Molecular mechanisms of corticosteroid synergy with thyroid hormone during tadpole metamorphosis

Abstract

Corticosteroids (CS) act synergistically with thyroid hormone (TH) to accelerate amphibian metamorphosis. Earlier studies showed that CS increase nuclear 3,5,3′-triiodothyronine (T3) binding capacity in tadpole tail, and 5′ deiodinase activity in tadpole tissues, increasing the generation of T3 from thyroxine (T4). In the present study we investigated CS synergy with TH by analyzing expression of key genes involved in TH and CS signaling using tadpole tail explant cultures, prometamorphic tadpoles, and frog tissue culture cells (XTC-2 and XLT-15). Treatment of tail explants with T3 at 100 nM, but not at 10 nM caused tail regression. Corticosterone (CORT) at three doses (100, 500, 3400 nM) had no effect or increased tail size. T3 at 10 nM plus CORT caused tails to regress similar to 100 nM T3. Thyroid hormone receptor beta (TRβ) mRNA was synergistically upregulated by T3 plus CORT in tail explants, tail and brain in vivo, and tissue culture cells. The activating 5′ deiodinase type 2 (D2) mRNA was induced by T3 and CORT in tail explants and tail in vivo. Thyroid hormone increased expression of glucocorticoid (GR) and mineralocorticoid receptor (MR) mRNAs. Our findings support that the synergistic actions of TH and CS in metamorphosis occur at the level of expression of genes for TRβ and D2, enhancing tissue sensitivity to TH. Concurrently, TH enhances tissue sensitivity to CS by upregulating GR and MR. Environmental stressors can modulate the timing of tadpole metamorphosis in part by CS enhancing the response of tadpole tissues to the actions of TH.

Developmental Profiles and Thyroid Hormone Regulation of Brain Transcripts in Frogs: A Species Comparison with Emphasis on <i>Physalaemus</i> <i>pustulosus</i>

“…5 e) . On the other hand, the positive regulation of P. pustulosus dio2 mRNA by T3 is similar to what has been observed in other anurans [Brown, 2005;Hogan et al, 2007;Bonett et al, 2010;. Since endogenous THs increase during metamorphosis [Tata, 2006], comparing the developmental profiles and T3 regulation helps us elucidate whether endogenous THs are important regulators of gene expression.…”

Stress hormones mediate predator-induced phenotypic plasticity in amphibian tadpoles

“…Because chronic predator exposure increased whole-body CORT, and prior work from our laboratory showed increased tail muscle depth in R. pipiens tadpoles following treatment with CORT [39,41], we hypothesized that the elevated CORT was causal for the induced anti-predator morphology. Here, we provide compelling evidence that the increased tail size in tadpoles chronically exposed to predator chemical cue is caused by direct actions of the stress hormone CORT on the tadpole tail.…”

How Metamorphosis Is Different in Plethodontids: Larval Life History Perspectives on Life-Cycle Evolution

“…The HPT and HPI axes interact in complex ways to influence development, growth, and metamorphosis (Kulkarni and Buchholz 2012). For example, the release of corticosterone (CORT) from the interrenal glands can alter the effects of TH on morphogenesis and synergistically influence the rate of metamorphosis (Kikuyama et al 1983; Bonett et al 2010). The utility of cross-talk between these axes allows aquatic larvae under environmental stress to accelerate its transition to land.…”