We have long seen disagreement about the association between thyroid hormone levels and cholesterol levels. All too often any association is dismissed - partly due to lack of any proved mechanism.
This paper suggests a mechanism by which TSH could directly affect cholesterol levels - not due to any effect of thyroid hormones. This could, obviously, suggest that leaving TSH to rise to 10 or higher might itself cause cholesterol to rise. And that treatment with thyroid hormone, to reduce TSH, might be a sensible treatment for excessive cholesterol. (Let us not for one moment suggest that the thyroid hormones might themselves be beneficial, o no, that is far too radical.)
The paper goes off on a different tangent - a medicine that might block the TSH receptor and stop it having this effect. Understandable, and possibly useful when the person cannot tolerate levels of thyroid hormone required to reduce TSH sufficiently (if any exist).
First Published on February 23, 2015, doi: 10.1194/jlr.M047654
The Journal of Lipid Research,
jlr.M047654.
Thyroid-Stimulating Hormone Decreases HMG-CoA Reductase Phosphorylation via AMP-Activated Protein Kinase in the liver
Xiujuan Zhang1,
Yongfeng Song1,
Mei Feng1,
Xinli Zhou1,
Ling Gao1,
Chunxiao Yu2,
Xiuyun Jiang1 and
Jiajun Zhao1,*
1 Shandong Provincial Hospital Affiliated to Shandong University, China;
2 Shandong Academy of Clinical Medicine, China
↵* Corresponding author; email: jjzhao{at}medmail.com.cn
Abstract
Cholesterol homeostasis is strictly regulated through the modulation of HMG-CoA Reductase (HMGCR), the rate-limiting enzyme of cholesterol synthesis. Phosphorylation of HMGCR inactivates and dephosphorylation activates it. AMPK is the major kinase phosphorylating the enzyme. Our previous study found that thyroid-stimulating hormone (TSH) increased the hepatocytic HMGCR expression, but it was still unclear if TSH affected hepatic HMGCR phosphorylation associated with AMPK. We used bTSH to treat the primary mouse hepatocytes and HepG2 cells with or without CA-AMPK plasmid or protein kinase A inhibitor (H89), and set up the TSH receptor (Tshr)-knockout mouse models. The p-HMGCR, p-AMPK and related molecular expression were tested. The ratios of p-HMGCR/HMGCR and p-AMPK/AMPK decreased in the hepatocytes in a dose-dependent manner following bTSH stimulation. The changes above were inversed when the cells were treated with CA-AMPK plasmid or H89. In Tshr-knockout mice, the ratios of liver p-HMGCR/HMGCR and p-AMPK/AMPK were increased relative to the littermate wild-type mice. Consistently, the phosphorylation of ACC, a downstream target molecular of AMPK, increased. All results suggested that TSH could regulate the phosphorylation of HMGCR via AMPK, which established a potential mechanism for hypercholesterolemia involved in a direct action of the TSH in liver.
Cholesterol
Enzymology/Enzyme mechanisms
Liver
Protein kinases/AMP-activated protein kinase
Receptors/Hormone
HMG-CoA rerductase
TSH
Received January 28, 2014.
Accepted February 23, 2015.
jlr.org/content/early/2015/...
Happily, the abstract and full paper (as web pages or as PDF) all freely available from links on that page. 
Rod
