Interdependence of thyroglobulin processing and thyroid hormone export in the mouse thyroid gland

Area of Science:

• Endocrinology
• Cell Biology
• Molecular Biology

Background:

• Thyroid epithelial cells must maintain adequate thyroid hormone (TH) levels for bodily functions.
• These cells produce TH and are also responsive to it, indicating a need for auto-regulatory mechanisms.
• The precise cellular pathways governing thyroid auto-regulation remain incompletely understood.

Purpose of the Study:

• To investigate if thyroglobulin processing and TH export are sensed by thyrocytes.
• To explore the relationship between thyroglobulin processing and TH transporter levels.
• To elucidate molecular pathways involved in thyroid auto-regulation.

Main Methods:

• Inactivation of thyroglobulin-processing cathepsins and TH-exporting monocarboxylate transporters (Mct) in mice.
• Immunoblotting and immunofluorescence microscopy to analyze thyroglobulin, cathepsins, and Mct protein levels.
• Examination of endo-lysosomal compartments in thyroid epithelial cells.

Main Results:

• Cathepsin-deficient mice exhibited increased Mct8 protein levels at the basolateral membrane.
• Mct8/Mct10 double deficiency led to increased levels of cathepsins B and L.
• Mct8- and/or Mct10-deficient cells showed larger endo-lysosomes containing cathepsins B, D, and L.

Conclusions:

• A crosstalk exists between TH transporters and thyroglobulin-processing proteases in thyroid epithelial cells.
• Defective TH export positively influences cathepsin-mediated thyroglobulin processing, potentially causing auto-toxic states.
• These findings suggest the presence of TH-sensing molecules within thyrocytes that contribute to thyroid auto-regulation.