Corticosterone Is Essential for Survival Through Frog Metamorphosis

Shewade, Leena; Schoephoerster, Jamee; Patmann, Matthew D; Kulkarni, Saurabh S.; Buchholz, Daniel R.

doi:10.1210/endocr/bqaa193

Cited by 18 publications

(18 citation statements)

References 59 publications

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“…Therefore, we provide evidence that upregulation of circulating levels of CORT and GC receptors play roles in enhancing the survival of larval amphibians exposed to salinity. CORT‐dependent increases in thyroid hormone are necessary for organ development and survival through metamorphosis (Shewade et al, 2020), and CORT expedites the development of larval amphibians in unfavorable conditions (Denver, 1999; Hayes & Wu, 1994). Although most studies of survival focus on metamorphosing amphibians, our study demonstrates that CORT directly enhances survival for larvae exposed to increased salinity, a chronic anthropogenic stressor.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Corticosterone mediates a growth‐survival tradeoff for an amphibian exposed to increased salinity

et al. 2021

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Life‐history tradeoffs are common across taxa, but growth‐survival tradeoffs—usually enhancing survival at a cost to growth—are less frequently investigated. Increased salinity (NaCl) is a prevalent anthropogenic disturbance that may cause a growth‐survival tradeoff for larval amphibians. Although physiological mechanisms mediating tradeoffs are seldom investigated, hormones are prime candidates. Corticosterone (CORT) is a steroid hormone that independently influences survival and growth and may provide mechanistic insight into growth‐survival tradeoffs. We conducted a 24‐day experiment to test effects of salinity (<32–4000 mg/L) on growth, development, survival, CORT responses, and tradeoffs among traits of larval Northern Leopard Frogs (Rana pipiens). We also experimentally suppressed CORT signaling to determine whether CORT signaling mediates effects of salinity and a growth‐survival tradeoff. Increased salinity reduced survival, growth, and development. Suppressing CORT signaling in conjunction with salinity reduced survival further but also attenuated the negative effects of salinity on growth, development, and water content. CORT of control larvae increased or was stable with growth and development but decreased with growth and development for those exposed to salinity. Therefore, salinity dysregulated CORT physiology. Across all treatments, larvae that survived had higher CORT than larvae that died. By manipulating CORT signaling, we provide strong evidence that CORT physiology mediates the outcome of a growth‐survival tradeoff and enhances survival. To our knowledge, this is the first study to concomitantly measure tradeoffs between growth and survival and experimentally link these changes to CORT physiology. Identifying mechanistic links between stressors and fitness‐related outcomes is critical to enhance our understanding of tradeoffs.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Corticosterone mediates a growth‐survival tradeoff for an amphibian exposed to increased salinity

et al. 2021

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“…Recent work from Dan Buchholz's laboratory in which they inactivated the gene that codes for GR using CRISPR/Cas9 genome editing in X. tropicalis showed that GR is essential for survival through metamorphosis ( Sterner et al, 2020 ). This same group inactivated the gene that codes for proopiomelanocortin, the precursor for ACTH and other bioactive peptides, and found that the tadpoles did not survive metamorphosis, but this defect could be rescued by treatment with CORT ( Shewade et al, 2020 ).…”

Section: Neuroendocrine Control Of Amphibian Metamorphosismentioning

confidence: 99%

Stress hormones mediate developmental plasticity in vertebrates with complex life cycles

Denver

2021

Neurobiology of Stress

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The environment experienced by developing organisms can shape the timing and character of developmental processes, generating different phenotypes from the same genotype, each with different probabilities of survival and performance as adults. Chordates have two basic modes of development, indirect and direct. Species with indirect development, which includes most fishes and amphibians, have a complex life cycle with a free-swimming larva that is typically a growth stage, followed by a metamorphosis into the adult form. Species with direct development, which is an evolutionarily derived developmental mode, develop directly from embryo to the juvenile without an intervening larval stage. Among the best studied species with complex life cycles are the amphibians, especially the anurans (frogs and toads). Amphibian tadpoles are exposed to diverse biotic and abiotic factors in their developmental habitat. They have extensive capacity for developmental plasticity, which can lead to the expression of different, adaptive morphologies as tadpoles (polyphenism), variation in the timing of and size at metamorphosis, and carry-over effects on the phenotype of the juvenile/adult. The neuroendocrine stress axis plays a pivotal role in mediating environmental effects on amphibian development. Before initiating metamorphosis, if tadpoles are exposed to predators they upregulate production of the stress hormone corticosterone (CORT), which acts directly on the tail to cause it to grow, thereby increasing escape performance. When tadpoles reach a minimum body size to initiate metamorphosis they can vary the timing of transformation in relation to growth opportunity or mortality risk in the larval habitat. They do this by modulating the production of thyroid hormone (TH), the primary inducer of metamorphosis, and CORT, which synergizes with TH to promote tissue transformation. Hypophysiotropic neurons that release the stress neurohormone corticotropin-releasing factor (CRF) are activated in response to environmental stress (e.g., pond drying, food restriction, etc.), and CRF accelerates metamorphosis by directly inducing secretion of pituitary thyrotropin and corticotropin, thereby increasing secretion of TH and CORT. Although activation of the neuroendocrine stress axis promotes immediate survival in a deteriorating larval habitat, costs may be incurred such as reduced tadpole growth and size at metamorphosis. Small size at transformation can impair performance of the adult, reducing probability of survival in the terrestrial habitat, or fecundity. Furthermore, elevations in CORT in the tadpole caused by environmental stressors cause long term, stable changes in neuroendocrine function, behavior and physiology of the adult, which can affect fitness. Comparative studies show that the roles of stress hormones in developmental plasticity are conserved across vertebrate taxa including humans.

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“…Glucocorticoids represent an ancillary endocrine influence on metamorphosis, regulating the rate at which it proceeds by altering sensitivity of target tissues to TH and modulating the expression of TH-regulated genes (Sachs and Buchholz, 2019). The significance of the role of GCs is underscored by the requirement of both CORT and GR for survival and completion of metamorphosis in Xenopus (Shewade et al, 2020;Sterner et al, 2020). Expression of several TR target genes can be induced by TCDD and other AHR agonists, and TCDD exposure can alter tail resorption and limb growth during metamorphosis (Taft, et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Dioxin Disrupts Thyroid Hormone and Glucocorticoid Induction of klf9, a Master Regulator of Frog Metamorphosis

Han

Zhao

Powell

2021

Preprint

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Frog metamorphosis, the development of an air-breathing froglet from an aquatic tadpole, is controlled by thyroid hormone (TH) and glucocorticoids (GC). Metamorphosis is susceptible to disruption by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), an aryl hydrocarbon receptor (AHR) agonist. Krüppel-Like Factor 9 (klf9), an immediate early gene in the endocrine-controlled cascade of expression changes that govern metamorphosis, can be synergistically induced by both hormones. This process is mediated by an upstream enhancer cluster, the klf9 synergy module (KSM). klf9 is also an AHR target. We measured klf9 mRNA following exposures to triiodothyronine (T3), corticosterone (CORT), and TCDD in the Xenopus laevis cell line XLK-WG. klf9 was induced 6-fold by 50 nM T3, 4-fold by 100 nM CORT, and 3-fold by 175 nM TCDD. Co-treatments of CORT and TCDD or T3 and TCDD induced klf9 7- and 11-fold, respectively, while treatment with all 3 agents induced a 15-fold increase. Transactivation assays examined regulatory sequences from the Xenopus tropicalis klf9 upstream region. KSM-containing segments mediated a strong T3 response and a larger T3/CORT response, while induction by TCDD was mediated by a region ∼1 kb farther upstream containing 5 AHR response elements (AHREs). This region also supported a CORT response in the absence of readily-identifiable glucocorticoid responsive elements, suggesting mediation by protein-protein interactions. An AHRE cluster is positionally conserved in the human genome, and klf9 was induced by TCDD and TH in HepG2 cells. These results indicate that AHR binding to upstream AHREs represents an initiating event in TCDD’s disruption of klf9 expression and metamorphosis.

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Corticosterone Is Essential for Survival Through Frog Metamorphosis

Cited by 18 publications

References 59 publications

Corticosterone mediates a growth‐survival tradeoff for an amphibian exposed to increased salinity

Corticosterone mediates a growth‐survival tradeoff for an amphibian exposed to increased salinity

Stress hormones mediate developmental plasticity in vertebrates with complex life cycles

Dioxin Disrupts Thyroid Hormone and Glucocorticoid Induction of klf9, a Master Regulator of Frog Metamorphosis

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