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Thyrotrophin in the pars tuberalis triggers photoperiodic response

Abstract

Molecular mechanisms regulating animal seasonal breeding in response to changing photoperiod are not well understood. Rapid induction of gene expression of thyroid-hormone-activating enzyme (type 2 deiodinase, DIO2) in the mediobasal hypothalamus (MBH) of the Japanese quail (Coturnix japonica) is the earliest event yet recorded in the photoperiodic signal transduction pathway. Here we show cascades of gene expression in the quail MBH associated with the initiation of photoinduced secretion of luteinizing hormone. We identified two waves of gene expression. The first was initiated about 14 h after dawn of the first long day and included increased thyrotrophin (TSH) β-subunit expression in the pars tuberalis; the second occurred approximately 4 h later and included increased expression of DIO2. Intracerebroventricular (ICV) administration of TSH to short-day quail stimulated gonadal growth and expression of DIO2 which was shown to be mediated through a TSH receptor–cyclic AMP (cAMP) signalling pathway. Increased TSH in the pars tuberalis therefore seems to trigger long-day photoinduced seasonal breeding.

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Figure 1: Plasma luteinizing hormone and genome-wide analysis of genes expressed in the quail MBH during the first day of photostimulation (time 0 h is dawn of the first long day).
Figure 2: Localization of TSH-β and TSHR in the pars tuberalis and MBH.
Figure 3: Induction of the expression of DIO2 and three other second-wave genes by ICV injection of TSH and inhibition by ICV injection of anti-TSH-β IgG.
Figure 5: Effect of chronic ICV infusion of TSH on MBH DIO2 expression and testicular growth under short-day conditions.
Figure 4: Involvement of a cAMP signalling pathway in TSH induction of DIO2 gene expression.

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Gene Expression Omnibus

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Acknowledgements

We thank T. Kondo and the Nagoya University Radioisotope Centre for use of facilities. We also thank J. A. Proudman and A. F. Parlow for providing the chicken luteinizing hormone radioimmunoassay kit and the bovine TSH, respectively. This work was done as a part of the Program for Promotion of Basic Research Activities for Innovative Biosciences (PROBRAIN) and, in part, by Grant-in-Aid for Scientific Research (S), (B), Grant-in-Aid for Young Scientists (S), Grant-in-Aid for JSPS Fellows from the Japanese Society for the Promotion of Science, and a grant of the Genome Network Project from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Author Contributions T.Yo. conceived and directed the work. N.N., H.O., T.Ya., T.A., T.T., K.H., S.Y., Y.K., S.K., Y.U. and T.Yo. performed the microarray analysis and in situ hybridization. N.N., T.K., H.R.U. and T.Yo. analysed the microarray data. N.N. performed the quantitative PCR and promoter assay. M.I. and P.J.S. determined the luteinizing hormone assay. H.O. and M.I. performed the 125I-labelled TSH binding assay. T.Ya. and A.I. performed the immunocytochemistry. T.Ya., T.A. and A.I. examined the ICV injection and infusion. N.N., H.O., Y.S. and S.S. determined transcriptional start sites and genomic DNA sequences. T.Ni. cloned EYA, SIX and DACH family. M.M., T.Na. and S.E. provided laboratory facilities and new materials. All authors discussed the results and commented on the manuscript. T.Yo. and P.J.S. wrote the paper.

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Correspondence to Takashi Yoshimura.

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The microarray data and DNA sequence information have been deposited in NCBI Gene Expression Omnibus (GEO) (GSE8016, GSE8017, GSE8018) and DDBJ/EMBL/GenBank (AB307676, AB307677, AB307678, AB307679, AB307680, AB307681 ), respectively.

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Nakao, N., Ono, H., Yamamura, T. et al. Thyrotrophin in the pars tuberalis triggers photoperiodic response. Nature 452, 317–322 (2008). https://doi.org/10.1038/nature06738

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