Thyroid Hormone Deiodinases: Dynamic Switches in Developmental Transitions

[helvella]

We keep getting hints of how thyroid hormones are managed, how they work, and the range of impacts they have. Not just the thyroid hormones, but also the deiodinases which are so fundamental.

Endocrinology

. 2021 May 8;bqab091.

doi: 10.1210/endocr/bqab091. Online ahead of print.

Thyroid Hormone Deiodinases: Dynamic Switches in Developmental Transitions

Arturo Hernandez 1 2 3 , M Elena Martinez 1 , Lily Ng 4 , Douglas Forrest 4

• PMID: 33963379

• DOI: 10.1210/endocr/bqab091

Abstract

Thyroid hormones exert pleiotropic, essential actions in mammalian, including human, development. These actions depend upon provision of thyroid hormones in the circulation but also to a remarkable extent upon deiodinase enzymes in target tissues that amplify or deplete the local concentration of the primary active form of the hormone T3 (3,5,3'-triiodothyronine), the high affinity ligand for thyroid hormone receptors. Genetic analyses in mice have revealed key roles for activating (DIO2) and inactivating (DIO3) deiodinases in cell differentiation fates and tissue maturation, ultimately promoting neonatal viability, growth, fertility, brain development and behavior, as well as metabolic, endocrine and sensory functions. An emerging paradigm is how the opposing activities of DIO2 and DIO3 are coordinated, providing a dynamic switch that controls the developmental timing of a tissue response, often during neonatal and maturational transitions. A second paradigm is how cell-cell communication within a tissue determines the response to T3. Deiodinases in specific cell types, often strategically located near to blood vessels that convey thyroid hormones into the tissue, can regulate neighboring cell types, suggesting a paracrine-like layer of control of T3 action. We discuss deiodinases as switches for developmental transitions and their potential to influence tissue dysfunction in human thyroid disorders.

Keywords: Deiodinase; central nervous system; development; neuroendocrine function; sensory system; thyroid hormone.

Rest of paper is, as so often, behind a paywall:

pubmed.ncbi.nlm.nih.gov/339...

Pleiotropy (from Greek πλείων pleion, "more", and τρόπος tropos, "way") occurs when one gene influences two or more seemingly unrelated phenotypic traits. Such a gene that exhibits multiple phenotypic expression is called a pleiotropic gene. Mutation in a pleiotropic gene may have an effect on several traits simultaneously, due to the gene coding for a product used by a myriad of cells or different targets that have the same signaling function.

en.wikipedia.org/wiki/Pleio...

Paracrine signaling is form of cell signaling, a type of cellular communication in which a cell produces a signal to induce changes in nearby cells, altering the behaviour of those cells. Signaling molecules known as paracrine factors diffuse over a relatively short distance (local action), as opposed to cell signaling by endocrine factors, hormones which travel considerably longer distances via the circulatory system; juxtacrine interactions; and autocrine signaling. Cells that produce paracrine factors secrete them into the immediate extracellular environment. Factors then travel to nearby cells in which the gradient of factor received determines the outcome. However, the exact distance that paracrine factors can travel is not certain.

en.wikipedia.org/wiki/Parac...

[tattybogle]

Good find , thanks for the help in translation

[janeroar]

Thanks Helvella though it’s still over my head even with some translation from you!

[helvella Administrator Thyroid UK in reply to janeroar]

It's very simple, really. It is very complex and no-one understands it all!

Most importantly, those who act as if they do understand it all, think very much of some endocrinologists who do a bit of thyroid on the side, have a tendency to demonstrate their ignorance by treating it all as something they do understand fully and yet saying and doing things which contradict that.

[tattybogle in reply to helvella]

Too true ... imagine having an appointment where they said ," well i wasn't expecting your bloods to do that in response to 'x' ... how curious .i don't understand , but i wonder why .... how do you feel ? " I would have sooo much more respect for someone who said that, than . 'are you sure you've been taking the tablets '

[Jacs in reply to tattybogle]

🤣