had a lower mortality rate than those with normal or low TSH levels [33]. The offspring of Ashkenazi Jewish centenarians had significantly higher TSH levels, suggesting that higher TSH levels and longevity have heritable components [32]; however, the molecular mechanisms of this variation are unknown.
2.2. Genetic basis for variation
In addition to the case of TGB in Australian Aborigines [34], polymorphisms associated with variation in thyroid hormone physiology have been found in other populations [35]. Several studies have focused on candidate genes involved in thyroid hormone signaling pathways and revealed that single nucleotide polymorphisms (SNPs) of the TSH receptor (
If genes involved in thyroid hormone pathways were targets of natural selection, we would be able to find some signatures of natural selection in the human genome. When natural selection increases the frequency of a new beneficial mutation in a population, the neighboring regions will reduce the genetic variation and increase the level of linkage disequilibrium [42]. Two genes involved in the thyroid hormone pathway, thyroid hormone receptor interactor 4 (
The high rate of nonsynonymous (amino acid–altering) changes compared with the rate of synonymous (silent) changes also indicates that the genes might be under positive selection [42]. By comparing the synonymous and nonsynonymous substitutions in the human and chimp genomes, putatively positively selected genes were screened [46]. Genes expressed in the thyroid gland have an excess of rapidly evolving genes compared with other tissues, except testis, which has more putatively positively selected genes [46]. Changes in thyroid hormone physiology may contribute to some of the physiological and morphological divergence between humans and apes [47,48].
3. Inter-population and geographical variation in thyroid hormone physiology in animals
Anatomical studies conducted in the 1960s and 1970s showed interspecies morphological variation for fishes and amphibians [49,50]. Since then, natural variation in thyroid hormone physiology has been extensively investigated in diverse taxa of vertebrate (Table 1). Some of the variation results from environmental factors. For example, environmental contaminants can cause goiter. In salmon populations introduced into the Great Lakes in the late 1960s, the frequency of thyroid goiter increased in the mid-1970s [51,52,53]. In addition, herring gulls
Species/Family | Phenotypic variation | Potential factors and functions | Reference |
Intraspecific variation | |||
Coho salmon | Goiter, T4, T3 | Goitrogen | [51,53,97] |
Chinook salmon | Goiter | Goitrogen | [53] |
Herring gull | Goiter | Goitrogen | [54] |
American alligator | T4 | Goitrogen | [98] |
Japanese pond frog | Morphology | [49] | |
Bottlenose dolphin | T4 and T3 | Temperature | [62] |
Northern cardinal | T4 and T3 | [61] | |
Alaskan husky | T4 and T3 | Temperature | [60] |
Bonnethead shark | T4 and T3 in yolk | Temperature | [70] |
Brook charr | T4 and T3 | Migration | [87] |
Stickleback | Goiter, TSHß, T4,T3 | Migration, metabolism | [57,58,86] |
Interspecific variation | |||
Poeciliidae | Morphology, tumor | [50,99,100] | |
Spadefoot toad | T4, T3, sensitivity | Dry environment, metamorphosis | [63] |
Big-eared mouse | T4, T3, iodide | Low iodide concentration | [59] |
Rodent | T4 | Life span | [101] |
Goiters were also observed in hatchery fishes and possibly resulted from iodine deficiency, because iodine treatment was able to cure the goiter [56]. In the case of the threespine stickleback
Latitudinal variation in plasma concentrations of thyroid hormone has been observed in both mammals and birds, and these variations might have evolved as adaptations to environments with divergent temperatures. Plasma total T4, free T4, and total T3 levels of sled dogs living in Alaska were higher than dogs in New York, especially in winter [60]. In addition, plasma T3 increased with increasing latitude in the northern cardinals
Several studies have demonstrated that variation in thyroid hormone physiology correlates with other potentially adaptive traits. Interspecies variation in tissue thyroid hormone levels and tissue sensitivity to thyroid hormone may be correlated with variation in the duration of the larval period in spadefoot toads [63]. For example, the tadpole of the desert-dwelling toad
Thyroid hormones also play critical roles as yolk hormones in mammalian [66], bird [67], and teleost [68,69] development. In the bonnethead shark
Thyroid hormone is also implicated in the regulation of longevity in animals [74,75]. Long-lived species of squirrels, deer mice, bats and mole-rats maintain low levels of thyroid hormone [76,77,78,79]. Hypothyroid Wister rats live longer than hyperthyroid rats [80]. Furthermore, investigations in the Ames and Snell dwarf mice have demonstrated that mutation at the
Divergence in thyroid hormone physiology may also be important for adaptation of stickleback fishes to marine and freshwater environments [86]. Stream-resident populations of the threespine stickleback have repeatedly evolved from ancestral marine populations. First, Kitano et al. (2010) found plasma thyroid hormone levels and metabolic rate were lower in stream-resident populations than in ancestral marine populations [86]. Since thyroid hormones regulate metabolic rate in sticklebacks [86], it is likely that lower thyroid hormone in stream-resident sticklebacks is adaptive for permanent residency in small streams where oxygen and food are often scarce. In addition, the expression level of thyroid stimulating hormone
Other than the
4. Conclusions and future directions
We found similar features in the patterns of variation in thyroid hormone physiology in humans and other animals. First, genetic variation in the susceptibility to endemic goiter exists among populations and species. Second, some of the latitudinal and racial variation in thyroid hormone physiology likely results from adaptation to environments with divergent ambient temperatures. Third, variation in thyroid hormone physiology may be associated with variation in longevity. Fourth, genomic scan of signatures of selection have revealed that some thyroid hormone-related genes experience selective pressure during evolution or domestication.
In humans, it is very difficult to experimentally test the adaptive significance of such variation. However, ecological experiments can be conducted using animals. For example, reciprocal transplant experiments on divergent populations or species with different thyroid hormone physiology can test whether wild animals have higher fitness in native habitats than in foreign habitats [95,96]. We can also investigate whether the fitness is correlated with the thyroid hormone levels. In addition, hormonal manipulation would be able to directly test whether the higher or lower thyroid hormone levels can change the fitness in a variety of environments.
Until recently, it has been difficult to study the genetic basis for physiological differences between natural animal populations. However, it is now becoming increasingly easier to conduct genomic studies because of the recent progress in genomic technologies. Therefore, we can test whether candidate loci involved in thyroid hormone signaling pathways are correlated with fitness in natural environments or laboratory conditions. Furthermore, ecological and genomic studies of wild animal populations will help answer fundamental evolutionary questions, such as whether the same environmental variables are strong agents of natural selection on the thyroid hormone pathways and whether genetic variation in the same genes caused the adaptive divergence in thyroid hormone physiology across diverse taxa, including humans.
AcknowledgementThis research is supported by JST PRESTO program, the Naito Foundation, Grant-in-Aid for Scientific Research on Innovative Areas (23113007 and 23113001) from the Ministry of Education, Science, Sports, and Culture to JK. AI is a Fellow of the Japan Society of Promotion of Science.
References
- 1.
Park SM, Chatterjee VKK 2005 Genetics of congenital hypothyroidism. J Med Genet42 379 389 - 2.
Grasberger H. Refetoff S. 2011 Genetic causes of congenital hypothyroidism due to dyshormonogenesis. Curr Opin Pediatr23 421 428 - 3.
Rastogi MV, LaFranchi SH 2010 Congenital hypothyroidism. Orphanet J Rare Dis 5: 17. - 4.
Grüters A. Krude H. Biebermann H. 2004 Molecular genetic defects in congenital hypothyroidism. Eur J Endocrinol 151: U39 U44. - 5.
Moreno J. C. de Vijlder J. J. M. Vulsma T. Ris-Stalpers C. 2003 Genetic basis of hypothyroidism: recent advances, gaps and strategies for future research. Trends Endocrinol Metab14 318 326 - 6.
Hébrant A. van Staveren V. C. G. Maenhaut C. Dumont J. E. Leclère J. 2011 Genetic hyperthyroidism: hyperthyroidism due to activating TSHR mutations. Eur J Endocrinol164 1 9 - 7.
Prummel M. F. Strieder T. Wiersinga W. M. 2004 The environment and autoimmune thyroid diseases. Eur J Endocrinol150 605 618 - 8.
Tomer Y. 2010 Genetic susceptibility to autoimmune thyroid disease: past, present, and future. Thyroid20 715 725 - 9.
Landa I. Robledo M. 2011 Association studies in thyroid cancer susceptibility: are we on the right track? J Mol Endocrinol 47: R43 R58 - 10.
Selinus O. Alloway B. Centeno J. A. Finkelman R. B. Fiuge R. et al. 2005 Essentials of Medical Geology. Burlington: Elsevier. - 11.
Koutras D. A. Matovinovic J. Vought R. 1985 The ecology of iodine. In: Stanbury JB, Hetzel BS, editors. Endemic Goitre and Cretinism, Iodine Nutrition in Health and Disease. New York: Wiley.185 195 - 12.
Davenport CB 1932 The genetical factor in endemic goiter. Lancaster: Lancaster Press. - 13.
Böttcher Y. Eszlinger M. Tönjes A. Paschke R. 2005 The genetics of euthyroid familial goiter. Trends Endocrinol Metab16 314 319 - 14.
Singer J. Eszlinger M. Wicht J. Paschke R. 2011 Evidence for a more pronounced effect of genetic predisposition than environmental factors on goitrogenesis by a case control study in an area with low normal iodine supply. Horm Metab Res43 349 354 - 15.
Perez-Centeno C. Gonzalez-Sarmiento R. Mories M. T. Corrales J. J. Miralles-Garcia J. M. 1996 Thyroglobulin exon 10 gene point mutation in a patient with endemic goiter. Thyroid6 423 427 - 16.
Corral J. Martin C. Pérez R. Sánchez I. González-Sarmiento R. et al. 1993 Thyroglobulin gene point mutation associated with non-endemic simple goitre. Lancet341 462 464 - 17.
Matsuda A. Kosugi S. 1997 A homozygous missense mutation of the sodium/iodide symporter gene causing iodide transport defect. J Clin Endocrinol Metab82 3966 3971 - 18.
Neumann S. Bayer Y. Reske A. Tajtáková Paschke. R. 2003 Further indications for genetic heterogeneity of euthyroid familial goiter. J Mol Med81 736 745 - 19.
Neumann S. Willgerodt H. Ackermann F. Reske A. Jung M. et al. 1999 Linkage of familial euthyroid goiter to the multinodular goiter-1 locus and exclusion of the candidate genes thyroglobulin, thyroperoxidase, and Na+/I− symporter. J Clin Endocrinol Metab84 3750 3756 - 20.
Hollowell JG, Staehling CA, Flanders WD, Hannon WH, Gunter EW, et al. 2002 Serum TSH, T4, and thyroid antibodies in the United States population (1988 to 1994): National Health and Nutrition Examination Survey (NHANES III). J Clin Endocrinol Metab87 489 499 - 21.
Walker JA, Illions EH, Huddleston JF, Smallridge RC 2005 Racial comparisons of thyroid function and autoimmunity during pregnancy and the postpartum period. Obstet Gynecol106 1365 1371 - 22.
Surks M. I. Boucai L. 2010 Age- and race-based serum thyrotropin reference limits. J Clin Endocrinol Metab95 496 502 - 23.
Dick M. Watson F. 1980 Prevalent low serum thyroxine-binding globulin level in western Australian Aborigines. Med J Australia1 115 118 - 24.
Dick M. Watson F. 1981 A possible variant of thyroxine-binding globulin in Australian Aborigines. Clin Chim Acta116 361 367 - 25.
Takeda K. Mori Y. Sobieszczyk S. Seo H. Dick M. et al. 1989 Sequence of the variant thyroxine-binding globulin of Australian aborigines. Only one of two amino acid replacements is responsible for its altered properties. J Clin Invest83 1344 1348 - 26.
Murata Y. Refetoff S. Sarne D. H. Dick M. Watson F. 1985 Variant thyroxine-binding globulin in serum of Australian aborigines: its physical, chemical and biological properties. J Endocrinol Invest8 225 232 - 27.
Leonard WR, Sorensen MV, Galloway VA, Spencer GJ, Mosher MJ, et al. 2002 Climatic influences on basal metabolic rates among circumpolar populations. Am J Hum Biol14 609 620 - 28.
Laurberg P. Andersen S. Karmisholt J. 2005 Cold adaptation and thyroid hormone metabolism. Thieme eJournal37 545 549 - 29.
Launay-C J. Savourey G. 2009 Cold adaptations. Ind Health47 221 227 - 30.
Leonard WR, Snodgrass JJ, Sorensen MV 2005 Metaolic adaptation in indigenous Siberian populations. Ann Rev Anthropol34 451 471 - 31.
Ravaglia G. Forti P. Maioli F. Nesi B. Pratelli L. et al. 2000 Blood micronutrient and thyroid hormone concentrations in the oldest-old. J Clin Endocrinol Metab85 2260 2265 - 32.
Atzmon G. Barzilai N. Hollowell J. G. Surks M. I. Gabriely I. 2009 Extreme longevity is associated with increased serum thyrotropin. J Clin Endocrinol Metab94 1251 1254 - 33.
Gussekloo J. van Exel E. de Craen A. J. Meinders A. E. Frolich M. et al. 2004 Thyroid status, disability and cognitive function, and survival in old age. JAMA- J Am Med Assoc292 2591 2599 - 34.
J Endocrinol InvestMurata Y. Refetof S. Same D. H. Dick M. Watson F. Variant thyroxine-binding. globulin in. serum of. Australian Aborigines-its. physical chemical. biological properties. 8 225 232 - 35.
Peeters RP, van der Deure WM, Visser TJ 2006 Genetic variation in thyroid hormone pathway genes; polymorphisms in the TSH receptor and the iodothyronine deiodinases. Eur J Endocrinol155 655 662 - 36.
Peeters R. P. van Toor H. Klootwijk W. de Rijke Y. B. Kuiper G. G. et al. 2003 Polymorphism in thryoid hormone pathway genes are associated with plasma TSH and iodothyronine levels in healthy subjects. J Clin Endocrinol Metab88 2880 2888 - 37.
Panicker V. Cluett C. Shields B. Murray A. Parnell K. S. et al. 2008 A common variation in deiodinase 1 gene DIO1 is associated with the relative levels of free thyroxine and triiodothyronine. J Clin Endocrinol Metab93 3075 3081 - 38.
Alberobello A. T. Congedo V. Liu H. Cochran C. Skarulis M. C. et al. 2011 An intronic SNP in the thyroid hormone receptor beta gene is associated with pituitary cell-specific over-expression of a mutant thyroid hormone receptor beta2 (R338W) in the index case of pituitary-selective resistance to thyroid hormone. J Transl Med 9: 144. - 39.
Dayan C. M. Panicker V. 2009 Novel insights into thyroid hormones from the study of common genetic variation. Nat Rev Endocrinol5 211 218 - 40.
Horvath A. Faucz F. Finkielstain G. P. ME Nikita Rothenbuhler. A. et al. 2010 Haplotypeanalysis of the promoter region of phosphodiesterase type 8B (PDE8B) in correlation with inactivating PDE8B mutation and the serum thyroid-stimulating hormone Levels. Thyroid 20. - 41.
Arnaud-Lopez L. Usala G. Ceresini G. BD Mitchell Pilia. M. G. et al. 2008 Phosphodiesterase 8B gene variants are associated with serum TSH levels and thyroid function. Am J Hum Genet82 1270 1280 - 42.
Sabeti P. C. Schaffner S. F. Fry B. Lohmueller J. Varilly P. et al. 2006 Positive natural selection in the human lineage. Science312 1614 1620 - 43.
López Herráez. D. Bauchet M. Tang K. Theunert C. Pugach I. et al. 2010 Genetic variation and recent positive selection in worldwide human populations: evidence from nearly 1 million SNPs. PLoS One 4: e7888. - 44.
Dormitzer PR, Ellison PT, Bode HH 1989 Anomalously low endemic goiter prevalence among Efe pygmies. Am J Phys Anthropol78 527 531 - 45.
Hancock A. M. Witonsky D. B. Alkorta-Aranburu G. Beall C. M. Gebremedhin A. et al. 2011 Adaptations to climate-mediated selective pressures in humans. PLoS Genet 7: e1001375. - 46.
Nielsen R. Bustamante C. Clark A. G. Glanowski S. Sackton T. B. et al. 2005 A scan for positively selected genes in the genomes of humans and chimpanzees. PLoS Biol 3: e170. - 47.
Gagneux P. Amess B. Diaz S. Moore S. Patel T. et al. 2001 Proteomic comparison of human and great ape blood plasma reveals conserved glycosylation and differences in thyroid hormone metabolism. Am J Phys Anthropol115 99 109 - 48.
Newton P. 1996 Hypothyroid nails and evolution. Lancet347 1832 1833 - 49.
Iwasawa H. 1960 On the local variation of the thyroid gland in the Japanese pond frog, Rana nigromaculata. Doubutsugaku zasshi69 125 128 - 50.
Woodhead AD, Scully PM 1977 A comparative study of the Pretumorous thyroid gland of the gynogenetic teleost, Poecilia formosa, and that of other Poeciliid fishes. Cancer Res37 3751 3755 - 51.
Moccia RD, Leatherland JF, Sonstegard RA 1977 Increasing frequency of thyroid goiters in Coho salmon (Oncorhynchus kisutch) in the Great Lakes. Science198 425 426 - 52.
Sonstegard RA 1976 Studies of the etiology and epizootiology of lymphosarcoma in Esox (Esox lucius L. and Esox masquinongy). Prog Exp Tumor Res20 141 155 - 53.
Moccia RD, Leatherland JF, Sonstegard RA 1981 Quantitative interlake comparison of thyroid pathology in Great Lakes coho (Oncorhynchus kisutch) and chinook (Oncorhynchus tschawytscha) salmon. Cancer Res41 2200 2210 - 54.
Moccia R. D. Fox G. A. Britton A. 1986 A quantitative assessment of thyroid histopathology of herring gulls (Larus argentatus) from the Great Lakes and a hypothesis on the causal role of environmental contaminants. J Wildlife Dis22 60 70 - 55.
Sonstegard RA, Leatherland JF 1979 Hypothyroidism in rats fed Great Lakes coho salmon. Bull Environ Contam Toxicol22 779 784 - 56.
Schlumberger HG 1955 Spontaneous goiter and cancer of the thyroid in animals. Ohio J Sci55 23 43 - 57.
Honma Y. Shioda S. Yoshie S. 1977 Changes in the thyroid gland associated with the diadromous migration of the threespine stickleback, Gasterosteus aculeatus. Jpn J Ichthyol24 17 25 - 58.
Hamada K. 1975 Excessively enlarged thyroid follicles of the threespine stickleback, Gasterosteus aculeatus aculeatus, reared in freshwater. Jpn J Ichthyol21 183 190 - 59.
Cabello G. Vilaxa A. Spotorno A. E. Valladares J. P. Pickard M. et al. 2003 Evolutionary adaptation of a mammalian species to an environment severely depleted of iodide. Pflug Arch Eur J Phy446 42 45 - 60.
Dunlap KL, Reynolds AJ, Refsal KR, Kerr WW, Duffy LK 2008 Cross-latitudinal, seasonal and diurnal comparisons in thyroid hormone concentrations in sled dogs. Am J Anim Vet Sci3 96 103 - 61.
Burger MF, Denver RJ 2001 Plasma thyroid hormone concentrations in a wintering passerine bird: their relationship to geographic variation, environmental factors, metabolic rate, and body fat. Physiol Biochem Zool75 187 199 - 62.
Fair P. A. Montie E. Balthis L. Reif J. S. Bossart G. D. 2011 Influences of biological variables and geographic location on circulating concentrations of thyroid hormones in wild bottlenose dolphins (Tursiops truncatus). Gen Comp Endocrinol174 184 194 - 63.
Buchholz DR, Hayes TB 2005 Variation in thyroid hormone action and tissue content underlies species differences in the timing of metamorphosis in desert frogs. Evol Dev7 458 467 - 64.
Bragg AN 1945 The spadefoot toads in Oklahoma with a summary of our knowledge of the group. II. Am Nat79 52 72 - 65.
Newman RA 1988 Genetic variation for larval anuran (Scaphiopus couchii) development time in an uncertain environment. Evolution42 763 773 - 66.
Pickard MR, Sinha AK, Ogilvie LM, Leonard AJ, Edwards PR, et al. 1999 Maternal hypothyroxinemia influences glucose transporter expression in fetal brain and placenta. J Endocrinol163 385 394 - 67.
Wilson CM, McNabb FM 1997 Maternal thyroid hormones in Japanese quail eggs and their influence on embryonic development. Gen Comp Endocrinol107 153 165 - 68.
Brown DD 1997 The role of thyroid hormone in zebrafish and axolotl development. Proc Natl Acad Sci USA94 13011 13016 - 69.
Tagawa M. Hirano T. 1987 Presence of thyroxine in eggs and changes in its content during early development of chum salmon, Oncorhynchus keta. Gen Comp Endocrinol68 129 135 - 70.
Mc Comb D. M. Gelsleichter J. CA Manire Brinn. R. Brown C. L. 2005 Comparative thyroid hormone concentration in maternal serum and yolk of the bonnethead shark (Sphyrna tiburo) from two sites along the coast of Florida. Gen Comp Endocrinol144 167 173 - 71.
Parsons GR 1993 Geographic variation in reproduction between two populations of the bonnethead shark, Sphyma tiburo. Environ Biol Fish38 25 35 - 72.
Arendt JD 1997 Adaptive intrinsic growth rates: an integration across taxa. Q Rev Biol72 149 177 - 73.
Conover DO 1990 The relationship between capacity for growth and length of growing season: evidence for and implications of countergradient variation. Trans Am Fish Soc119 416 430 - 74.
Habra M. Sarlis N. J. 2005 Thyroid and aging. Rev Endocr Metab Disord6 145 154 - 75.
Brown-Borg HM 2007 Hormonal regulation of longevity in mammals. Ageing Res Rev6 28 45 - 76.
Hulbert AJ, Hinds DS, MacMillen RE 1985 Minimal metabolism, summit metabolism and plasma thyroxine in rodents from different environments. Comp Biochem Phys A81 687 693 - 77.
Kwiecinski GG, Damassa DA, Gustafson AW 1986 Control of sex steroid-binding protein (SBP) in the male little brown bat: relationship of plasma thyroxine levels to the induction of plasma SBP in immature males. J Endocrinol110 271 278 - 78.
Buffenstein R. 2005 The naked mole-rat: a new long-living model for human aging research. J Gerontol A Biol Sci Med Sci60 1369 1377 - 79.
Buffenstein R. Woodley R. Thomadakis C. Daly T. J. Gray D. A. 2001 Cold-induced changes in thyroid function in a poikilothermic mammal, the naked mole-rat. Am J Physiol-Reg I 280: R149 155 - 80.
Ooka H. Shinkai T. 1986 Effects of chronic hyperthyroidism on the lifespan of the rat. Mech Ageing Dev33 275 282 - 81.
Lin S. C. Li S. Drolet D. W. Rosenfeld M. G. 1994 Pituitary ontogeny of the Snell dwarf mouse reveals Pit-1-independent and Pit-1-dependent origins of the thyrotrope. Development120 515 522 - 82.
Sornson M. W. Wu W. Dasen J. S. Flynn S. E. Norman D. J. et al. 1996 Pituitary lineage determination by the Prophet of Pit-1 homeodomain factor defective in Ames dwarfism. Nature384 327 333 - 83.
Boylston W. H. De Ford J. H. Papaconstantinou J. 2006 Identification of longevity-associated genes in long-lived Snell and Ames dwarf mice. Age28 125 144 - 84.
Vergara M. Smith-Wheelock M. Harper J. M. Sigler R. Miller R. A. 2004 Hormone-treated snell dwarf mice regain fertility but remain long lived and disease resistant. J Gerontol A Biol Sci Med Sci59 1244 1250 - 85.
Hauck S. J. Hunter W. S. Danilovich N. Kopchick J. J. Bartke A. 2001 Reduced levels of thyroid hormones, insulin, and glucose, and lower body core temperature in the growth hormone receptor/binding protein knockout mouse. Exp Biol Med226 552 558 - 86.
Kitano J. Lema S. C. Luckenbach J. A. Mori S. Kawagishi Y. et al. 2010 Adaptive divergence in the thyroid hormone signaling pathway in the stickleback radiation. Curr Biol20 2124 2130 - 87.
Boura D. Castric V. Bernatchez L. Audet C. 2002 Physiological, endocrine, and genetic bases of anadromy in the brook charr, Salvelinus fontinalis, of the Laval River (Que ́bec, Canada). Environ Biol Fish64 229 242 - 88.
Rubin C. J. Zody M. C. Eriksson J. Meadows J. R. Sherwood E. et al. 2010 Whole-genome resequencing reveals loci under selection during chicken domestication. Nature464 587 591 - 89.
Kijas J. W. Lenstra J. A. Hayes B. Boitard S. Porto Neto. L. R. et al. 2012 Genome-wide analysis of the world’s sheep breeds reveals high levels of historic mixture and strong recent selection. PLoS Biol 10: e1001258. - 90.
Nakao N. Ono H. Yamamura T. Anraku T. Takagi T. et al. 2008 Thyrotrophin in the pars tuberalis triggers photoperiodic response. Nature452 317 322 - 91.
Ono H. Hoshino Y. Yasuo S. Watanabe M. Nakane Y. et al. 2008 Involvement of thyrotropin in photoperiodic signal transduction in mice. Proc Natl Acad Sci U S A105 18238 18242 - 92.
Hanon E. A. Lincoln G. A. Fustin J. M. Dardente H. Masson-Pevet M. et al. 2008 Ancestral TSH mechanism signals summer in a photoperiodic mammal. Curr Biol18 1147 1152 - 93.
Masumoto K. Ukai-Tadenuma M. Kasukawa T. Nagano M. Uno K. D. et al. 2010 Acute induction of Eya3 by late-night light stimulation triggers TSHβ expression in photoperiodism. Curr Biol20 2199 2206 - 94.
Dardente H. CA Wyse Birnie. MJ Dupré S. M. Loudon A. S. I. et al. 2010 A molecular switch for photoperiod responsiveness in mammals. Cur Biol20 1193 2198 - 95.
Schluter D. 2000 The Ecology of Adaptive Radiation. New York: Oxford University Press. - 96.
Barrett RDH, Hoekstra HE 2011 Molecular spandrels: tests of adaptation at the genetic level. Nat Rev Genet12 767 780 - 97.
Sonstegard R. Leatherland J. F. 1976 The epizootiology and pathogenesis of thyroid hyperplasia in coho salmon (Oncorhynchus kisutch) in Lake Ontario. Cancer Res36 4467 4475 - 98.
Hewitt EA, Crain DA, Gunderson MP, Guillette LJJ 2002 Thyroid status in juvenile alligators (Alligator mississippiensis) from contaminated and reference sites on Lake Okeechobee, Florida, USA. Chemosphere47 1129 1135 - 99.
Gorbman A. Gordon M. 1951 Spontaneous thyroidal tumors in the swordtail Xiphophorus montezumae. Cancer Res11 184 187 - 100.
Berg O. Gordon M. Gorbman A. 1954 Comparative effects of thyroidal stimulants and inhibitors of normal and tumorous thyroids in Xiphophorin fishes. Cancer Res14 527 533 - 101.
Buffernstein R. Pinto M. 2009 Endocrine function in naturally long-living small mammals. Mol Cell Endocrinol299 101 111