Type 2 iodothyronine deiodinase in skeletal muscle: effects of hypothyroidism and fasting.
BACKGROUND
The iodothyronine deiodinases D1, D2, and D3 enable tissue-specific adaptation of thyroid hormone levels in response to various conditions, such as hypothyroidism or fasting. The possible expression of D2 mRNA in skeletal muscle is intriguing because this enzyme could play a role in systemic as well as local T3 production.


OBJECTIVE
We determined D2 activity and D2 mRNA expression in human skeletal muscle biopsies under control conditions and during hypothyroidism, fasting, and hyperinsulinemia.


METHODS
This was a prospective study.


METHODS
The study was conducted at a university hospital.


METHODS
We studied 11 thyroidectomized patients with differentiated thyroid carcinoma (DTC) on and after 4 wk off T4( replacement and six healthy lean subjects in the fasting state and during hyperinsulinemia after both 14 and 62 h of fasting.


METHODS
D2 activity and D2 mRNA levels were measured in skeletal muscle samples.


RESULTS
No differences were observed in muscle D2 mRNA levels in DTC patients on and off T4 replacement therapy. In healthy subjects, muscle D2 mRNA levels were lower after 62 h compared to 14 h of fasting. Insulin increased mRNA expression after 62 h, but not after 14 h of fasting. Skeletal muscle D2 activities were very low and not influenced by hypothyroidism and fasting.


CONCLUSIONS
Human skeletal muscle D2 mRNA expression is modulated by fasting and insulin, but not by hypothyroidism. The lack of a clear effect of D2 mRNA modulation on the observed low D2 activities questions the physiological relevance of D2 activity in human skeletal muscle.
Heemstra
Karen A
KA
Leiden University Medical Centre, Department of Endocrinology and Metabolic Diseases, P.O. Box 9600, Leiden 2300 RC, The Netherlands. k.a.heemstra@lumc.nl
Soeters
Maarten R
MR
Fliers
Eric
E
Serlie
Mireille J
MJ
Burggraaf
Jacobus
J
van Doorn
Martijn B
MB
van der Klaauw
Agatha A
AA
Romijn
Johannes A
JA
Smit
Johannes W
JW
Corssmit
Eleonora P
EP
Visser
Theo J
TJ
D002277:Carcinoma / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000601:surgery; D005215:Fasting / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D020249:Hormone Replacement Therapy; D006801:Humans; D007037:Hypothyroidism / Q000209:etiology / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D008012:Lidocaine / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000201:enzymology / Q000378:metabolism*; D013963:Thyroid Hormones / Q000627:therapeutic use; D013964:Thyroid Neoplasms / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000601:surgery; D013965:Thyroidectomy / Q000009:adverse effects / Q000534:rehabilitation; D000097564:Iodothyronine Deiodinase Type II
D007328:Insulin; D007453:Iodide Peroxidase; D008012:Lidocaine; D013963:Thyroid Hormones; D000097564:Iodothyronine Deiodinase Type II