BOORSE, GC; DENVER, RJ; University of Michican, Ann Arbor: A functional corticotropin-releasing hormone signaling system in Xenopus tadpole tail
Corticotropin-releasing hormone (CRH) is the principal neurohormone regulating the hypothalamo-pituitary-adrenal axis. However, the distribution and actions of CRH are not limited to the neuroendocrine system. In mammals and frogs several peripheral tissues are known to express components of the CRH signaling system, but the functional significance of this expression is poorly understood. We have been studying the Xenopus tadpole tail as a peripheral site of CRH expression and action. We have shown that CRH, CRH-receptors and CRH binding protein (CRH-BP) are all expressed in the tadpole tail. We also have evidence that CRH exerts a cytoprotective effect on the tadpole tail, inhibiting spontaneous tail regression in tissue explant cultures. To further characterize the role of CRH in the tadpole tail, we analyzed CRH expression and action in a Xenopus tadpole tail muscle-derived cell line (XLT-15). We detected mRNAs by RT-PCR for both CRH and CRH receptor type 1 (CRH-R1) in XLT-15 cells. By contrast, CRH-R2 and CRH-BP mRNAs were not expressed. CRH peptide content in XLT-15 cells was similar to that of tadpole tail tissue as determined by tissue extraction and radioimmunoassay. Treatment of XLT-15 cells with CRH (100 nM) increased intracellular cAMP levels 7.5 fold by ten minutes after exposure. This action of CRH was blocked by co-incubation with two different CRH-receptor antagonists (either αhel-CRH9-41 or antalarmin), thus supporting the existence of functional CRH receptors on these cells. Our findings support the presence of a functional CRH signaling system in Xenopus tadpole tail, and suggest that the peptide may play a role as a growth or cell survival factor (supported by NSF grant IBN 9974672 to RJD and NSF predoctoral fellowship to GCB)
