Review
Biochemistry & Molecular Biology
Andrea Alcaide Martin, Steffen Mayerl
Summary: Proper brain development relies on timely availability of thyroid hormone (TH), which requires regulated expression of TH signaling components. Abnormal TH levels and mutations in TH signaling components can have detrimental effects on brain development and neurological functions. The involvement of TH signaling in the development of different neurotransmitter systems has gained attention. This review summarizes the regulation of TH signaling components during brain development and discusses how altered TH signaling compromises the development of specific neuron types.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Josef Koehrle, Caroline Fraedrich
Summary: Iodothyronine deiodinases (DIO) are a family of selenoproteins that play a crucial role in controlling the availability of thyroid hormones. DIO1 and DIO2 activate the prohormone T4 to the active form T3, while DIO3 inactivates both T4 and T3. DIOs are regulated by various factors and exhibit species-specific expression patterns. Selenium status has a modest impact on DIO expression, and DIO function is impaired during severe selenium deficiency. DIO variants and mutations have been identified, and efforts are underway to develop selective drugs targeting DIO. This review focuses on the biochemical characteristics and importance of DIOs in the production of active hormone T3, as well as the impact of nutritional, pharmacological, and environmental factors on DIO function.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Endocrinology & Metabolism
Chen-Kai Chou, Shun-Yu Chi, Yi-Yung Hung, Yi-Chien Yang, Hung-Chun Fu, Jia-He Wang, Chueh-Chen Chen, Hong-Yo Kang
Summary: The study revealed that dysregulated expression of miR-146b and androgen receptor (AR) played critical roles in the tumorigenesis of papillary thyroid carcinoma (PTC). It was confirmed that miR-146b expression was significantly inversely correlated with AR expression. Further experiments showed that AR might bind to the androgen receptor element on the promoter region of miR-146b, leading to repression of miR-146b expression and reduction of PTC tumor aggressiveness. PTC patients with low AR/high miR-146b expression were associated with advanced tumor characteristics.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Biology
Yanis Zekri, Romain Guyot, Ines Garteizgogeascoa Suner, Laurence Canaple, Amandine Gautier Stein, Justine Vily Petit, Denise Aubert, Sabine Richard, Frederic Flamant, Karine Gauthier
Summary: This study used transcriptome and cistrome analyses to identify direct target genes of thyroid hormone (T3) in brown adipocytes and developed a new mouse model to study the role of T3 in brown adipose tissue (BAT). The results showed that T3 plays a crucial role in regulating lipid and glucose metabolism and BAT proliferation, providing new insights into the pathways by which T3 activates energy expenditure through adaptive thermogenesis in BAT.
Article
Endocrinology & Metabolism
Rutchanna M. S. Jongejan, Marcel E. Meima, W. Edward Visser, Tim I. M. Korevaar, Sjoerd A. A. van den Berg, Robin P. Peeters, Yolanda B. de Rijke
Summary: This study determined the distribution and binding affinity of thyroid hormone metabolites to thyroid hormone distributor proteins, and found that the distribution of metabolites differs from that of thyroid hormones. This has potential clinical importance for the interpretation of thyroid hormone metabolism.
Article
Biochemistry & Molecular Biology
Alaleh Zati Zehni, Falk Batz, Aurelia Vattai, Till Kaltofen, Svenja Schrader, Sven-Niclas Jacob, Jan-Niclas Mumm, Helene Hildegard Heidegger, Nina Ditsch, Sven Mahner, Udo Jeschke, Theresa Vilsmaier
Summary: This study aimed to evaluate the prognostic value of steroid hormone receptor expression in breast cancer patients, focusing on the retinoid X receptor (RXR) and thyroid hormone receptors (THRs). The analysis showed significant correlations between RXR and THRs expression and survival in different breast cancer entities. The findings suggest the need for further investigation into molecular therapies targeting steroid hormone receptors in breast cancer treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Environmental Sciences
Wei Wang, Qiyao Ma, Xinliang Ding, Yihua Xu, Mengting He, Jie Xu, Jianjun Liu, Cheng Ji, Jie Zhang
Summary: This study found that exposure to Bromoacetamide (BAcAm) can cause developmental toxicity in zebrafish embryos, possibly by disrupting thyroid hormone homeostasis.
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
(2022)
Review
Pharmacology & Pharmacy
Qianyu Tang, Min Zeng, Linxi Chen, Nian Fu
Summary: This review discusses the role of the thyroid hormone/thyroid hormone receptor axis in liver diseases, including its beneficial effects on metabolic-associated fatty liver disease, hepatitis, liver fibrosis, and liver injury, as well as its detrimental effects on the progression of acute liver failure and alcoholic liver disease. Moreover, the TH/TR axis exhibits paradoxical roles in hepatocellular carcinoma.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Barbara Lisowska-Myjak, Agnieszka Strawa, Hanna Zborowska, Artur Jakimiuk, Ewa Skarzynska
Summary: Establishing associations between serum parameters of thyroid function and serum proteins during pregnancy can help understand the role of the thyroid gland in regulating pregnancy-specific metabolic processes, and potentially identify candidate biomarkers for clinical assessment. The correlations between thyroid hormones and serum proteins suggest a shared biological role in maintaining maternal homeostasis, with potential for use as a biomarker panel in clinical settings. Negative correlations between fT3 and CER in the second trimester may reflect active regulation of metabolic processes.
SCIENTIFIC REPORTS
(2021)
Article
Endocrinology & Metabolism
Junpei Sanada, Fuminori Tatsumi, Shinji Kamei, Yoshiro Fushimi, Masashi Shimoda, Kenji Kohara, Shuhei Nakanishi, Kohei Kaku, Tomoatsu Mune, Hideaki Kaneto
Summary: Pituitary adenoma producing both growth hormone (GH) and thyroid-stimulating hormone (TSH) is rare but possible. This case study presented a 27-year-old woman with symptoms of acromegaly and simultaneous production of both GH and TSH by the pituitary adenoma. Treatment included pituitary tumor resection, cyber knife therapy, somatostatin analog, GH receptor antagonist, and anti-thyroid drug thiamazole.
FRONTIERS IN ENDOCRINOLOGY
(2021)
Review
Endocrinology & Metabolism
Matti L. Gild, Mark Stuart, Roderick J. Clifton-Bligh, Audrey Kinahan, David J. Handelsman
Summary: Abuse of hormones is common in elite sports, with androgens and erythropoietin being the most prohibited substances. The prohibition of thyroid hormone (TH) use remains controversial, but based on present data, it is neither justified nor feasible to prohibit TH in elite sports.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Engineering, Environmental
Jian Li, Ying Xu, Na Li, Rui Zuo, Yuanzheng Zhai, Haiyang Chen
Summary: Through integrated in vitro, in vivo, and in silico assays, the study investigated the thyroid hormone-disrupting effects and mechanisms of 8 typical organophosphate esters (OPEs). It was found that these chemicals competitively bound to the membrane thyroid hormone receptor (mTR) and some OPEs also interacted with the nuclear thyroid hormone receptor (nTR). Molecular docking simulation supported these findings. In addition, in vivo analyses using zebrafish embryo development demonstrated the thyroid hormone-disrupting effects of OPEs and their possible association with mTR.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Richard Sinko, Kristof Rada, Anna Kollar, Petra Mohacsik, Miklos Tenk, Csaba Fekete, Balazs Gereben
Summary: Thyroid hormone signaling is important for normal tissue function, and environmental pollutants can disrupt endocrine functions. This study used a mouse model to investigate the effects of two chemical pollutants on thyroid hormone action in different tissues. The results showed that the pollutants had different effects on different tissues, and the mouse model proved to be useful for identifying thyroid hormone disruptors and their tissue-specific effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Endocrinology & Metabolism
Limei Li, Yan Song, Yongquan Shi, Liangliang Sun
Summary: Nonalcoholic fatty liver disease (NAFLD) is a metabolic liver disease without a known cause or FDA-approved drug treatment. Hypothyroidism has been identified as a risk factor for NAFLD, as thyroid hormone (TH) is important for metabolism regulation in adults. Thyroxine, a synthetic TH, has been shown to reduce liver fat in animal models with NAFLD, but it has side effects, especially in the heart. To overcome these side effects, agonists specific to the TR beta, a subtype of the TH receptor mainly expressed in the liver, have been developed and shown positive therapeutic effects in NAFLD animal models and clinical trials. This review aims to provide an updated reference and explore the future therapeutic potential of TR beta-specific agonists in the treatment of NAFLD.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Biochemistry & Molecular Biology
Ichiro Yamauchi, Yoriko Sakane, Takafumi Yamashita, Takuro Hakata, Taku Sugawa, Haruka Fujita, Kentaro Okamoto, Daisuke Taura, Keisho Hirota, Yohei Ueda, Toshihito Fujii, Akihiro Yasoda, Nobuya Inagaki
Summary: This study aimed to investigate the effects of peripheral iodothyronine deiodinases (DIOs) on thyroid hormone economy. The results showed that D2 could enhance local thyroid hormone action and promote its circulation, while D3 could decrease circulating T3 and T4 levels with elevated reverse T3, leading to consumptive hypothyroidism. Additionally, the D3 mice are expected to be a novel hypothyroidism model.
Article
Endocrinology & Metabolism
Cristina Luongo, Cecilia Martin, Kristen Vella, Alessandro Marsili, Raffaele Ambrosio, Monica Dentice, John W. Harney, Domenico Salvatore, Ann Marie Zavacki, P. Reed Larsen
Article
Endocrinology & Metabolism
Georg Brabant, Robin P. Peeters, Shiao Y. Chan, Juan Bernal, Philippe Bouchard, Domenico Salvatore, Kristien Boelaert, Peter Laurberg
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2015)
Article
Endocrinology & Metabolism
Luciana A. Castroneves, Rebecca H. Jugo, Michelle A. Maynard, Jennifer S. Lee, Ari J. Wassner, David Dorfman, Roderick T. Bronson, Chinweike Ukomadu, Agoston T. Agoston, Lai Ding, Cristina Luongo, Cuicui Guo, Huaidong Song, Valeriy Demchev, Nicholas Y. Lee, Henry A. Feldman, Kristen R. Vella, Roy W. Peake, Christina Hartigan, Mark D. Kellogg, Anal Desai, Domenico Salvatore, Monica Dentice, Stephen A. Huang
Article
Endocrinology & Metabolism
Darius K. L. Aw, Rohit A. Sinha, Hong Chang Tan, Lih Ming Loh, Domenico Salvatore, Paul M. Yen
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2014)
Review
Endocrinology & Metabolism
Domenico Salvatore, Warner S. Simonides, Monica Dentice, Ann Marie Zavacki, P. Reed Larsen
NATURE REVIEWS ENDOCRINOLOGY
(2014)
Review
Endocrinology & Metabolism
Annarita Nappi, Maria Angela De Stefano, Monica Dentice, Domenico Salvatore
Summary: Hormones play a key role in cancer development, and the alteration of intratumoral thyroid hormone concentration is a common feature in many human tumors. Deiodinases are crucial for cell-autonomous control of TH action, and their expression is often altered in tumors. Studies have shown a dynamic expression of deiodinases in cancer cells, influenced by a network of factors, which exposes cancer cells to varying concentrations of TH with functional implications on cellular functions.
Review
Endocrinology & Metabolism
Domenico Salvatore, Massimo Santoro, Martin Schlumberger
Summary: Alterations of RET kinase have been found in diverse thyroid cancer subtypes, including gene rearrangements and mutations. RET kinase inhibitors are an attractive therapeutic target for patients with RET alterations, showing promising results in the treatment of advanced thyroid cancer.
NATURE REVIEWS ENDOCRINOLOGY
(2021)
Article
Health Care Sciences & Services
Teresa Troiani, Stefania Napolitano, Gabriella Brancaccio, Valentina Belli, Annarita Nappi, Caterina Miro, Domenico Salvatore, Monica Dentice, Michele Caraglia, Renato Franco, Emilio Francesco Giunta, Vincenzo De Falco, Davide Ciardiello, Fortunato Ciardiello, Giuseppe Argenziano
Summary: Melanoma, the most lethal form of skin cancer, has seen a revolution in therapeutic options in the past decade with the introduction of targeted therapies and immune-checkpoint inhibitors. However, patients with advanced disease require new treatment options. A clinical case highlighted the successful treatment of a melanoma patient with the SMO p.Gln216Arg mutation using imiquimod, shedding light on a potentially druggable target for melanoma patients.
JOURNAL OF PERSONALIZED MEDICINE
(2021)
Review
Biochemistry & Molecular Biology
Maria Angela De Stefano, Raffaele Ambrosio, Tommaso Porcelli, Gianfranco Orlandino, Domenico Salvatore, Cristina Luongo
Summary: Skeletal muscle atrophy is characterized by altered protein turnover, with protein degradation exceeding synthesis, leading to muscle mass loss and weakness. Thyroid hormone plays a key role, regulating TH levels in muscle through deiodinases. Modulation of deiodinases may offer a therapeutic approach for treating muscle atrophy.
Article
Endocrinology & Metabolism
Tatiana L. Fonseca, Samuel C. Russo, Cristina Luongo, Domenico Salvatore, Antonio C. Bianco
Summary: Inactivation of Dio3 in brown adipose tissue during embryonic development leads to premature exposure to thyroid hormone (T3) signaling, resulting in early adipocyte development and gene expression. BAT-D3KO mice show changes in weight, adipocyte area, and gene expression related to mitochondria, fat, and glucose homeostasis. However, their energy expenditure and ability to maintain core temperature remain normal.
Article
Oncology
Tommaso Porcelli, Raffaele Ambrosio, Maria Angela De Stefano, Cristina Luongo, Daniela Terracciano, Caterina Miro, Monica Dentice, Martin Schlumberger, Domenico Salvatore
Summary: In this study, the authors investigated the effect of vandetanib, a multi-kinase inhibitor, on the expression and activity of deiodinase enzymes responsible for thyroid hormone metabolism. They found that vandetanib specifically downregulated the expression of type 2 deiodinase and reduced its activity in fibro/adipogenic progenitor cells. These findings provide insights into the mechanisms by which TKIs induce hypothyroidism and identify a specific cell population involved in this effect.
ENDOCRINE-RELATED CANCER
(2023)
Review
Oncology
Maria Angela De Stefano, Tommaso Porcelli, Martin Schlumberger, Domenico Salvatore
Summary: The three deiodinase selenoenzymes play an important role in regulating intracellular thyroid hormone levels. Different types of deiodinases are expressed during different stages of thyroid tumorigenesis, contributing to customized intracellular thyroid hormone signaling in cancer cells. Understanding the functions of thyroid hormones in different stages of thyroid cancers is crucial.
ENDOCRINE-RELATED CANCER
(2023)
Article
Oncology
Maria Angela De Stefano, Tommaso Porcelli, Raffaele Ambrosio, Cristina Luongo, Maddalena Raia, Martin Schlumberger, Domenico Salvatore
Summary: D2 is highly expressed in anaplastic thyroid cancer cells and is essential for their proliferation and invasiveness. Inhibition of D2 leads to cell growth arrest and senescence, as well as reduced migration and invasion. Mutated p53(72R(R248W)) can induce D2 expression in transfected papillary thyroid cancer cells. These findings suggest that D2 is a potential therapeutic target for the treatment of anaplastic thyroid cancer.
ENDOCRINE-RELATED CANCER
(2023)
Article
Biochemistry & Molecular Biology
Warner Simonides, Alice Tijsma, Anita Boelen, Rutchanna Jongejan, Yolanda de Rijke, Robin Peeters, Monica Dentice, Domenico Salvatore, Alice Muller
Summary: Chronic hemodynamic overload of the heart can lead to compensatory or decompensated ventricular hypertrophy and heart failure, which is partly due to a reduction in cardiac thyroid-hormone (TH) action. Increased expression of the TH-inactivating enzyme deiodinase type 3 (D3) and reduced plasma TH levels contribute to the decrease in cardiac TH levels. The study showed that decompensated LV hypertrophy with diminished cardiac output is associated with a greater reduction of cardiac TH levels than compensated hypertrophy with maintained cardiac output, and changes in systemic TH homeostasis play a role in the impairment of ventricular function in decompensated hypertrophy.
Article
Oncology
Cristina Luongo, Tommaso Porcelli, Francesca Sessa, Maria Angela De Stefano, Francesco Scavuzzo, Vincenzo Damiano, Michele Klain, Claudio Bellevicine, Elide Matano, Giancarlo Troncone, Martin Schlumberger, Domenico Salvatore
Summary: The case study describes a rare variant of anaplastic thyroid cancer in a 54-year-old woman, who initially responded well to a combination treatment of surgery, radiation therapy, and chemotherapy, and later received lenvatinib and pembrolizumab with a sustained partial tumor response. Paucicellular ATC may exhibit less aggressive behavior initially but can progress rapidly over time, with the combination of lenvatinib and pembrolizumab showing effectiveness as salvage therapy for an extended period.
