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Salivary gland hypofunction in tyrosylprotein sulfotransferase-2 knockout mice is due to primary hypothyroidism.
- Source :
-
PloS one [PLoS One] 2013 Aug 07; Vol. 8 (8), pp. e71822. Date of Electronic Publication: 2013 Aug 07 (Print Publication: 2013). - Publication Year :
- 2013
-
Abstract
- Background: Protein-tyrosine sulfation is a post-translational modification of an unknown number of secreted and membrane proteins mediated by two known Golgi tyrosylprotein sulfotransferases (TPST-1 and TPST-2). We reported that Tpst2-/- mice have mild-moderate primary hypothyroidism, whereas Tpst1-/- mice are euthyroid. While using magnetic resonance imaging (MRI) to look at the thyroid gland we noticed that the salivary glands in Tpst2-/- mice appeared smaller than in wild type mice. This prompted a detailed analysis to compare salivary gland structure and function in wild type, Tpst1-/-, and Tpst2 -/- mice.<br />Methodology/principal Findings: Quantitative MRI imaging documented that salivary glands in Tpst2-/- females were (≈) 30% smaller than wild type or Tpst1-/- mice and that the granular convoluted tubules in Tpst2-/- submandibular glands were less prominent and were almost completely devoid of exocrine secretory granules compared to glands from wild type or Tpst1-/- mice. In addition, pilocarpine-induced salivary flow and salivary α-amylase activity in Tpst2-/- mice of both sexes was substantially lower than in wild type and Tpst1-/- mice. Anti-sulfotyrosine Western blots of salivary gland extracts and saliva showed no differences between wild type, Tpst1-/-, and Tpst2-/- mice, suggesting that the salivary gland hypofunction is due to factor(s) extrinsic to the salivary glands. Finally, we found that all indicators of hypothyroidism (serum T4, body weight) and salivary gland hypofunction (salivary flow, salivary α-amylase activity, histological changes) were restored to normal or near normal by thyroid hormone supplementation.<br />Conclusions/significance: Our findings conclusively demonstrate that low body weight and salivary gland hypofunction in Tpst2-/- mice is due solely to primary hypothyroidism.
- Subjects :
- Animals
Blotting, Western
Body Weight drug effects
Body Weight genetics
Body Weight physiology
Dietary Supplements
Female
Gene Expression
Hypothyroidism blood
Hypothyroidism genetics
Magnetic Resonance Imaging
Male
Mice
Mice, 129 Strain
Mice, Knockout
Reverse Transcriptase Polymerase Chain Reaction
Salivary Glands pathology
Salivary Glands physiopathology
Salivary alpha-Amylases metabolism
Submandibular Gland metabolism
Submandibular Gland pathology
Submandibular Gland physiopathology
Sulfotransferases genetics
Thyroid (USP) administration & dosage
Thyroid (USP) pharmacology
Thyroxine blood
Hypothyroidism metabolism
Salivary Glands metabolism
Sulfotransferases metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 8
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 23951251
- Full Text :
- https://doi.org/10.1371/journal.pone.0071822