@article{MTMT:2922923,
	title = {Differences in hypothalamic type 2 deiodinase ubiquitination explain localized sensitivity to thyroxine.},
	url = {https://m2.mtmt.hu/api/publication/2922923},
	author = {Werneck, de Castro JP and Fonseca, TL and Ueta, CB and McAninch, EA and Abdalla, S and Wittmann, Gábor and Lechan, RM and Gereben, Balázs and Bianco, AC},
	doi = {10.1172/JCI77588},
	journal-iso = {J CLIN INVEST},
	journal = {JOURNAL OF CLINICAL INVESTIGATION},
	volume = {125},
	unique-id = {2922923},
	issn = {0021-9738},
	abstract = {The current treatment for patients with hypothyroidism is levothyroxine (L-T4) along with normalization of serum thyroid-stimulating hormone (TSH). However, normalization of serum TSH with L-T4 monotherapy results in relatively low serum 3,5,3'-triiodothyronine (T3) and high serum thyroxine/T3 (T4/T3) ratio. In the hypothalamus-pituitary dyad as well as the rest of the brain, the majority of T3 present is generated locally by T4 deiodination via the type 2 deiodinase (D2); this pathway is self-limited by ubiquitination of D2 by the ubiquitin ligase WSB-1. Here, we determined that tissue-specific differences in D2 ubiquitination account for the high T4/T3 serum ratio in adult thyroidectomized (Tx) rats chronically implanted with subcutaneous L-T4 pellets. While L-T4 administration decreased whole-body D2-dependent T4 conversion to T3, D2 activity in the hypothalamus was only minimally affected by L-T4. In vivo studies in mice harboring an astrocyte-specific Wsb1 deletion as well as in vitro analysis of D2 ubiquitination driven by different tissue extracts indicated that D2 ubiquitination in the hypothalamus is relatively less. As a result, in contrast to other D2-expressing tissues, the hypothalamus is wired to have increased sensitivity to T4. These studies reveal that tissue-specific differences in D2 ubiquitination are an inherent property of the TRH/TSH feedback mechanism and indicate that only constant delivery of L-T4 and L-T3 fully normalizes T3-dependent metabolic markers and gene expression profiles in Tx rats.},
	keywords = {Animals; Humans; MICE; RATS; Ubiquitination/*physiology; Mice, Knockout; Gene Deletion; Iodide Peroxidase/genetics/*metabolism; Gene Expression Regulation, Enzymologic/*physiology; Ubiquitin-Protein Ligases/genetics/metabolism; Thyroxine/genetics/*metabolism/pharmacology; Thyrotropin/genetics/metabolism; Hypothyroidism/drug therapy/enzymology/genetics/pathology; Hypothalamo-Hypophyseal System/*enzymology},
	year = {2015},
	eissn = {1558-8238},
	pages = {769-781}
}

@article{MTMT:2194586,
	title = {Coordination of hypothalamic and pituitary T3 production regulates TSH expression},
	url = {https://m2.mtmt.hu/api/publication/2194586},
	author = {Fonseca, TL and Medina, MC and Campos, MPO and Wittmann, Gábor and Werneck-de-Castro, JP and Arrojo, e Drigo Rafael and Mora-Garzon, ME and Ueta, CB and Caicedo, A and Fekete, Csaba and Gereben, Balázs and Lechan, RM and Bianco, AC},
	doi = {10.1172/JCI61231},
	journal-iso = {J CLIN INVEST},
	journal = {JOURNAL OF CLINICAL INVESTIGATION},
	volume = {123},
	unique-id = {2194586},
	issn = {0021-9738},
	year = {2013},
	eissn = {1558-8238},
	pages = {1492-1500}
}

@article{MTMT:109956,
	title = {Cellular and Molecular Basis of Deiodinase-Regulated Thyroid Hormone Signaling},
	url = {https://m2.mtmt.hu/api/publication/109956},
	author = {Gereben, Balázs and Zavacki, AM and Ribich, S and Kim, BW and Huang, SA and Simonides, WS and Zeöld, Anikó and Bianco, AC},
	doi = {10.1210/er.2008-0019},
	journal-iso = {ENDOCR REV},
	journal = {ENDOCRINE REVIEWS},
	volume = {29},
	unique-id = {109956},
	issn = {0163-769X},
	abstract = {The iodothyronine deiodinases initiate or terminate thyroid hormone action, and therefore are critical for the biological effects mediated by thyroid hormone. Over the years research has focused on their role in preserving serum levels of the biologically active molecule triiodothyronine (T3) during iodine deficiency. More recently, a fascinating new role of these enzymes has been unveiled. The activating deiodinase (D2) and the inactivating deiodinase (D3) can locally increase or decrease thyroid hormone signaling in a tissue- and temporal-specific fashion, independently of changes in thyroid hormone serum concentrations. This mechanism is particularly relevant as deiodinase expression can be modulated by a wide variety of endogenous signaling molecules such as sonic hedgehog, NF-kappaB, growth factors, bile acids, HIF-1alpha, as well as a growing number of xenobiotic substances. In light of these findings, it seems clear that deiodinases play a much broader role than once thought, with great ramifications for the control of thyroid hormone signaling during vertebrate development and metamorphosis, as well as injury response, tissue repair, hypothalamic function, and energy homeostasis in adults.},
	year = {2008},
	eissn = {1945-7189},
	pages = {898-938}
}

@article{MTMT:109768,
	title = {Metabolic instability of type 2 deiodinase is transferable to stable proteins independently of subcellular localization},
	url = {https://m2.mtmt.hu/api/publication/109768},
	author = {Zeöld, Anikó and Pormuller, L and Dentice, M and Harney, JW and Curcio, Morelli C and Tente, SM and Bianco, AC and Gereben, Balázs},
	doi = {10.1074/jbc.M604728200},
	journal-iso = {J BIOL CHEM},
	journal = {JOURNAL OF BIOLOGICAL CHEMISTRY},
	volume = {281},
	unique-id = {109768},
	issn = {0021-9258},
	year = {2006},
	eissn = {1083-351X},
	pages = {31538-31543}
}

@article{MTMT:109594,
	title = {The Hedgehog-inducible ubiquitin ligase subunit WSB-1 modulates thyroid hormone activation and PTHrP secretion in the developing growth plate},
	url = {https://m2.mtmt.hu/api/publication/109594},
	author = {Dentice, M and Bandyopadhyay, A and Gereben, Balázs and Callebaut, I and Christoffolete, MA and Kim, BW and Nissim, S and Mornon, JP and Zavacki, AM and Zeöld, Anikó and Capelo, LP and Curcio, Morelli C and Ribeiro, R and Harney, JW and Tabin, CJ and Bianco, AC},
	doi = {10.1038/ncb1272},
	journal-iso = {NAT CELL BIOL},
	journal = {NATURE CELL BIOLOGY},
	volume = {7},
	unique-id = {109594},
	issn = {1465-7392},
	year = {2005},
	eissn = {1476-4679},
	pages = {698-705}
}

@article{MTMT:109451,
	title = {Chronic cardiac-specific thyrotoxicosis increases myocardial β adrenergic responsiveness},
	url = {https://m2.mtmt.hu/api/publication/109451},
	author = {Carvalho, Bianco SD and Kim, BW and Zhang, JX and Harney, JW and Ribeiro, RS and Gereben, Balázs and Bianco, AC and Mende, U and Larsen, PR},
	doi = {10.1210/me.2003-0125},
	journal-iso = {MOL ENDOCRINOL},
	journal = {MOLECULAR ENDOCRINOLOGY},
	volume = {18},
	unique-id = {109451},
	issn = {0888-8809},
	year = {2004},
	eissn = {1944-9917},
	pages = {1840-1849}
}

@article{MTMT:109174,
	title = {Biochemistry, cellular and molecular biology, and physiological roles of the iodothyronine selenodeiodinases},
	url = {https://m2.mtmt.hu/api/publication/109174},
	author = {Bianco, AC and Salvatore, D and Gereben, Balázs and Berry, MJ and Larsen, PR},
	doi = {10.1210/er.23.1.38},
	journal-iso = {ENDOCR REV},
	journal = {ENDOCRINE REVIEWS},
	volume = {23},
	unique-id = {109174},
	issn = {0163-769X},
	year = {2002},
	eissn = {1945-7189},
	pages = {38-89}
}

@article{MTMT:1802122,
	title = {Serum interleukin-6 and bone metabolism in patients with thyroid function disorders},
	url = {https://m2.mtmt.hu/api/publication/1802122},
	author = {Lakatos, Péter and Földes, János and Horváth, Csaba and Kiss, L and Tatrai, A and Takács, István and Tarjan, G and Stern, P H},
	doi = {10.1210/jcem.82.1.3641},
	journal-iso = {J CLIN ENDOCR METAB},
	journal = {JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM},
	volume = {82},
	unique-id = {1802122},
	issn = {0021-972X},
	abstract = {To determine the possible involvement of interleukin-6(IL-6) in the bone loss of hyperthyroidism, relationships between thyroid status, biochemical and densitometric parameters of bone metabolism, and IL-6 were studied in female subjects. Patients with hyperthyroidism caused by either toxic nodular goiter or Graves' disease had significantly higher serum IL-6 concentrations than normal controls. Within the control group, serum IL-6 was higher in postmenopausal than in premenopausal women, but this influence of menopausal status was not seen in the hyperthyroid patients. The production of IL-6 by blood mononuclear cells was higher in cells from the hyperthyroid women. Bone turnover was increased in the hyperthyroid patients based on serum osteocalcin and urinary deoxypyridinoline excretion, and the hyperthyroid group also had reduced radius bone mineral content (BMC). A subgroup of hyperthyroid patients who had the lowest BMC (values more than 1 SD below normal age-matched controls) also had serum IL-6 concentrations significantly greater than those of hyperthyroid patients showing less reduction of BMC. The correlations observed in this study support the possibility that IL-6 plays a role in mediating the bone loss that results from excess thyroid hormone.},
	keywords = {Aged; Adult; Female; Middle Aged; Humans; ARTICLE; human; priority journal; clinical article; Bone Density; Bone metabolism; Bone and Bones; protein blood level; interleukin 6; hyperthyroidism; Leukocytes, Mononuclear; immunopathogenesis; amino acids; Graves disease; Interleukin-6; bone mineralization; bone atrophy; osteocalcin; Postmenopause; premenopause; Goiter, Nodular},
	year = {1997},
	eissn = {1945-7197},
	pages = {78-81},
	orcid-numbers = {Lakatos, Péter/0000-0002-7652-3671; Horváth, Csaba/0000-0002-0490-7932; Takács, István/0000-0002-7810-4833}
}

@article{MTMT:1802374,
	title = {Thyroid hormones increase insulin-like growth factor I content in the medium of rat bone tissue},
	url = {https://m2.mtmt.hu/api/publication/1802374},
	author = {Lakatos, Péter and Caplice, M D and Khanna, V and Stern, P H},
	doi = {10.1002/jbmr.5650081210},
	journal-iso = {J BONE MINER RES},
	journal = {JOURNAL OF BONE AND MINERAL RESEARCH},
	volume = {8},
	unique-id = {1802374},
	issn = {0884-0431},
	abstract = {The mechanism of action of thyroid hormones on bone is still not clear. At low concentrations, they stimulate bone formation; at high concentrations, they elicit bone resorption in vitro and in vivo. In the present study we investigated the effect of T3 and T4 as well as their active and inactive analogs (TRIAC, SKF L-94901, rT3, and DIT) on the IGF-I and TNF-α content in the medium of UMR-106 rat osteoblastic cells and fetal rat limb bones. In the dose-response studies, a biphasic increase in medium IGF-I was observed in both cells and limb bones, with peak stimulatory concentrations of 10-8 M for T3 and 10-7 M for T4 in both systems. At higher concentrations, at which thyroid hormones elicit bone resorption, the stimulatory effect diminished and finally was no longer detectable. The active analogs TRIAC and SKF L-94901 also enhanced IGF-I release in UMR-106 cells. The inactive compounds rT3 and DIT failed to increase IGF-I in these cultures. The protein content of the cell culture wells exposed to high concentrations of thyroid hormones was similar to those containing low concentrations, indicating that the decrease in IGF-I content at high doses was not due to toxic effects. This was also confirmed by trypan blue exclusion. Time course studies with UMR-106 cells revealed a significant increase in medium IGF-I after 2 days of incubation. No significant further increase was observed after this up to 5 days of culture. In contrast, the medium of limb bone cultures showed a linear increase in IGF-I content up to 7 days of culture. No TNF-α production was observed in either UMR-106 cells or fetal limb bones. Also, no increase in medium TNF-α levels was seen in response to thyroid hormones. Based on our results, we conclude that IGF-I may be responsible for some of the anabolic effects of thyroid hormones in bone tissue, but TNF-α, at least in the models we used, does not play a role in the mediation of thyroid hormone action.},
	keywords = {PROTEIN; RATS; ARTICLE; tumor necrosis factor alpha; animal; Rats, Sprague-Dawley; Dose-Response Relationship, Drug; nonhuman; animal tissue; animal cell; Tumor Cells, Cultured; Bone metabolism; fetus; Bone and Bones; Insulin-Like Growth Factor I; somatomedin C; liothyronine; Tissue Culture; Culture Media; Tumor Necrosis Factor; Support, U.S. Gov't, P.H.S.; Extremities; Bone Resorption; osteolysis; thyroxine; ossification; bone tissue; protein content; Triiodothyronine; Osteoblasts; osteoblast; Osteosarcoma; thyroid hormones; Thyronines; Triiodothyronine, Reverse; 3,3',5' triiodothyronine; tiratricol; diiodotyrosine; 3,5 dibromo 3' (2,3 dihydro 3 oxo 6 pyridazinylmethyl)thyronine; rat},
	year = {1993},
	eissn = {1523-4681},
	pages = {1475-1481},
	orcid-numbers = {Lakatos, Péter/0000-0002-7652-3671}
}

@article{MTMT:1802377,
	title = {Effects of cyclosporins and transforming growth factor β1 on thyroid hormone action in cultured fetal rat limb bones},
	url = {https://m2.mtmt.hu/api/publication/1802377},
	author = {Lakatos, Péter and Stern, P H},
	doi = {10.1007/BF00298788},
	journal-iso = {CALCIFIED TISSUE INT},
	journal = {CALCIFIED TISSUE INTERNATIONAL},
	volume = {50},
	unique-id = {1802377},
	issn = {0171-967X},
	abstract = {To study the mechanism of action of thyroid hormones on bone, we examined the effects of immunosuppressive and nonimmunosuppressive cyclosporins, as well as of transforming growth factor β1 (TGFβ1), 17β-estradiol (E2), and dihydroxytestosterone (DHT) on thyroxine (T4)- and triiodothyronine (T3)-stimulated bone resorption in fetal rat limb bones. The immunosuppressive cyclosporins A (CsA) and G (CsG) inhibited thyroid hormone (T4 + T3)-stimulated resorption and β-glucuronidase release into the culture medium, whereas the weak or nonimmunosuppressive cyclosporins D (CsD) and H (CsH) did not show this effect. Increasing the medium calcium concentration reduced the ability of T4 to stimulate 45Ca release, while not significantly affecting the response to CsA. TGFβ1 elicited a biphasic effect when administered together with T4. During the first 3 days of culture, TGFβ1 elicited a small, nonsignificant decrease in released 45Ca; during a subsequent 3 days of culture, it enhanced T4-stimulated bone resorption significantly. These effects differed from those of TGFβ1 on parathormone-stimulated resorption. E2 and DHT did not influence the action of T4 on bone tissue. These results suggest that the mechanism of action of thyroid hormones on bone may involve immune factors, as well.},
	keywords = {calcium; RATS; ARTICLE; CYCLOSPORINS; ESTRADIOL; animal; priority journal; controlled study; Dose-Response Relationship, Drug; Rats, Inbred Strains; nonhuman; animal tissue; fetus; embryo; Bone and Bones; liothyronine; Tissue Culture; Support, U.S. Gov't, P.H.S.; drug mechanism; cyclosporin A; cyclosporin; immunosuppressive treatment; Extremities; Transforming Growth Factor beta1; transforming growth factor beta; Bone Resorption; osteolysis; enzyme release; thyroxine; calcium transport; hormone action; Glucuronidase; organ culture; Parathyroid Hormone; thyroid hormones; Thyroid hormone; LIMB; Hydroxytestosterones; testosterone derivative; cyclosporin h; cyclosporin g; cyclosporin d; TGFβ1; rat},
	year = {1992},
	eissn = {1432-0827},
	pages = {123-128},
	orcid-numbers = {Lakatos, Péter/0000-0002-7652-3671}
}

@article{MTMT:1802379,
	title = {Evidence for direct non-genomic effects of triiodothyronine on bone rudiments in rats: Stimulation of the inositol phosphate second messenger system},
	url = {https://m2.mtmt.hu/api/publication/1802379},
	author = {Lakatos, Péter and Stern, P H},
	doi = {10.1530/acta.0.1250603},
	journal-iso = {ACTA ENDOCRINOL},
	journal = {ACTA ENDOCRINOLOGICA},
	volume = {125},
	unique-id = {1802379},
	issn = {0001-5598},
	abstract = {Thyroid hormones increase cytosolic free calcium by binding to plasma membrane receptors in several tissues. This calcium increase appears to initiate extranuclear effects in these tissues. Increases in cytosolic calcium are often a consequence of stimulation of inositol phosphate second messenger pathway. Several calcemic hormones act via this signal transduction route. Therefore we investigated the effects of the metabolically active T3 and the inactive analogues 3,5-diiodotyrosine and rT3 on the inositol phosphate pathway in fetal rat limb bone cultures prelabeled with [3H]myoinositol. Labelled inositol and inositol phosphates were separated by HPLC. There was a significant increase in the radioactivity in inositol bis- and trisphosphates after 1 min of exposure to 10-7 mol/l T3. Stimulation was also observed at 10-6 mol/l T3, but not at 10-5 mol/l. Time course studies demonstrated a rapid effect of T3 on inositol phosphates within 30 seconds that lasted through 5 min. After 20 min incubation with T3, no increase was observed in inositol mono- and bisphoshates, and a decrease was seen in inositol trisphosphate. Pretreatment with indomethacin prevented these effects of T3. 3,5-diiodothyrosine and rT3 did not affect inositol phosphate metabolism. These results suggest the existence of plasma membrane-associated receptors for T3 in bone, in addition to the nuclear receptors demonstrated previously. The role of these receptors in the effects of thyroid hormones on bone remains to be established.},
	keywords = {Female; RATS; ARTICLE; signal transduction; INOSITOL; animal; Chromatography, High Pressure Liquid; priority journal; Dose-Response Relationship, Drug; Time Factors; Rats, Inbred Strains; nonhuman; animal tissue; animal cell; Cells, Cultured; Bone; pregnancy; fetus; Bone and Bones; liothyronine; cell culture; Tritium; Support, U.S. Gov't, P.H.S.; Indomethacin; indometacin; thyroid gland; Triiodothyronine; membrane receptor; phosphoinositide metabolism; inositol trisphosphate; Second Messenger Systems; cell nucleus receptor; 3,3',5' triiodothyronine; bone cell; inositol phosphate; diiodothyronine; Inositol Phosphates; diiodotyrosine; rat},
	year = {1991},
	pages = {603-608},
	orcid-numbers = {Lakatos, Péter/0000-0002-7652-3671}
}