VALVERDE, R.A.*; DENVER, R.J.: Molecular Evolution of the Corticotropin-Releasing Hormone Binding Protein
Corticotropin-releasing hormone (CRH) is the primary neuroendocrine mediator of the stress response in vertebrates. CRH is known to regulate appetite, locomotion, reproductive processes, and development, either by acting within the central nervous system or by functioning as a hypophysiotropin, regulating the production of adrenal steroids and thyroid hormone. A high affinity, specific CRH binding protein (CRHBP) has been identified in several mammalian species and in the amphibian Xenopus laevis. The protein exhibits extensive structural and functional conservation among the taxa studied to date. The CRHBP is thought to regulate the bioavailability of CRH by competing for binding with CRH receptors. Using a crosslinking, competitive binding assay we report the detection of the CRHBP in the brain of an agnathan fish the sea lamprey (Petromyzon marinus), a teleost fish, the tilapia (Oreochromis mossambicus), a chelonian reptile, the red-eared slider turtle (Trachemys scripta), and a bird, the chicken (Gallus domesticus). The CRHBP in these taxa reversibly binds [125I]-Xenopus CRH as does the frog binding protein. In an effort to understand the molecular evolution of this key neuroendocrine regulatory protein we are currently cloning and sequencing CRHBP cDNAs from several vertebrates. Our current data show that the CRHBP is a phylogenetically ancient protein and suggest that the regulatory role of CRHBP for the CRH peptide arose early in animal evolution.(Supported by NSF grant IBN9974672 to RJD; RAV was supported by a NIH training grant administered by the Center for Organogenesis, Univ. of Michigan)
