REGULAR ARTICLE Involvement of growth hormone-insulin-like growth factor I system in cranial remodeling during halibut metamorphosis as indicated by tissue- and stage-specific receptor gene expression and the presence of growth hormone receptor protein Jon Hildahl & Deborah M. Power & Björn Thrandur Björnsson & Ingibjörg Eir Einarsdóttir Received: 15 August 2007 / Accepted: 19 December 2007 / Published online: 12 March 2008 # Springer-Verlag 2007 Abstract The role of growth hormone (GH) and insulin- like growth factor-I (IGF-I) in the tissue remodeling associated with the transition of a symmetrical larva to an asymmetrical juvenile during flatfish metamorphosis is unknown. In order to investigate the potential role of these hormones in the remodeling of cranial bone and soft tissue that accompanies eye migration during metamorphosis of Atlantic halibut (Hippoglossus hippoglossus) larvae, tissue- specific gene expression was monitored by in situ hybrid- ization for Atlantic halibut type I growth hormone receptor (hhGHR), type II hhGHR, and insulin-like growth factor-I receptor (hhIGF-IR). Polyclonal antibody generated against the extracellular domain of type I hhGHR was used for the immunohistochemical localization of type I GHR protein. Type I hhGHR, type II hhGHR, and hhIGF-IR mRNA were expressed in fibroblasts, frontal bone osteocytes, and dorsal chondrocytes at the onset of metamorphosis (stage 8), during metamorphic climax (stage 9), and in fully meta- morphosed juveniles (stage 10). Type I GHR protein showed similar expression patterns to those of type I hhGHR mRNA, except in chondrocytes in which little GHR protein was detected. The localization of GHR and IGF-IR transcripts and GHR protein in cranial structures that undergo remodeling is intriguing and suggests that, in addition to thyroid hormones, the GH-IGF-I system is involved in morphological transformations during meta- morphosis in Atlantic halibut. Keywords Growth hormone receptor . Insulin-like growth factor-I receptor . Larval development . Atlantic halibut, Hippoglossus hippoglossus (Teleostei) Introduction The metamorphosis of flatfish is a dynamic process trans- forming pelagic and symmetric pre-metamorphic larvae into asymmetric metamorphosed juveniles suited for habitat transition to a benthic environment. During metamorphosis, the skin (Campinho et al. 2007b), gastrointestinal system (Miwa et al. 1992), nervous system (Osse and Van den Boogaart 1997), musculo-skeletal system (Campinho et al. 2007a; Saele et al. 2006), and osmoregulatory tissues (see Schreiber 2001) undergo major changes. In Atlantic halibut (Hippoglossus hippoglossus), migration of the ethmoid plate toward the ocular side and subsequent remodeling of the frontal plate together with fibroblast proliferation are suggested to drive eye migration, a major event leading to asymmetry (Saele et al. 2006). This process appears to involve both ossification and resorption as revealed by Cell Tissue Res (2008) 332:211–225 DOI 10.1007/s00441-007-0568-2 This work was carried out within the project “Arrested development: the molecular and endocrine basis of flatfish metamorphosis” (Q5RS- 2002-01192) with financial support from the Commission of the European Communities. However, it does not necessarily reflect the Commission’ s views and in no way anticipates its future policy in this area. This project was further supported by the Swedish Council for Agricultural and Forestry Research (FORMAS) and the Helge Ax:son Johnsons Foundation. J. Hildahl (*) : B. T. Björnsson : I. E. Einarsdóttir Fish Endocrinology Laboratory, Department of Zoology/Zoophysiology, Göteborg University, Box 436, S-40530 Göteborg, Sweden e-mail: jon.hildahl@veths.no D. M. Power Centro de Ciências de MAR, University of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal J. Hildahl (*) I B. Th. Björnsson I I. E. Einarsdóttir