Thyroid function is maintained despite increased oxidative stress in mice lacking selenoprotein biosynthesis in...

Area of Science:

• Endocrinology
• Molecular Biology
• Cell Biology

Background:

• Thyroid epithelial cells synthesize thyroid hormones, a process involving hydrogen peroxide production and potential oxidative damage.
• Selenium (Se)-containing antioxidative enzymes, such as glutathione peroxidases (GPxs) and thioredoxin reductases, are expressed in thyrocytes and contain selenocysteine (Sec).
• Low Se status is linked to thyroid dysfunction, suggesting selenoproteins are crucial for thyroid health.

Purpose of the Study:

• To investigate the role of selenoproteins in protecting thyroid epithelial cells from oxidative stress.
• To determine the impact of selenoprotein deficiency on thyroid hormone biosynthesis and thyroid integrity.
• To test the hypothesis that selenoproteins are essential for thyrocyte survival.

Main Methods:

• A genetic loss-of-function approach was employed, conditionally inactivating selenoprotein biosynthesis in thyrocytes by targeting the Sec tRNA gene using Cre/loxP recombination.
• Thyroid extracts were analyzed for selenoenzyme activity (GPx, type I-deiodinase).
• Oxidative stress markers (4-hydroxynonenal, 3-nitro-tyrosine) were assessed via immunohistochemistry; thyroid morphology, circulating thyroid hormone levels, and thyrotropin (TSH) levels were monitored.

Main Results:

• Conditional inactivation of Sec tRNA significantly reduced GPx and type I-deiodinase activities in thyroid extracts.
• Increased levels of oxidative stress markers were observed in selenoprotein-deficient thyrocytes.
• Despite oxidative stress, thyroid morphology remained intact, circulating thyroid hormone levels were normal, and TSH levels were moderately elevated. Low iodine diet challenge did not cause thyroid destruction.

Conclusions:

• Selenoproteins play a protective role against oxidative damage in thyrocytes.
• These enzymes modulate thyroid hormone biosynthesis.
• Selenoproteins are not essential for the survival of thyrocytes.