Virus Infection Activates Thyroid Stimulating Hormone Synthesis in Intestinal Epithelial Cells

[helvella]

OK - so this is in mice.

But the implications could be significant. Especially if the amount of TSH produced is anything like what the pituitary can produce.

Also whether thyroid hormone would affect production of TSH within intestinal epithelial cells? If so, the taking of any thyroid hormone orally (tablet or liquid or gel) could have impacts which might never have been considered. If such TSH is significant in protecting against infection, then oral thyroid hormones might suppress that - leaving us open to infections which could be anything from common through unusual to extremely rare.

Virus Infection Activates Thyroid Stimulating Hormone Synthesis in Intestinal Epithelial Cells

Shaun Varghese, Dina Montufar-Solis, Bryce H. Vincent, and John R. Klein

Department of Diagnostic Sciences, University of Texas Health Science Center at Houston, Houston, TX 77030

Abstract

The small intestine has been shown to be an extra-pituitary site of TSH (thyroid stimulating hormone) production, and previous in vivo studies have shown that TSH synthesis localizes within areas of enteric virus infection within the small intestine; however, the cellular source of intestinal TSH has not been adequately determined. In the present study, we have used the murine MODE-K small intestinal epithelial cell line to demonstrate both at the transcriptional level and as a secreted hormone, as measured in a TSHβ-specific enzyme-linked assay, that epithelial cells in fact respond to infection with reovirus serotype 3 Dearing strain by upregulating TSH synthesis. Moreover, sequence analysis of a PCR-amplified TSHβ product from MODE-K cells revealed homology to mouse pituitary TSHβ. These findings have direct functional implications for understanding a TSH immune-endocrine circuit in the small intestine.

Keywords: Immune-endocrine, sequence, gene, transcript, realtime PCR

Under normal physiological conditions, TSH (thyroid stimulating hormone) is produced by the anterior pituitary, whereupon it is used to regulate the synthesis and release of thyroid hormones. Although knowledge of an immune-endocrine network involving hormones of the hypothalamus-pituitary-thyroid axis dates back a number of years [Ajjan et al., 1996; Fabris et al., 1971; Pierpaoli and Besedovsky, 1975; Pierpaoli et al., 1977; Pierpaoli and Sorkin, 1972], many gaps in information exist as to the nature of this network. Tissues other than the pituitary are known to be capable of producing TSH [Kruger and Blalock, 1986; Kruger et al., 1989; Smith et al., 1983; Wang et al., 2003], and studies from our laboratory have described a TSH circuit in the small intestine that functions to regulate the differentiation and/or function of IELs (intestinal intraepithelial lymphocytes) [Wang and Klein, 1994; Wang and Klein, 1995; Wang et al., 1997]. Additionally, we recently demonstrated by immunocytochemical staining that mice infected with rotavirus, a member of the reoviridae family [Scofield et al., 2005], produced TSH in areas that co-localized with sites of infection. TSH levels are similarly upregulated in the intestine following reovirus infection [Klein, 2006]. However, because of the extensive heterogeneity of intestinal tissues in vivo, it was impossible to determine the cellular source of intestinal TSH in the context of virus infection. This is an important issue for elucidating TSH-mediated interactive mechanisms within that intestinal immune-endocrine pathway.

To resolve this, we have used the murine MODE-K small intestinal epithelial cell line to assess the ability of intestinal epithelial cells to produce TSH following infection with T3D reovirus (reovirus serotype 3 Dearing strain). The findings reported here unambiguously demonstrate that virus infection leads to an increase in TSH synthesis by intestinal epithelial cells, and we show that TSH produced by intestinal epithelial cells is homologous to the mRNA sequence of mouse pituitary TSH.

This link offers a PDF which is accessible (right now) but the published paper is paywalled!

ncbi.nlm.nih.gov/pmc/articl...

[tattybogle]

interesting to learn that TSH can be produced in other places , not just the pituitary .

On a similar/ related subject.....i was reading this the other day ( thanks to Asiatic for the link ) : ncbi.nlm.nih.gov/pmc/articl... The Mysterious Universe of the TSH Receptor (2022)

i hadn't realised how many other tissues apart from the thyroid have TSH Receptors ... i already knew the tissues around the eye have them but not the rest of it :

".... Several extrathyroidal locations of the receptor have been found including: the pituitary, the hypothalamus, and other areas of the central nervous system; the periorbital tissue; the skin; the kidney; the adrenal; the liver; the immune system cells; blood cells and vascular tissues; the adipose tissue; the cardiac and skeletal muscles, and the bone. Although the functionality of the receptor has been demonstrated in most of these tissues, its physiological importance is still a matter of debate. A contribution to several pathological processes is evident in some cases, as is the case of Grave’s disease in its multiple presentations. Conversely, in the context of other thyroid abnormalities, the contribution of the TSH-R and its ligand is still a matter of debate...."

questions questions ........

why are these receptors there ? , what function are they performing ?, are these 'other' tissues affected by having either high /or supressed TSH ? ...

[helvella Administrator in reply to tattybogle]

I think the key question is whether these other TSH receptors have any impact when TSH levels in the lower reference area - something like 0.4 to 1.5?

Or do they only come into play with higher TSH - say, above typical reference intervals?

Given the number who manage with effectively no TSH - often for many years - does anything go wrong, or not work, directly due to lack of TSH?

And, of course, other than all the questions and issues re Thyroid Eye Disease, do TSH receptor antibodies have effects that have never really been identified and discussed?

[arTistapple in reply to helvella]

Well helvella I do not doubt that “effects that have never really been identified and discussed?” Not to rubbish some excellent researchers around at the moment but there are quite a few influential, not so excellent people around. Much more straightforward issues are suppressed. I think this might be destined for ‘further research’. Fascinating as it is. Thanks for bringing it to our notice.

[Hashiboy]

That’s really fascinating.

[FallingInReverse]

The small intestine has been shown to be an extra-pituitary site of TSH (thyroid stimulating hormone) production.

Tissues other than the pituitary are known to be capable of producing TSH.

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