[Thyroid hormones and muscle phenotype: involvement of new signaling pathways].
Thyroid hormones (TH) are known to control development, body and muscle growth, as well as to determine muscle phenotype in the adult. TH affect muscle properties through nuclear receptors; they act either by a positive or a negative control on target genes that encode proteins accounting for contractile or metabolic phenotypes. Contractile activity and muscle load also affect muscle phenotype; several intracellular signaling pathways are involved in the transduction of signals related to contractile activity, including the calcineurin/NFAT pathway. Calcineurin activity is negatively controlled by MCIP-1 protein (modulatory calcineurin-interacting protein-1). We recently performed an experiment aimed at examining the specific and combined effects of the pharmacological calcineurin inhibition (using cyclosporin-A CsA administration) and thyroid hormone deficiency. The expected effects of CsA administration were only observed if TH were available, while thyroid deficiency totally blunted the muscle responses to calcineurin inhibition. In conditions of thyroid hormone deficiency, there was no response to the pharmacological inhibition of calcineurin, usually known to induce a slow-to-fast IIA transition associated with an enhancement of mitochondrial biogenesis in normothyroid rats. Moreover, thyroid deficiency markedly decreased the expression of MCIP-1 and MCIP-2 mRNA and proteins, two endogenous calcineurin inhibitors; such results clearly suggest that thyroid hormone and calcineurin pathways are interconnected.
Bigard
André-Xavier
AX
Département des facteurs humains, centre de recherche du service de santé des armées, BP 87, 38702 La Tronche Cedex, France. xbigard@crssa.net
Koulmann
Nathalie
N
Bahi
Lahoucine
L
Sanchez
Hervé
H
Ventura-Clapier
Renée
R
D000818:Animals; D019703:Calcineurin / Q000502:physiology; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000494:pharmacology; D004268:DNA-Binding Proteins; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D009119:Muscle Contraction; D024510:Muscle Development; D009124:Muscle Proteins / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*; D050778:NFATC Transcription Factors / Q000502:physiology; D010641:Phenotype; D015398:Signal Transduction / Q000502:physiology*; D013963:Thyroid Hormones / Q000172:deficiency / Q000502:physiology*
D065095:Calcineurin Inhibitors; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D050778:NFATC Transcription Factors; C108612:RCAN1 protein, human; C100360:RCAN2 protein, human; D013963:Thyroid Hormones; D016572:Cyclosporine; D019703:Calcineurin