TSH Is a Negative Regulator of Skeletal Remodeling

Abe, Etsuko; Marians, Russell; Yu, Wanqin; Xue, Wenrui; Ando, Takao; Li, Yanan; Iqbal, Jameel; Eldeiry, Leslie S.; Rajendren, Gopalan; Blair, Harry C.; Davies, Terry F.; Zaidi, Mone

doi:10.1016/s0092-8674(03)00771-2

Cited by 602 publications

(574 citation statements)

References 40 publications

Supporting

Mentioning

532

Contrasting

Unclassified

Order By: Relevance

“…We suggest that vertebrate T cell differentiation and activation are controlled, at least in part, by thyroid axis hormones regardless of the location or origin of the T cells (thymus, lymph node, spleen, or intestine). The findings reported here, as well as those demonstrating a direct role for TSH in bone remodeling [41], add to the growing body of information indicating that TSH is a multidimensional molecule with properties that extend beyond the neuroendocrine system [42]. Three-color staining of small intestinal IELs for expression of TSHR, CD4, and CD8.…”

Section: Discussionsupporting

confidence: 58%

Intestinal TSH production is localized in crypt enterocytes and in villus ‘hotblocks’ and is coupled to IL-7 production: evidence for involvement of TSH during acute enteric virus infection

et al. 2005

View full text Add to dashboard Cite

The immune and neuroendocrine systems have been shown to work conjointly in a number of ways. One aspect of this has to do with a potential role for thyroid stimulating hormone (TSH) in the regulation of the mucosal immune system, although the mechanisms by which this occurs remain vague. To more thoroughly understand how TSH participates in intestinal intraepithelial lymphocyte (IEL) development and immunity, experiments have been conducted to define local sites of intestinal TSH production, and to characterize changes that occur in the synthesis of TSH during acute enteric virus infection. Here, we demonstrate that TSH in the small intestine is specifically localized to regions below villus crypts as seen by immunocytochemical staining, which revealed high-level TSH staining in lower crypts in the absence of IL-7 staining, and TSH and IL-7 costaining in upper crypt regions. Additionally, prominent TSH staining was evident in TSH 'hotblocks' sparsely dispersed throughout the epithelial layer. In rotavirus-infected mice, the TSH staining pattern differed significantly from that of non-infected animals. Notably, at 2 and 3 days post-infection, TSH expression was high in and near apical villi where virus infection was greatest. These findings lend credence to the notion that TSH plays a role both in the development of intestinal T cells, and in the process of local immunity during enteric virus infection.

show abstract

Section: Discussionsupporting

confidence: 58%

Intestinal TSH production is localized in crypt enterocytes and in villus ‘hotblocks’ and is coupled to IL-7 production: evidence for involvement of TSH during acute enteric virus infection

et al. 2005

View full text Add to dashboard Cite

show abstract

“…Also, TSH is reported to have a direct effect on bone turnover through TSHRs on osteoblasts and osteoclasts (37). However, other that the shortening of a few facial bones, the skeletons of OGH-TG mice are normal.…”

Section: Resultsmentioning

confidence: 99%

Resistance to diet-induced obesity in mice globally overexpressing OGH/GPB5

Macdonald

Wortley

Gowen

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

We identified a glycoprotein hormone ␤-subunit (OGH, also called GPB5) that, as a heterodimer with the ␣-subunit GPA2, serves as a second ligand for the thyroid-stimulating hormone receptor. Mice in which the OGH gene is deleted (OGH ؊/؊ ) are indistinguishable from WT littermates in body weight, response to high-fat diet, metabolic parameters, body composition, and insulin tolerance. Mice engineered to transgenically globally overexpress OGH (OGH-TG) develop Ϸ2-fold elevations in their basal thyroid levels and weigh slightly less than WT littermates despite increased food intake because of an increase in their metabolic rates. Moreover, when OGH-TG mice are challenged with a high-fat diet, they gain significantly less weight and body fat than their WT littermates. The OGH-TG mice also have reduced blood glucose, insulin, cholesterol, and triglycerides. In contrast to other approaches in which the thyroid axis is activated, OGH-TG mice exhibit only minor changes in heart rate and blood pressure. Our findings suggest that constitutive low-level activation of the thyroid axis (via OGH or other means) may provide a beneficial therapeutic approach for combating diet-induced obesity.cholesterol ͉ metabolic rate ͉ thyroid T hyroid-stimulating hormone (TSH) and the TSH receptor (TSHR) are key proteins in the control of thyroid function. TSH synthesis and release is stimulated by hypothalamic TSHreleasing hormone (TRH) and is down-regulated (inhibited) by thyroid hormone in a classic endocrine negative-feedback loop. The specificity inherent in TSH resides in its unique ␤-subunit that heterodimerizes with a common ␣-subunit, which it shares with the other glycoprotein hormones [i.e., follicle-stimulating hormone (FSH), luteinizing hormone, and chorionic gonadotropin]. The primary physiological actions of TSH on the thyroid are stimulation of the synthesis and release of 3,5,3Ј,5Ј-tetraiodo-L-thyronine (T4) and 3,5,3Ј-triiodo-L-thyronine (T3) (together termed thyroid hormone) and promotion of thyroid growth; for example, it has been shown that thyroid development is arrested in mice with targeted disruption of the common ␣-subunit (1).Clinically, thyroid hormone is used primarily as a replacement therapy for the patients with hypothyroidism, and it has been considered as a possible therapy for weight reduction (because of its ability to increase metabolism and energy expenditures), for lowering cholesterol, and even to build bone (in osteoporosis). One of the major hurdles in this approach has been the cardiovascular toxicity observed after administration of the endogenous ligands T4 and T3 or nonselective thyroid hormone agonists. The two major subtypes of the thyroid hormone receptors that mediate these responses, TR␣ and TR␤, are the products of different genes and are also differentially processed to each yield two isoforms. It has been argued that modulation of heart rate and rhythm is mediated predominantly by activation of TR␣ 1 (2-4), and as a result, recent pharmaceutical research efforts have focused on develop...

show abstract

“…Increasing data showed that the TSHR was also expressed in many nonthyroid tissues, and it might actually play a physiological role in these tissues. 8,9 We recently demonstrated that TSHR was expressed in hepatocytes and that stimulation of cultured liver cells with TSH increased the production of cAMP. 10 These results suggested that the TSHR might play an important role in the regulation of liver function.…”

mentioning

confidence: 99%

A Novel Role for Thyroid-Stimulating Hormone: Up-Regulation of Hepatic 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A Reductase Expression Through the Cyclic Adenosine Monophosphate/Protein Kinase A/Cyclic Adenosine Monophosphate–Responsive Element Binding Protein Pathway

et al. 2010

View full text Add to dashboard Cite

Elevated thyroid-stimulating hormone (TSH) and hypercholesterolemia commonly coexist, as typically seen in hypothyroidism, but there is no known mechanism directly linking the two. Here, we demonstrated that in liver cells, TSH promoted the expression of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase (HMGCR), a rate-limiting enzyme in cholesterol synthesis, by acting on the TSH receptor in hepatocyte membranes and stimulating the cyclic adenosine monophosphate / protein kinase A / cyclic adenosine monophosphate-responsive element binding protein (cAMP/PKA/CREB) signaling system. In thyroidectomized rats, the production of endogenous thyroid hormone was eliminated and endogenous TSH was suppressed through pituitary suppression with constant administration of exogenous thyroid hormone, and hepatic HMGCR expression was increased by administration of exogenous TSH. These results suggested that TSH could up-regulate hepatic HMGCR expression, which indicated a potential mechanism for hypercholesterolemia involving direct action of TSH on the liver. (HEPATOLOGY 2010;52:1401-1409 H ypothyroidism is well known to be associated with elevated serum TC, which can result in hypercholesterolemia. 1,2 The underlying mechanism is widely thought to be TH deficiency.However, elevation of serum TC has also been observed in patients with subclinical hypothyroidism (SCH), in which TSH is elevated but TH stays within its normal range. 1,3,4 Thus, the development of

show abstract

TSH Is a Negative Regulator of Skeletal Remodeling

Cited by 602 publications

References 40 publications

Intestinal TSH production is localized in crypt enterocytes and in villus ‘hotblocks’ and is coupled to IL-7 production: evidence for involvement of TSH during acute enteric virus infection

Intestinal TSH production is localized in crypt enterocytes and in villus ‘hotblocks’ and is coupled to IL-7 production: evidence for involvement of TSH during acute enteric virus infection

Resistance to diet-induced obesity in mice globally overexpressing OGH/GPB5

A Novel Role for Thyroid-Stimulating Hormone: Up-Regulation of Hepatic 3-Hydroxy-3-Methyl-Glutaryl-Coenzyme A Reductase Expression Through the Cyclic Adenosine Monophosphate/Protein Kinase A/Cyclic Adenosine Monophosphate–Responsive Element Binding Protein Pathway

Contact Info

Product

Resources

About