PMID- 34020531
OWN - NLM
STAT- MEDLINE
DCOM- 20211126
LR  - 20211126
IS  - 1336-0329 (Electronic)
IS  - 1210-0668 (Linking)
VI  - 55
IP  - 2
DP  - 2021 May 21
TI  - Thyroid hormone and thyroid hormone nuclear receptors: History and present state 
      of art.
PG  - 103-119
LID - 10.2478/enr-2021-0012 [doi]
AB  - The present review traces the road leading to discovery of L-thyroxine, thyroid 
      hormone (3,5,3 -triiodo-L-thyronine, T(3)) and its cognate nuclear receptors. 
      Thyroid hormone is a pleio-tropic regulator of growth, differentiation, and 
      tissue homeostasis in higher organisms. The major site of the thyroid hormone 
      action is predominantly a cell nucleus. T(3) specific binding sites in the cell 
      nuclei have opened a new era in the field of the thyroid hormone receptors (TRs) 
      discovery. T(3) actions are mediated by high affinity nuclear TRs, TRalpha and 
      TRbeta, which function as T(3)-activated transcription factors playing an 
      essential role as transcription-modulating proteins affecting the transcriptional 
      responses in target genes. Discovery and characterization of nuclear retinoid X 
      receptors (RXRs), which form with TRs a heterodimer RXR/TR, positioned RXRs at 
      the epicenter of molecular endocrinology. Transcriptional control via nuclear 
      RXR/TR heterodimer represents a direct action of thyroid hormone. T(3) plays a 
      crucial role in the development of brain, it exerts significant effects on the 
      cardiovascular system, skeletal muscle contractile function, bone development and 
      growth, both female and male reproductive systems, and skin. It plays an 
      important role in maintaining the hepatic, kidney and intestine homeostasis and 
      in pancreas, it stimulates the beta-cell proliferation and survival. The TRs 
      cross-talk with other signaling pathways intensifies the T(3) action at cellular 
      level. The role of thyroid hormone in human cancers, acting via its cognate 
      nuclear receptors, has not been fully elucidated yet. This review is aimed to 
      describe the history of T(3) receptors, starting from discovery of T3 binding 
      sites in the cell nuclei to revelation of T(3) receptors as T(3)-inducible 
      transcription factors in relation to T(3) action at cellular level. It also 
      focuses on milestones of investigation, comprising RXR/TR dimerization, 
      cross-talk between T(3) receptors, and other regulatory pathways within the cell 
      and mainly on genomic action of T(3). This review also focuses on novel 
      directions of investigation on relationships between T(3) receptors and cancer. 
      Based on the update of available literature and the author's experimental 
      experience, it is devoted to clinicians and medical students.
CI  - (c) 2021 Julius Brtko, published by Sciendo.
FAU - Brtko, Julius
AU  - Brtko J
AD  - Institute of Experimental Endocrinology, Biomedical Research Center, Slovak 
      Academy of Sciences, Bratislava, Slovakia.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210521
PL  - Germany
TA  - Endocr Regul
JT  - Endocrine regulations
JID - 9112018
RN  - 0 (Receptors, Thyroid Hormone)
RN  - 0 (Retinoid X Receptors)
RN  - 06LU7C9H1V (Triiodothyronine)
SB  - IM
MH  - Humans
MH  - Receptors, Thyroid Hormone/*metabolism
MH  - Retinoid X Receptors/*metabolism
MH  - Triiodothyronine/*physiology
OTO - NOTNLM
OT  - gene expression
OT  - molecular mechanism of action
OT  - nuclear thyroid hormone receptor
OT  - retinoid X receptor
OT  - thyroid hormone
OT  - thyroid hormone-inducible transcription factor
EDAT- 2021/05/22 06:00
MHDA- 2021/11/27 06:00
CRDT- 2021/05/21 20:34
PHST- 2021/05/21 20:34 [entrez]
PHST- 2021/05/22 06:00 [pubmed]
PHST- 2021/11/27 06:00 [medline]
AID - enr-2021-0012 [pii]
AID - 10.2478/enr-2021-0012 [doi]
PST - epublish
SO  - Endocr Regul. 2021 May 21;55(2):103-119. doi: 10.2478/enr-2021-0012.