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Laboratory of Molecular Endocrinology, School of Fisheries Sciences, Kitasato University (H.K., T.Y., S.M., K.Y., A.T.), Sanriku, Iwate 022-0101, Japan; Department of Biochemistry and Molecular Biology, University of New Hampshire (S.A.S.), Durham, New Hampshire 03824; Sado Marine Biological Station, Faculty of Science, Niigata University (N.M.), Sado, Niigata 952-2135, Japan; and Division of Life Sciences, University of Toronto at Scarborough (J.Y.), Toronto, Ontario, Canada M1C 1A4
Address all correspondence and requests for reprints to: Hiroshi Kawauchi, Ph.D., Laboratory of Molecular Endocrinology, School of Fisheries Sciences, Kitasato University, Sanriku, Iwate 0220101, Japan. E-mail: hiroshi{at}kitasato-u.ac.jp.
GH was identified in the sea lamprey, an extant representative of a group of the most ancient vertebrates, the Agnatha. A putative GH-cDNA was cloned from the pituitary by RT-PCR. The entire coding region comprised an open-reading frame of 203 amino acids (aa). The mature protein was also isolated from pituitaries, and fractionated by gel filtration and reverse-phase HPLC. A putative GH was monitored by Western blotting with a rabbit antiserum against a synthetic peptide corresponding to pre-GH sequence (aa 2945). Sequence analysis of the purified protein demonstrated that the prehormone consists of a signal peptide of 22 aa and the mature protein of 181 aa, which shows 25% sequence identity with sturgeon GH. The site of production was identified through immunohistochemistry to be cells of the dorsal half of the proximal pars distalis of the pituitary. Following cDNA cloning of lamprey IGF cDNA, it was shown using RT-PCR that lamprey GH stimulates IGF expression in lamprey liver. This is the first study in which a member of the GH/prolactin/somatolactin family has been identified in an agnathan. In addition, GH appears to be the only member of this hormone family in the sea lamprey. Evidence suggests that GH is the ancestral hormone in the molecular evolution of the GH family and that the endocrine mechanism for growth stimulation was established at an early stage of vertebrate evolution.
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