title: Increased Thyroid Hormone Activation Accompanies the Formation of Thyroid Hormone-Dependent Negative Feedback in Developing Chicken Hypothalamus.
abstract: The hypothalamic-pituitary-thyroid axis is governed by hypophysiotropic TRH-synthesizing neurons located in the hypothalamic paraventricular nucleus under control of the negative feedback of thyroid hormones. The mechanisms underlying the ontogeny of this phenomenon are poorly understood. We aimed to determine the onset of thyroid hormone-mediated hypothalamic-negative feedback and studied how local hypothalamic metabolism of thyroid hormones could contribute to this process in developing chicken. In situ hybridization revealed that whereas exogenous T4 did not induce a statistically significant inhibition of TRH expression in the paraventricular nucleus at embryonic day (E)19, T4 treatment was effective at 2 days after hatching (P2). In contrast, TRH expression responded to T3 treatment in both age groups. TSHβ mRNA expression in the pituitary responded to T4 in a similar age-dependent manner. Type 2 deiodinase (D2) was expressed from E13 in tanycytes of the mediobasal hypothalamus, and its activity increased between E15 and P2 both in the mediobasal hypothalamus and in tanycyte-lacking hypothalamic regions. Nkx2.1 was coexpressed with D2 in E13 and P2 tanycytes and transcription of the cdio2 gene responded to Nkx2.1 in U87 glioma cells, indicating its potential role in the developmental regulation of D2 activity. The T3-degrading D3 enzyme was also detected in tanycytes, but its level was not markedly changed before and after the period of negative feedback acquisition. These findings suggest that increasing the D2-mediated T3 generation during E18-P2 could provide the sufficient local T3 concentration required for the onset of T3-dependent negative feedback in the developing chicken hypothalamus.
authors.affiliation: Department of Endocrine Neurobiology (P.M., T.F., M.D., A.S.S., É.H., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083 Budapest, Hungary; János Szentágothai PhD School of Neurosciences (P.M., A.S.S.), Semmelweis University, H-1085 Budapest, Hungary; Laboratory of Comparative Endocrinology (P.V., V.M.D.), Department of Biology, Division of Animal Physiology and Neurobiology, KU Leuven, B-3001 Leuven, Belgium; and Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111.
authors.forename: P
authors.initials: P
authors.lastname: Mohácsik
authors.affiliation: Department of Endocrine Neurobiology (P.M., T.F., M.D., A.S.S., É.H., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083 Budapest, Hungary; János Szentágothai PhD School of Neurosciences (P.M., A.S.S.), Semmelweis University, H-1085 Budapest, Hungary; Laboratory of Comparative Endocrinology (P.V., V.M.D.), Department of Biology, Division of Animal Physiology and Neurobiology, KU Leuven, B-3001 Leuven, Belgium; and Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111.
authors.forename: T
authors.initials: T
authors.lastname: Füzesi
authors.affiliation: Department of Endocrine Neurobiology (P.M., T.F., M.D., A.S.S., É.H., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083 Budapest, Hungary; János Szentágothai PhD School of Neurosciences (P.M., A.S.S.), Semmelweis University, H-1085 Budapest, Hungary; Laboratory of Comparative Endocrinology (P.V., V.M.D.), Department of Biology, Division of Animal Physiology and Neurobiology, KU Leuven, B-3001 Leuven, Belgium; and Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111.
authors.forename: M
authors.initials: M
authors.lastname: Doleschall
authors.affiliation: Department of Endocrine Neurobiology (P.M., T.F., M.D., A.S.S., É.H., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083 Budapest, Hungary; János Szentágothai PhD School of Neurosciences (P.M., A.S.S.), Semmelweis University, H-1085 Budapest, Hungary; Laboratory of Comparative Endocrinology (P.V., V.M.D.), Department of Biology, Division of Animal Physiology and Neurobiology, KU Leuven, B-3001 Leuven, Belgium; and Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111.
authors.forename: A
authors.initials: A
authors.lastname: Szilvásy-Szabó
authors.affiliation: Department of Endocrine Neurobiology (P.M., T.F., M.D., A.S.S., É.H., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083 Budapest, Hungary; János Szentágothai PhD School of Neurosciences (P.M., A.S.S.), Semmelweis University, H-1085 Budapest, Hungary; Laboratory of Comparative Endocrinology (P.V., V.M.D.), Department of Biology, Division of Animal Physiology and Neurobiology, KU Leuven, B-3001 Leuven, Belgium; and Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111.
authors.forename: P
authors.initials: P
authors.lastname: Vancamp
authors.affiliation: Department of Endocrine Neurobiology (P.M., T.F., M.D., A.S.S., É.H., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083 Budapest, Hungary; János Szentágothai PhD School of Neurosciences (P.M., A.S.S.), Semmelweis University, H-1085 Budapest, Hungary; Laboratory of Comparative Endocrinology (P.V., V.M.D.), Department of Biology, Division of Animal Physiology and Neurobiology, KU Leuven, B-3001 Leuven, Belgium; and Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111.
authors.forename: É
authors.initials: É
authors.lastname: Hadadi
authors.affiliation: Department of Endocrine Neurobiology (P.M., T.F., M.D., A.S.S., É.H., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083 Budapest, Hungary; János Szentágothai PhD School of Neurosciences (P.M., A.S.S.), Semmelweis University, H-1085 Budapest, Hungary; Laboratory of Comparative Endocrinology (P.V., V.M.D.), Department of Biology, Division of Animal Physiology and Neurobiology, KU Leuven, B-3001 Leuven, Belgium; and Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111.
authors.forename: V M
authors.initials: VM
authors.lastname: Darras
authors.affiliation: Department of Endocrine Neurobiology (P.M., T.F., M.D., A.S.S., É.H., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083 Budapest, Hungary; János Szentágothai PhD School of Neurosciences (P.M., A.S.S.), Semmelweis University, H-1085 Budapest, Hungary; Laboratory of Comparative Endocrinology (P.V., V.M.D.), Department of Biology, Division of Animal Physiology and Neurobiology, KU Leuven, B-3001 Leuven, Belgium; and Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111.
authors.forename: C
authors.initials: C
authors.lastname: Fekete
authors.affiliation: Department of Endocrine Neurobiology (P.M., T.F., M.D., A.S.S., É.H., C.F., B.G.), Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083 Budapest, Hungary; János Szentágothai PhD School of Neurosciences (P.M., A.S.S.), Semmelweis University, H-1085 Budapest, Hungary; Laboratory of Comparative Endocrinology (P.V., V.M.D.), Department of Biology, Division of Animal Physiology and Neurobiology, KU Leuven, B-3001 Leuven, Belgium; and Department of Medicine (C.F.), Division of Endocrinology, Diabetes, and Metabolism, Tupper Research Institute, Tufts Medical Center, Boston, Massachusetts 02111.
authors.forename: B
authors.initials: B
authors.lastname: Gereben
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D045744:Cell Line, Tumor; D002642:Chick Embryo; D063928:Ependymoglial Cells / Q000187:drug effects / Q000378:metabolism; D025461:Feedback, Physiological / Q000187:drug effects / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000196:embryology / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007453:Iodide Peroxidase / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009687:Nuclear Proteins / Q000187:drug effects / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013961:Thyroid Gland / Q000378:metabolism*; D000074482:Thyroid Nuclear Factor 1; D037322:Thyrotropin, beta Subunit / Q000235:genetics; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*; D013974:Thyroxine / Q000378:metabolism* / Q000494:pharmacology; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism; D014284:Triiodothyronine / Q000187:drug effects / Q000378:metabolism; D000097564:Iodothyronine Deiodinase Type II
chemical_list: D007453:Iodide Peroxidase; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000074482:Thyroid Nuclear Factor 1; D037322:Thyrotropin, beta Subunit; D013973:Thyrotropin-Releasing Hormone; D013974:Thyroxine; D014157:Transcription Factors; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II; C117274:iodothyronine deiodinase type III