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08:33
An Ex vivo Culture System to Study Thyroid Development
Published on: June 6, 2014
Pituitary-thyroid setpoint and thyrotropin receptor expression in consomic rats
Lars C Moeller1, Manuela Alonso, Xiaohui Liao
1Department of Medicine, The University of Chicago, Chicago, IL 60637, USA.
Endocrinology
|July 21, 2007
Summary
Differences in thyroid-stimulating hormone (TSH) sensitivity between rat strains were investigated. Reduced thyroid sensitivity in Brown Norwegian rats is linked to lower TSH receptor (TSHR) expression, impacting TSH levels.
Area of Science:
- Endocrinology
- Genetics
- Physiology
Background:
- Thyroid-stimulating hormone (TSH) regulates thyroid hormone production.
- Genetic factors influence variations in TSH sensitivity and TSH levels between rat strains.
- Consomic rats are valuable tools for mapping quantitative trait loci.
Purpose of the Study:
- To investigate the genetic basis of differential TSH sensitivity between Dahl salt-sensitive (SS) and Brown Norwegian (BN) rat strains.
- To identify the molecular mechanisms underlying TSH level variations in these rat strains.
Main Methods:
- Utilized consomic rats (SSBN6, SSBN2) to map genetic loci influencing TSH levels.
- Assessed in vitro TSH bioactivity and in vivo physiological response to bovine TSH (bTSH).
- Sequenced the TSH receptor (TSHR) coding region and quantified TSHR mRNA and protein expression via real-time PCR and Western blot.
Main Results:
- BN rats exhibited higher serum TSH levels and reduced T4 response to bTSH compared to SS rats, indicating lower thyrocyte sensitivity.
- A specific TSHR amino acid substitution (Q46R) in BN rats was found unlikely to cause the observed differences.
- BN rats showed significantly lower TSHR mRNA and protein expression (54% of SS levels) in thyroid tissue.
Conclusions:
- The higher TSH level in BN rats is an adaptive response to reduced thyrocyte sensitivity caused by decreased TSHR expression.
- Reduced TSHR expression, not altered TSH bioactivity or TSHR structure, underlies the observed strain differences.
- These rat strains provide a model for studying genetic regulation of TSHR expression and feedback loop adjustments.
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