Tanycytes control the hormonal output of the hypothalamic-pituitary-thyroid axis

[helvella]

On this forum, as in much of the world of thyroid, we discuss thyroid hormones, the thyroid, the pituitary, iron, vitamins, and goodness knows what else. We almost never mention the hypothalamus.

That is why I am posting this abstract. Not that I more than slightly understand it! But we should never forget the hypothalamus, TRH (Thyrotropin-releasing hormone) and the impact of that on the pituitary.

Nat Commun. 2017 Sep 7;8(1):484. doi: 10.1038/s41467-017-00604-6.

Tanycytes control the hormonal output of the hypothalamic-pituitary-thyroid axis.

Müller-Fielitz H1, Stahr M2, Bernau M2, Richter M2, Abele S2, Krajka V2, Benzin A2, Wenzel J2, Kalies K3, Mittag J4, Heuer H5, Offermanns S6, Schwaninger M7.

Author information

1 Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany. [e-mail].

2 Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.

3 Institute of Anatomy, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.

4 Department of Internal Medicine, Molecular Endocrinology, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany.

5 Leibniz Research Institute for Environmental Medicine, Auf'm Hennekamp 50, 40225, Düsseldorf, Germany.

6 Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, Ludwigstraße 43, 61231, Bad Nauheim, Germany.

7 Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, 23562, Lübeck, Germany. [e-mail].

Abstract

The hypothalamic-pituitary-thyroid (HPT) axis maintains circulating thyroid hormone levels in a narrow physiological range. As axons containing thyrotropin-releasing hormone (TRH) terminate on hypothalamic tanycytes, these specialized glial cells have been suggested to influence the activity of the HPT axis, but their exact role remained enigmatic. Here, we demonstrate that stimulation of the TRH receptor 1 increases intracellular calcium in tanycytes of the median eminence via Gαq/11 proteins. Activation of Gαq/11 pathways increases the size of tanycyte endfeet that shield pituitary vessels and induces the activity of the TRH-degrading ectoenzyme. Both mechanisms may limit the TRH release to the pituitary. Indeed, blocking TRH signaling in tanycytes by deleting Gαq/11 proteins in vivo enhances the response of the HPT axis to the chemogenetic activation of TRH neurons. In conclusion, we identify new TRH- and Gαq/11-dependent mechanisms in the median eminence by which tanycytes control the activity of the HPT axis. The hypothalamic-pituitary-thyroid (HPT) axis regulates a wide range of physiological processes. Here the authors show that hypothalamic tanycytes play a role in the homeostatic regulation of the HPT axis; activation of TRH signaling in tanycytes elevates their intracellular Ca2+ via Gαq/11 pathway, ultimately resulting in reduced TRH release into the pituitary vessels.

PMID: 28883467

DOI: 10.1038/s41467-017-00604-6

ncbi.nlm.nih.gov/pubmed/288...

[BadHare]

Thanks Helvella!

I'm aware that TRH is what should be tested for secondary, & possibly tertiary hypothyroidism, rather than TSH. This seems to be something else the endocrinologists don't seem to be aware of as it's not done here.

[helvella Administrator in reply to BadHare]

I don't think it is done anywhere!

[BadHare in reply to helvella]

Silly when it's not an uncommon illness, & extremely frustrating to be told my TSH is "normal"!

[helvella Administrator in reply to BadHare]

I'll take back my response a moment ago - it is done sometimes, even in the UK, but have a read of this:

Thyrotropin releasing hormone (TRH) test

Indication

The development of TSH assays capable of accurate measurements below 0.1 mU/L has obviated the need for the TRH test in most cases of thyroid practice except perhaps in the differential diagnosis of TSHoma and thyroid hormone resistance (high TSH and high thyroxine).

pathology.leedsth.nhs.uk/dn...

Edit:

This is the TRH Stimulation Test! My mistake.

[BadHare in reply to helvella]

One I found:

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

Abstract

Hypothyroidism is divided in primary, caused by failure of thyroid function and secondary (central) due to the failure of adequate thyroid-stimulating hormone (TSH) secretion from the pituitary gland or thyrotrophin-releasing hormone (TRH) from the hypothalamus. Secondary hypothyroidism can be differentiated in pituitary and hypothalamic by the use of TRH test...

[helvella Administrator in reply to BadHare]

And this has some interest:

eurospe.org/clinical/CPC%20...

[BadHare in reply to helvella]

I think I read this, & some other articles from Leeds when I was loking for help 4 years ago.

[Justiina in reply to helvella]

I wish I could find article that says that secretion of TSH is not "stable". Pituitary can hold loads of TSH without releasing it or only release a bit even though one would be very hypo. Can't remember why. But it was underlined that TRH should be done routinely in certain cases as TSH test fails for these people.

[jimh111]

The axis is important, I see quite a few patients on these forums who have low-normal TSH, fT3, fT4. Many tissues are able to convert T4 to T3 and so they respond to the combined effects of T3 plus T4. A mildly low TRH means the TSH fails to elevate. The reduced TSH fails to stimulate extra type-2 deiodinase. I believe these patients need some T3 medication to compensate for these effects.

A sub-normal axis can be caused by depression, strict dieting or a down-regulated axis arising from a period of hyperthyroidism. This possibility is not considered by doctors.

[SlowDragon Administrator]

Is it possible to get a TRH blood test privately.

If not perhaps this is something Blue Horizon and Medichecks could consider offering

[helvella Administrator in reply to SlowDragon]

I mistakenly linked to a Leeds Pathology page about TRH testing earlier - but that is actually the TRH Stimulation test.

There is a direct TRH test described here:

questdiagnostics.com/testce...

Need for special collection tube, fast separation followed by immediate freezing, seems to make it an unlikely candidate for any form of remote testing. It must be done in a unit with separation and freezing facilities - even if actual analysis were to be done remotely.

[SlowDragon Administrator in reply to helvella]

Very unlikely then - parathyroid also requires quick testing so difficult privately