Crosstalk between thyroid hormones and the central corticotropin-releasing factor system in Atlantic salmon

The corticotropin-releasing factor (CRF) system is primarily known for its conserved role in regulating pituitary corticotrope activity, but it can also influence thyroid hormone (TH) production by stimulating thyroid-stimulating hormone (TSH) production in non-mammalian vertebrates. However, few studies have explored how THs regulate the CRF system in teleosts. Furthermore, while the CRF system regulates corticotrope activity via a CRF receptor 1 (CRFR1) mediated pathway, the signaling pathway by which CRF stimulates TSH production in teleost thyrotropes is unknown. To better understand interactions between THs and the CRF system, we performed a series of in vivo, in vitro, and in silico analyses using Atlantic salmon (Salmo salar). We found that chronic elevation of triiodothyronine (T3) levels elicited ligand- and paralog-specific effects on transcript levels of CRF peptides in the hypothalamic and preoptic regions of the brain. Additionally, elevated T3 increased transcription of pituitary CRF receptor 2 (crfr2b) but had no effect on CRFR1 transcription. Consistent with interactions between THs and CRFR2, we found that transcription of TSH (tshba) only increased in cultured pituitaries when CRFR2 was activated. In contrast, CRFR1 activation only increased the transcription of corticotrope-related genes. Lastly, we found that putative TH response elements were present in the promoter of most CRF system components, further supporting the relationship between THs and the CRF system in teleosts. Collectively, our data reveal several novel mechanisms underlying crosstalk between THs and the central CRF system in teleost fishes and provide insight into the evolution of interactions between these hormone systems.