PMID- 24907629 OWN - NLM STAT- MEDLINE DCOM- 20150423 LR - 20181202 IS - 1095-6840 (Electronic) IS - 0016-6480 (Linking) VI - 204 DP - 2014 Aug 1 TI - Thyroid hormone and retinoid X receptor function and expression during sea lamprey (Petromyzon marinus) metamorphosis. PG - 211-22 LID - S0016-6480(14)00230-5 [pii] LID - 10.1016/j.ygcen.2014.05.030 [doi] AB - Sea lampreys (Petromyzon marinus) are members of the ancient class Agnatha and undergo a metamorphosis that transforms blind, sedentary, filter-feeding larvae into free-swimming, parasitic juveniles. Thyroid hormones (THs) appear to be important for lamprey metamorphosis, however, serum TH concentrations are elevated in the larval phase, decline rapidly during early metamorphosis and remain low until metamorphosis is complete; these TH fluctuations are contrary to those of other metamorphosing vertebrates. Moreover, thyroid hormone synthesis inhibitors (goitrogens) induce precocious metamorphosis and exogenous TH treatments disrupt natural metamorphosis in P. marinus. Given that THs exert their effects by binding to TH nuclear receptors (TRs) that often act as heterodimers with retinoid X receptors (RXRs), we cloned and characterized these receptors from P. marinus and examined their expression during metamorphosis. Two TRs (PmTR1 and PmTR2) and three RXRs (PmRXRs) were isolated from P. marinus cDNA. Phylogenetic analyses group the PmTRs together on a branch prior to the gnathostome TRalpha/beta split. The three RXRs also group together, but our data indicated that these transcripts are most likely either allelic variants of the same gene locus, or the products of a lamprey-specific duplication event. Importantly, these P. marinus receptors more closely resemble vertebrate as opposed to invertebrate chordate receptors. Functional analysis revealed that PmTR1 and PmTR2 can activate transcription of TH-responsive genes when treated with nanomolar concentrations of TH and they have distinct pharmacological profiles reminiscent of vertebrate TRbeta and TRalpha, respectively. Also similar to other metamorphosing vertebrates, expression patterns of the PmTRs during lamprey metamorphosis suggest that PmTR1 has a dynamic, tissue-specific expression pattern that correlates with tissue morphogenesis and biochemical changes and PmTR2 has a more uniform expression pattern. This TR expression data suggests that THs, either directly or via a metabolite, may function to positively modulate changes at the tissue or organ levels during lamprey metamorphosis. Collectively the results presented herein support the hypothesis that THs have a dual functional role in the lamprey life cycle whereby high levels promote larval feeding, growth and lipogenesis and low levels promote metamorphosis. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Manzon, Lori A AU - Manzon LA AD - Department of Zoology and Division of Life Sciences, University of Toronto, Toronto, ON M1A 1C4, Canada. FAU - Youson, John H AU - Youson JH AD - Department of Zoology and Division of Life Sciences, University of Toronto, Toronto, ON M1A 1C4, Canada. FAU - Holzer, Guillaume AU - Holzer G AD - Institut de Genomique Fonctionnelle de Lyon, Universite de Lyon, Universite Lyon 1, CNRS, Ecole Normale Superieure de Lyon, 46 allee d'Italie, 69364 Lyon Cedex 07, France. FAU - Staiano, Leopoldo AU - Staiano L AD - Cellular and Developmental Laboratory, Stazione Zoologica Anton Dohrn, Villa Comunale, 80121 Napoli, Italy. FAU - Laudet, Vincent AU - Laudet V AD - Institut de Genomique Fonctionnelle de Lyon, Universite de Lyon, Universite Lyon 1, CNRS, Ecole Normale Superieure de Lyon, 46 allee d'Italie, 69364 Lyon Cedex 07, France. FAU - Manzon, Richard G AU - Manzon RG AD - Department of Biology, University of Regina, 3737 Wascana Parkway, Regina, SK S4S 0A2, Canada. Electronic address: richard.manzon@uregina.ca. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140604 PL - United States TA - Gen Comp Endocrinol JT - General and comparative endocrinology JID - 0370735 RN - 0 (RNA, Messenger) RN - 0 (Retinoid X Receptors) RN - 0 (Thyroid Hormone Receptors alpha) RN - 0 (Thyroid Hormone Receptors beta) SB - IM MH - Amino Acid Sequence MH - Animals MH - Blotting, Northern MH - Cloning, Molecular MH - *Gene Expression Regulation, Developmental MH - Larva/metabolism MH - Metamorphosis, Biological/*physiology MH - Molecular Sequence Data MH - Petromyzon/*physiology MH - Phylogeny MH - RNA, Messenger/genetics MH - Real-Time Polymerase Chain Reaction MH - Retinoid X Receptors/genetics/*metabolism MH - Reverse Transcriptase Polymerase Chain Reaction MH - Sequence Homology, Amino Acid MH - Thyroid Hormone Receptors alpha/genetics/*metabolism MH - Thyroid Hormone Receptors beta/genetics/*metabolism OTO - NOTNLM OT - Lamprey OT - Metamorphosis OT - Phylogenetic analyses OT - Retinoid X receptors OT - Thyroid hormone nuclear receptors EDAT- 2014/06/08 06:00 MHDA- 2015/04/24 06:00 CRDT- 2014/06/08 06:00 PHST- 2014/03/28 00:00 [received] PHST- 2014/05/16 00:00 [revised] PHST- 2014/05/20 00:00 [accepted] PHST- 2014/06/08 06:00 [entrez] PHST- 2014/06/08 06:00 [pubmed] PHST- 2015/04/24 06:00 [medline] AID - S0016-6480(14)00230-5 [pii] AID - 10.1016/j.ygcen.2014.05.030 [doi] PST - ppublish SO - Gen Comp Endocrinol. 2014 Aug 1;204:211-22. doi: 10.1016/j.ygcen.2014.05.030. Epub 2014 Jun 4.