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Updated: Sep 22, 2026

Diagnostic Ultrasound Imaging of Mouse Diaphragm Function
Published on: April 21, 2014
Hypothyroidism alters diaphragm muscle development
G C Sieck1, L E Wilson, B D Johnson
1Department of Anesthesiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. gcs@Siecklab.Mayo.edu
Insights
Hypothyroidism in developing rats alters myosin heavy chain (MHC) expression in diaphragm muscles, leading to reduced muscle force and slower shortening velocity. These changes in MHC isoforms do not fully explain the observed alterations in diaphragm contractile properties.
Area of Science:
- Physiology
- Developmental Biology
- Endocrinology
Background:
- Hypothyroidism affects muscle development and function.
- Myosin heavy chain (MHC) isoforms are critical for muscle contractility.
- Understanding these impacts during development is crucial for pediatric endocrinology and muscle physiology.
Purpose of the Study:
- To investigate the effects of hypothyroidism on rat diaphragm muscle (Dia) MHC isoform expression, force production, fatigability, and shortening velocity during postnatal development.
- To determine if changes in MHC isoform expression correlate with alterations in diaphragm contractile function.
Main Methods:
- Hypothyroidism induced in pregnant rats using propyl-thiouracil.
- Analysis of MHC isoforms in diaphragm muscle via SDS-PAGE and densitometry.
- In vitro assessment of isometric force, fatigue resistance, and unloaded shortening velocity of the diaphragm.
Main Results:
- Hypothyroid diaphragm muscles showed increased MHC-slow and decreased adult fast MHC isoform expression.
- Neonatal MHC isoform expression persisted in hypothyroid muscles until day 28.
- Reduced maximum specific force (P0), increased fatigability, and slower maximum unloaded shortening velocity (V0) were observed in hypothyroid diaphragm muscles at all ages.
- Hypothyroidism-induced changes in MHC isoform expression did not fully account for the observed deficits in diaphragm contractile properties.
Conclusions:
- Hypothyroidism significantly alters MHC isoform composition and contractile function in the developing rat diaphragm.
- The relationship between MHC isoform expression and diaphragm contractile properties is complex and not fully explained by isoform shifts alone.
- Further research is needed to elucidate the mechanisms underlying hypothyroid myopathy in developing skeletal muscle.
Abstract:
The impact of hypothyroidism (Hyp) on myosin heavy chain (MHC) isoform expression, maximum specific force (P0), fatigability, and maximum unloaded shortening velocity (V0) was determined in the rat diaphragm muscle (Dia) at 0, 7, 14, 21, and 28 days of age. Hyp was induced by treating pregnant rats with 6-n-propyl-2-thiouracil (0.05% in drinking water) beginning at gestational day 10 and was confirmed by reduced plasma levels of 3,5,3'-triiodothyronine and thyroxine. MHC isoforms were separated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels and analyzed by densitometry. Isometric P0 and fatigue resistance of the Dia were measured in vitro at 26 degrees C, and V0 was determined at 15 degrees C with the slack test. Compared with control muscles, expression of MHC-slow was higher and expression of adult fast MHC isoforms was lower in Hyp Dia at all ages. The neonatal isoform of MHC continued to be expressed in the Hyp Dia until day 28. At each age, P0 and fatigability were reduced and V0 was slower in the Hyp Dia. We conclude that Hyp-induced alterations in MHC isoform expression do not fully predict the changes in Dia contractile properties.
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