Scavenger Receptor Class B Member 1 Independent Uptake of Transthyretin by Cultured Hepatocytes Is Regulated by High Density Lipoprotein

[helvella]

I really don't know where to start with this paper! Does it make any sense that T4 can be taken into cells whilst actually bound to a transporter protein (transthyretin)?

Transthyretin is also involved with vitamin A (the name comes from trans(porter) thy(roid hormone) retin(ol) - a form of vitamin A).

And then throw in the possibility of HDL (high density lipoprotein - usually discussed in relation to cholesterol) being a part of the process.

If you don't understand a word, walk on by. I can't tell you how many times I have stuttered through it myself. Still not sure what it all means but the mere possibility of this being a description of reality adds yet another level of complexity.

Journal of Lipids

Volume 2019, Article ID 7317639, 7 pages

doi.org/10.1155/2019/7317639

Research Article

Scavenger Receptor Class B Member 1 Independent Uptake of Transthyretin by Cultured Hepatocytes Is Regulated by High Density Lipoprotein

Kelly A. Landers,1 Michael C. d’Emden,2,3 and Kerry Richard

1,3,4

1 Conjoint Internal Medicine Laboratory, Chemical Pathology, Pathology Queensland, Queensland Health, Herston, QLD 4029, Australia

2Department of Endocrinology and Diabetes, Royal Brisbane and Women’s Hospital, Herston, QLD 4029, Australia

3 School of Medicine, University of Queensland, Herston, QLD 4029, Australia

4 School of Biomedical Sciences, Queensland University of Technology, Brisbane, QLD 4000, Australia

Correspondence should be addressed to Kerry Richard; [e-mail]

Received 9 April 2019; Revised 31 May 2019; Accepted 4 June 2019; Published 18 June 2019

Academic Editor: Matti Jauhiainen

Abstract

Thyroid hormone (thyroxine, T4) is essential for the normal function of all cell types and is carried in serum bound to several proteins including transthyretin. Recently, evidence has emerged of alternate pathways for hormone entry into cells that are dependent on hormone binding proteins. Transthyretin and transthyretin bound T4 are endocytosed by placental trophoblasts through the high-density lipoprotein receptor, Scavenger Receptor Class B Type 1 (SR-B1). High density lipoprotein (HDL) affects the expression and function of SR-B1 in trophoblast cells. SR-B1 is also expressed in hepatocytes and we sought to determine if hepatocyte SR-B1 was involved in transthyretin or transthyretin-T4 uptake and whether uptake was affected by HDL. Transthyretin and transthyretin-T4 uptake by hepatocytes is not dependent on SR-B1. HDL treatment reduced SR-B1 expression. However, pretreatment of hepatocytes with HDL increased uptake of transthyretin-T4. Knockdown of SR-B1 expression using siRNA also increased transthyretin-T4 uptake. Coaddition of HDL to transthyretin uptake experiments blocked both transthyretin and transthyretin-T4 uptake. Hepatocyte uptake of transthyretin-T4 uptake is influenced by, but is not dependent on, SR-B1 expression. HDL also decreases transthyretin-T4 uptake and therefore diet or drugs may interfere with this process. This suggests that multiple lipoprotein receptors may be involved in the regulation of uptake of transthyretin-T4 in a cell-type specific manner. Further study is required to understand this important process.

hindawi.com/journals/jl/201...

[Greekchick]

Out of my league, helvella! Seems theoretical to me - there is no explanation of what this means. I’m joining your club of not being able to make sense of it.

[helvella Administrator in reply to Greekchick]

Suggests to me an outside possbility that testing blood for thyroid hormones bound to each of the transporter proteins might be of interest.

[jimh111]

I'm not going to read this! Looks like an obscure study carried out by biochemists. It's a shame we don't get simple studies on important issues like finding which patient groups need T3 and how much T3 do they need.

Some clarification. Thyroid hormone transport is complex. TBG, albumin and TTR are serum transporters, they carry the hormones around the body in the blood. This study uses terms like 'cell-specific'. I don't think they are claiming TTR has a role in transporting T4 into cells. T3 and T4 are transported into cells by cellular transport proteins such as MCT8 and OATP1C1. Thus, there are serum transport proteins and cellular transport proteins. It all gets rather complicated .... Good Night.

[Treepie]

Shows how wonderful our make up is - until it goes wrong.

[SilverAvocado]

This comes make me think there are biochemists /pharmacologists out in the world who understand this and could make a lot of sense out of our more complex thyroid issues.

I have a friend who is a retired pharmacologist, and sometimes do try to pump him for information or to look things up for me. He's not very keen

[vocalEK]

I believe this is the type of study referred to as in vitro, as opposed to in vivo.

adjective & adverbBIOLOGY

(of a process) performed or taking place in a test tube, culture dish, or elsewhere outside a living organism.

Example: "in vitro fertilization"

This is a very basic type of research, the results of which might be totally unrelated to how the same treatment or process behaves in the living body. The problem is that the tested area is divorced from numerous other chemicals, processes, etc., that can affect the outcome IRL. *teen speak for "in real life"

[helvella Administrator in reply to vocalEK]

Everything in the paper might turn out not to be a good description of reality. But what this type of study can do is suggest possibilities and, maybe, show where to look and what to look at.