Translation of Thyroid Hormone Actions beyond Classical Concepts

[Justiina]

Research in Germany. Browse Publications to see what they have discovered so far.

thyroidtransact.de

[helvella Administrator Thyroid UK]

I liked the front page statements!

Also, for those who have come across Milk Thistle (and extracts) for liver issues:

Silychristin, a Flavonolignan Derived From the Milk Thistle, Is a Potent Inhibitor of the Thyroid Hormone Transporter MCT8

The article was published in Endocrinology 2016, Volume 157, Issue 4. Jörg Johannes and Kostja Renko summarizes the main statements.

Bad news for the hepatoprotective “over-the-counter”-drug Silymarine? Recent in vitro results from the “Institut für Experimentelle Endokrinologie”, published in the scientific journal “Endocrinology”, raise the suspicion that this frequently used extract preparation from Milk Thistle (Mariendistel), a popular plant in folk medicine, might interfere with the function of the Monocarboxylate transporter 8 (MCT8) (1). MCT8 is the most important human thyroid hormone transporter and thus a potential target for endocrine active compounds (EAC). The disastrous consequences of MCT8 malfunction are well studied, and its genetic inactivation provokes a severe neurological phenotype, referred as Allan-Herndon-Dudley syndrome (AHDS) (2,3).

By a screening approach, using a recently developed assay to identify MCT8-inhibitors (4), the authors tested compounds from a preselected EAC library. Silymarin, the Milk Thistle extract in a final concentration of 10 µM, reduced MCT8-related T3 transport. Since silymarin is a complex mixture of flavonolignans, they further tested its individual components and identified Silychristin as its active ingredient which is at least one order of magnitude more potent (IC50 ~ 100 nM) than other known thyroid hormone transporter inhibitors. This finding was confirmed in primary murine astrocytes expressing endogenous Mct8 while MCT10-overexpressing MDCK1-cells were not affected. This indicates a remarkable specificity of the inhibitor towards MCT8.

As a positive perspective in science, Silychristin could serve as a lead structure to predict thyroid hormone transporter interactions and will be a helpful and promising tool in respective studies.

Another, more negative aspect is the fact that Silymarine-containing drugs are in frequent use for their hepatoprotective attributes. A typical milk thistle extract contains Silibinin, Isosilibinin, Silichristin and Silidianin in varying shares. From the literature, Silymarin is broadly accepted as a “safe herbal dietary supplement” and considered to be well tolerated. However, many studies are using pure Silibinin because it is the main compound of Silymarin, and most positive effects are referred to it. Studies on Silibinin might therefore underestimate the potential risk of complex Silymarin extracts regarding the thyroid hormone axis. It might be speculated, that inhibition of Mct8-dependent thyroid hormone transport might contribute to the hepatoprotective action ascribed to silymarin extracts.

The data published by Johannes et al. strongly suggest attentive care on the use of this herbal drug. It raises recommendation that studies on Silymarin use and safety should include a thorough analysis of the thyroid hormone axis and a more intensive characterization of the metabolism of Silymarin and its components.

1. Johannes J, Jayarama-Naidu R, Meyer F, Wirth EK, Schweizer U, Schomburg L, Köhrle J, Renko K. Silychristin, a Flavonolignan Derived From the Milk Thistle, Is a Potent Inhibitor of the Thyroid Hormone Transporter MCT8. Endocrinology 2016;157(4):1694–1701.

2. Braun D. The importance of thyroid hormone transporters. Nuklearmedizin 2015;54(3):77–81.

3. Bernal J, Guadaño-Ferraz A, Morte B. Thyroid hormone transporters–functions and clinical implications. Nat. Rev. Endocrinol. 2015;11(7):406–417.

4. Jayarama-Naidu R, Johannes J, Meyer F, Wirth EK, Schomburg L, Köhrle J, Renko K. A Nonradioactive Uptake Assay for Rapid Analysis of Thyroid Hormone Transporter Function. Endocrinology 2015;156(7):2739–2745.

thyroidtransact.de/news/42

[Justiina in reply to helvella]

I like the statement of how expensive thyroid issues are! They have done the math!

List of upcoming research was impressive and interesting.

[SmallBlueThing]

Aortic wall thickness significantly associated with TSHes greater than 3.29 mIU/L.

ncbi.nlm.nih.gov/pubmed/269...

[Justiina in reply to SmallBlueThing]

So relatively low TSH which is still considered euthyroid for most.