Genomic and non-genomic mechanisms of action of thyroid hormones and their catabolite 3,5-diiodo-l-thyronine in Mammals

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Since the realization that the cellular homologs of a gene found in the retrovirus thatcontributes to erythroblastosis in birds (v-erbA), i.e. the proto-oncogene c-erbA encodes the nuclearreceptors for thyroid hormones (THs), most of the interest for THs focalized on their ability tocontrol gene transcription. It was found, indeed, that, by regulating gene expression in many tissues,these hormones could mediate critical events both in development and in adult organisms. Amongtheir eects, much attention was given to their ability to increase energy expenditure, and they wereearly proposed as anti-obesity drugs. However, their clinical use has been strongly challenged by theconcomitant onset of toxic eects, especially on the heart. Notably, it has been clearly demonstratedthat, besides their direct action on transcription (genomic eects), THs also have non-genomic eects,mediated by cell membrane and/or mitochondrial binding sites, and sometimes triggered by theirendogenous catabolites. Among these latter molecules, 3,5-diiodo-L-thyronine (3,5-T2) has beenattracting increasing interest because some of its metabolic eects are similar to those induced byT3, but it seems to be safer. The main target of 3,5-T2 appears to be the mitochondria, and it hasbeen hypothesized that, by acting mainly on mitochondrial function and oxidative stress, 3,5-T2might prevent and revert tissue damages and hepatic steatosis induced by a hyper-lipid diet, whileconcomitantly reducing the circulating levels of low density lipoproteins (LDL) and triglycerides.Besides a summary concerning general metabolism of THs, as well as their genomic and non-genomiceects, herein we will discuss resistance to THs and the possible mechanisms of action of 3,5-T2,also in relation to its possible clinical use as a drug.
Lingua originaleEnglish
pagine (da-a)1-40
Numero di pagine40
RivistaInternational Journal of Molecular Sciences
Stato di pubblicazionePublished - 2020

All Science Journal Classification (ASJC) codes

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  • ???subjectarea.asjc.1300.1312???
  • ???subjectarea.asjc.1600.1607???
  • ???subjectarea.asjc.1700.1706???
  • ???subjectarea.asjc.1600.1606???
  • ???subjectarea.asjc.1600.1605???
  • ???subjectarea.asjc.1600.1604???


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