Thyrostimulin (a TSH-like Hormone) Expression in Orbital and Thyroid Tissue

Lantz, Mikael; Vondrichova, Tereza; Capretz, Annika de; Nilsson, Elisabet M.; Frenander, Christofer; Bondeson, Anne‐Greth; Ridderstråle, Martin; Åberg, Magnus; Åsman, Peter; Groop, Leif; Hallengren, Bengt

doi:10.1089/thy.2006.0155

Cited by 8 publications

(5 citation statements)

References 15 publications

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“…We showed that thyrostimulin is unlikely to play a role in the orbit, although we could not exclude thyrostimulin production [14] by other orbital components not studied. Our results are consistent with those of Lantz et al, who also investigated orbital tissues [25]. Both orbital studies contrast with the work of Sun et al, who showed that thyrostimulin functions as an ovarian paracrine regulator [26], and also of Bassett et al, who reported the regulation of osteoblast formation in bone by thyrostimulin in early life [15].…”

Section: Discussionsupporting

confidence: 92%

Expression of Endogenous Putative TSH Binding Protein in Orbit

Draman

Grennan-Jones

Taylor

et al. 2021

CIMB

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Thyroid stimulating antibodies (TSAB) cause Graves’ disease and contribute to Graves’ Orbitopathy (GO) pathogenesis. We hypothesise that the presence of TSH binding proteins (truncated TSHR variants (TSHRv)) and/or nonclassical ligands such as thyrostimulin (α2β5) might provide a mechanism to protect against or exacerbate GO. We analysed primary human orbital preadipocyte-fibroblasts (OF) from GO patients and people free of GO (non-GO). Transcript (QPCR) and protein (western blot) expression levels of TSHRv were measured through an adipogenesis differentiation process. Cyclic-AMP production by TSHR activation was studied using luciferase-reporter and RIA assays. After differentiation, TSHRv levels in OF from GO were significantly higher than non-GO (p = 0.039), and confirmed in ex vivo analysis of orbital adipose samples. TSHRv western blot revealed a positive signal at 46 kDa in cell lysates and culture media (CM) from non-GO and GO-OF. Cyclic-AMP decreased from basal levels when OF were stimulated with TSH or Monoclonal TSAB (M22) before differentiation protocol, but increased in differentiated cells, and was inversely correlated with the TSHRv:TSHR ratio (Spearman correlation: TSH r = −0.55, p = 0.23, M22 r = 0.87, p = 0.03). In the bioassay, TSH/M22 induced luciferase-light was lower in CM from differentiated GO-OF than non-GO, suggesting that secreted TSHRv had neutralised their effects. α2 transcripts were present but reduced during adipogenesis (p < 0.005) with no difference observed between non-GO and GO. β5 transcripts were at the limit of detection. Our work demonstrated that TSHRv transcripts are expressed as protein, are more abundant in GO than non-GO OF and have the capacity to regulate signalling via the TSHR.

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Section: Discussionsupporting

confidence: 92%

Expression of Endogenous Putative TSH Binding Protein in Orbit

Draman

Grennan-Jones

Taylor

et al. 2021

CIMB

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“…Thyrostimulin expression has been investigated in several species ( 1 , 4 , 7 , 12 – 14 ), and, in common with other glycoprotein hormones, GPA2 and GPB5 were initially found to be coexpressed in the pituitary ( 1 , 4 , 13 ). However, studies in Drosophila melanogaster , Caenorhabditis elegans , Amphioxus , and mouse indicated a broader developmental role for GPA2 and GPB5 ( 5 , 15 – 17 ) and also suggested the subunits might act independently as monomers or homodimers ( 5 ).…”

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confidence: 99%

Thyrostimulin Regulates Osteoblastic Bone Formation During Early Skeletal Development

et al. 2015

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The ancestral glycoprotein hormone thyrostimulin is a heterodimer of unique glycoprotein hormone subunit alpha (GPA)2 and glycoprotein hormone subunit beta (GPB)5 subunits with high affinity for the TSH receptor. Transgenic overexpression of GPB5 in mice results in cranial abnormalities, but the role of thyrostimulin in bone remains unknown. We hypothesized that thyrostimulin exerts paracrine actions in bone and determined: 1) GPA2 and GPB5 expression in osteoblasts and osteoclasts, 2) the skeletal consequences of thyrostimulin deficiency in GPB5 knockout (KO) mice, and 3) osteoblast and osteoclast responses to thyrostimulin treatment. Gpa2 and Gpb5 expression was identified in the newborn skeleton but declined rapidly thereafter. GPA2 and GPB5 mRNAs were also expressed in primary osteoblasts and osteoclasts at varying concentrations. Juvenile thyrostimulin-deficient mice had increased bone volume and mineralization as a result of increased osteoblastic bone formation. However, thyrostimulin failed to induce a canonical cAMP response or activate the noncanonical Akt, ERK, or mitogen-activated protein kinase (P38) signaling pathways in primary calvarial or bone marrow stromal cell-derived osteoblasts. Furthermore, thyrostimulin did not directly inhibit osteoblast proliferation, differentiation or mineralization in vitro. These studies identify thyrostimulin as a negative but indirect regulator of osteoblastic bone formation during skeletal development.

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“…An ABI 900 was used to perform the quantitative RT-PCR using primer and probe sets from Applied Biosystems. The housekeeping gene that was used was cyclophilin A (12). …”

Section: Methodsmentioning

confidence: 99%

Inflammatory characteristics of adipose tissue collected by surgical excision vs needle aspiration

et al. 2014

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Subcutaneous adipose tissue can be obtained for research during an elective, clinically indicated operation by standard surgical excision approaches and by needle aspiration in pure research settings. Whether measurements of inflammatory markers and cells made in tissue collected these two different ways are comparable is debatable. We sought to determine whether these two techniques yield systematically different results for measurements of inflammation, cellular senescence, and adipose tissue composition. Twelve subjects undergoing surgery participated. At the time of surgery abdominal subcutaneous adipose tissue from adjacent sites was removed by excision and needle aspiration. Stromovascular cell composition (flow cytometry), the number of senescent cells (senescence-associated-β-galactosidase staining), and IL-6, IL-1, TNF-α, MCP1 mRNA (RT-PCR) were measured in each sample. We found no statistically significant differences between the two sample collection approaches for any of the parameters measured. We conclude that these two methods of obtaining adipose tissue do not systematically differ in the results of cytokine mRNA content, cellular senescence, or stromovascular cell composition.

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Thyrostimulin (a TSH-like Hormone) Expression in Orbital and Thyroid Tissue

Abstract: Neither did we demonstrate gene expression of thyrostimulin in intraorbital adipose tissue or in thyroid tissue, nor could we confirm earlier findings in rat thyroid tissue. Whether thyrostimulin is a regulator of thyroid function has to be further investigated in future studies.

Cited by 8 publications

References 15 publications

Expression of Endogenous Putative TSH Binding Protein in Orbit

Expression of Endogenous Putative TSH Binding Protein in Orbit

Thyrostimulin Regulates Osteoblastic Bone Formation During Early Skeletal Development

Inflammatory characteristics of adipose tissue collected by surgical excision vs needle aspiration

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