Gagnon RS 2- Thyroid Hormone Signaling, Mechanisms and Drugs

Question 1

What is thyrotoxicosis

Answer 1

Disease caused by excess thyroid hormone (Graves disease, hyperthyroidism)

Question 2

What is a highly expressed thyroid receptor in neurons? What can happen if there are mutations in this receptor?

Answer 2

Monocarboxylate transporter (MCT8) is highly expressed in neuronal tissue. Mutations in this cause thyroid hormone cell-membrane transporter defect (THCMTD) which leads to a severe and incapacitating neurological phenotype

Question 3

What is the activity and half-life of T4 like in comparison to T3?

Answer 3

T4 is a prohormone of T3 with a longer half life and lower activity.

Question 4

What must happen for thyroid hormone receptor to modulate gene expression?

Answer 4

The receptor must dimerize

Question 5

What types of co-factors complexes are involved in DNA transcription? What is their mechanisms of action?

Answer 5

Thyroid activation of DNA transcription has co-activators, which repress transcription and recruit histone de-acetylases and co-activators, which activate transcription and recruit histone acetylases

Question 6

Can thyroid hormone receptor cause effects without thyroid hormone? If so, how/what changes happen?

Answer 6

Thyroid receptor can act on the nucleus with or without thyroid hormone. When it is unliganded, it acts on the same genes it would if it were liganded, just with an opposite effect.

Note: T3 promotes energy consumption, vascularization, anti-oxidation and neural migration, all of which are necessary for the developing brain.

Question 7

What are the classes of drugs that alter thyroid hormone metabolism?

Answer 7

TH analogs
TH level modulators
TH absorption inhibitors
Synthesis and secretion of thyroid hormone
Thyroid hormone metabolism
Serum transport modulators