Functional human TSHβ splice variant produced by plasma cell may be involved in the immunologic injury of thyroid in the patient with Hashimoto's thyroiditis

Liu, Chunrong; Miao, Jun; Zhao, Zhan-kao; Li, Lanying; Liu, Yamin; Zhang, Yongliang; Li, Xuehua; Liu, Yanqing; Gu, Yue; Zhao, Yue; Luo, Jian-wen

doi:10.1016/j.mce.2015.06.009

Cited by 8 publications

(12 citation statements)

References 18 publications

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“…TSH, secreted by the anterior pituitary, is known to induce the TSHβ splice variant was also expressed in plasma cells of the thyroid of a patient with Hashimoto's thyroiditis (15). However, whether the production of extrapituitary TSHβ splice variant promotes alterations in thyroid hormone synthesis, similar to pituitary TSH, is yet to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

HPT axis‑independent TSHβ splice variant regulates the synthesis of thyroid hormone in mice

et al. 2019

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Thyroid stimulating hormone (TSH) consists of an α-subunit and a unique β-subunit. The first in-frame TSHβ splice variant produced by the cells of immune system was identified in 2009. The TSHβ splice variant and native TSHβ exhibit different expression profiles, and research has been conducted to elucidate the role of the TSHβ splice variant in different diseases. However, understanding of the fundamental physiological characteristics of the TSHβ splice variant is currently limited. To verify whether the TSHβ splice variant has the potential to induce thyroid follicular cells to synthesize thyroid hormone, in vivo and in vitro stimulation experiments were conducted in the present study. A total of 60 C57BL/6 mice were divided into control-, 5 and 10 µg TSHβ splice variant-treated groups at random. Mice were sacrificed at 0.5, 1 and 4 h after intraperitoneal injection, and serum levels of tri-iodothyronine (T3) and thyroxine (T4) were determined using a radioimmunoassay. Thyroid follicular cells were isolated from the thyroids of mice, and stimulated with 2 µg/ml TSHβ splice variant. Supernatants were collected, and the levels of T3 and T4 were detected. The protein expression levels of the sodium-iodide symporter, thyroperoxidase and thyroglobulin in thyroid follicular cells were quantified using western blot analysis. To verify whether the TSHβ splice variant expression was regulated by the hypothalamus-pituitary-thyroid (HPT) axis, similar to native TSHβ, a total of 60 C57BL/6 mice were equally divided into control, 2 mg/kg T3 intraperitoneal injection and 0.05 mg/kg thyroid-releasing hormone intraperitoneal injection groups at random. Mice were sacrificed at 1 and 4 h after injection. Alterations in the expression of the TSHβ splice variant in the pituitary, thyroid, peripheral blood leukocytes and spleen tissues were detected using western blot analysis. The present study demonstrated that the TSHβ splice variant is not regulated by the HPT axis and may affect thyroid hormone synthesis. Modifications in the expression of the TSHβ splice variant may occur in a uniquely regulated manner to provide peripheral immunological compartments with a source of activated cells, particularly under immune stress.

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Section: Discussionmentioning

confidence: 99%

HPT axis‑independent TSHβ splice variant regulates the synthesis of thyroid hormone in mice

et al. 2019

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“…Bone marrow cells were shown to express very little amount of the GPHα subunit ( 198 ) if any ( 202 ). Even if some role has been attributed to the truncated variant from macrophages in osteoprotection ( 202 ), in immune response with the variant expressed in leucocytes homing to the thyroid after systemic bacterial infection ( 199 , 203 ) and in the pathology of Hashimoto’s Thyroiditis patients ( 205 ), the way this variant may achieve these functions remains to be deciphered. It has to be reminded that the TSHβ variant consists of part of the last intron directly attached to the last exon of the tshb .…”

Section: Unconventional Actions Of Gphs or Their Subunitsmentioning

confidence: 99%

Unconventional Actions of Glycoprotein Hormone Subunits: A Comprehensive Review

Quérat

2021

Front. Endocrinol.

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The glycoprotein hormones (GPH) are heterodimers composed of a common α subunit and a specific β subunit. They act by activating specific leucine-rich repeat G protein-coupled receptors. However, individual subunits have been shown to elicit responses in cells devoid of the receptor for the dimeric hormones. The α subunit is involved in prolactin production from different tissues. The human chorionic gonadotropin β subunit (βhCG) plays determinant roles in placentation and in cancer development and metastasis. A truncated form of the thyrotropin (TSH) β subunit is also reported to have biological effects. The GPH α- and β subunits are derived from precursor genes (gpa and gpb, respectively), which are expressed in most invertebrate species and are still represented in vertebrates as GPH subunit paralogs (gpa2 and gpb5, respectively). No specific receptor has been found for the vertebrate GPA2 and GPB5 even if their heterodimeric form is able to activate the TSH receptor in mammals. Interestingly, GPA and GPB are phylogenetically and structurally related to cysteine-knot growth factors (CKGF) and particularly to a group of antagonists that act independently on any receptor. This review article summarizes the observed actions of individual GPH subunits and presents the current hypotheses of how these actions might be induced. New approaches are also proposed in light of the evolutionary relatedness with antagonists of the CKGF family of proteins.

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“…Until recently, no functional isoforms of TSHβ had been identified. We characterized a unique in-frame splice variant of TSHβ (referred to as TSHβv), which is copiously made by PBL and BM hematopoietic cells, in particular though not exclusively on myeloid cells ( 8 , 38 – 40 ). Notably, TSHβv is stored in intracellular secretory vesicles in macrophages ( 39 ), a property that would facilitate rapid release under appropriate conditions.…”

Section: A Novel Tshβ Isoform Produced By the Central And Peripheral mentioning

confidence: 99%

“…Treatment of patients with prednisone reduced TSHβv transcript levels in persons with short duration of disease compared to persons with long duration. Additionally, TSHβv-producing plasma cells infiltrated the thyroid in HT patients ( 40 ). Recent studies demonstrate that immune system TSHβv in humans operates independently of the HPT axis and is capable of inducing TH synthesis from PBL in times of immune stress, such as during systemic infection ( 44 ).…”

Section: A Novel Tshβ Isoform Produced By the Central And Peripheral mentioning

confidence: 99%

Dynamic Interactions Between the Immune System and the Neuroendocrine System in Health and Disease

Klein

2021

Front. Endocrinol.

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The immune system and the neuroendocrine system share many common features. Both consist of diverse components consisting of receptors and networks that are widely distributed throughout the body, and both sense and react to external stimuli which, on the one hand control mechanisms of immunity, and on the other hand control and regulate growth, development, and metabolism. It is thus not surprising, therefore, that the immune system and the neuroendocrine system communicate extensively. This article will focus on bi-directional immune-endocrine interactions with particular emphasis on the hormones of the hypothalamus-pituitary-thyroid (HPT) axis. New findings will be discussed demonstrating the direct process through which the immune system-derived thyroid stimulating hormone (TSH) controls thyroid hormone synthesis and bone metamorphosis, particularly in the context of a novel splice variant of TSHβ made by peripheral blood leukocytes (PBL). Also presented are the ways whereby the TSHβ splice variant may be a contributing factor in the development and/or perpetuation of autoimmune thyroid disease (AIT), and how systemic infection may elicit immune-endocrine responses. The relationship between non-HPT hormones, in particular adipose hormones, and immunity is discussed.

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Functional human TSHβ splice variant produced by plasma cell may be involved in the immunologic injury of thyroid in the patient with Hashimoto's thyroiditis

Cited by 8 publications

References 18 publications

HPT axis‑independent TSHβ splice variant regulates the synthesis of thyroid hormone in mice

HPT axis‑independent TSHβ splice variant regulates the synthesis of thyroid hormone in mice

Unconventional Actions of Glycoprotein Hormone Subunits: A Comprehensive Review

Dynamic Interactions Between the Immune System and the Neuroendocrine System in Health and Disease

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