Upon metamorphosis amphibian tadpoles lose their tails through programmed cell death induced by thyroid hormone (T 3 ). Before transformation the tail functions as an essential locomotory organ. The binding protein for the stress neuropeptide corticotropinreleasing factor (CRF; CRF-BP) is strongly upregulated in the tail of Xenopus tadpoles during spontaneous or T 3 -induced metamorphosis. This finding led us to investigate physiological roles for CRF and CRF-BP in tadpole tail. We found CRF,

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... F-BP and functional CRF 1 receptor in tail, and CRF and functional CRF 1 receptors, but not CRF-BP in the tail muscle-derived cell line XLT-15. CRF, acting via the CRF 1 receptor, slowed spontaneous tail regression in explant culture, and caused a reduction in caspase 3/7 activity. CRF increased, but stable CRF-BP overexpression decreased [ 3 H]-thymidine incorporation in XLT-15 cells. Overexpression of CRF-BP in vivo accelerated the loss of tail muscle cells during spontaneous metamorphosis. Lastly, exposure of tail explants to hypoxia increased CRF and urocortin 1, but strongly decreased CRF-BP mRNA expression. We show that CRF is expressed in tadpole tail, is upregulated by environmental stressors, and is cytoprotective. The inhibitory binding protein for CRF is regulated by hormones or by environmental stressors and can modulate CRF bioactivity.