Endocrine Abstracts

Introduction: Mct8 is a thyroid hormone specific transporter located at the basolateral plasma membrane of thyrocytes. To investigate the significance of Mct8 to the thyroid gland while excluding peripheral effects observed in global knockout models, we used a Cre-LoxP thyroid-specific Mct8-deficient mouse model. Phenotypes of the angiofollicular unit encompassing the follicle and surrounding endothelial cells were investigated with respect to functional and morphological states.

Methods: Morphology of the thyroid follicles, endothelial cells and thyrocyte cell death were investigated using a computer-based cell biology toolbox. Indirect immunofluorescence of tissue cryo-sections and immunoblotting were used to analyse thyroglobulin status, along with expression and localisation of thyroglobulin-processing cathepsins.

Results: Morphological analysis demonstrates that the average thyroid follicle size in thyroid-specific Mct8-deficient mice is comparable to the Cre^−/− control. Epithelial extension was less in thyroid-specific-Mct8 deficiency, but not significantly. Strikingly, cell death in the thyroid-specific Mct8-deficient mice was 8.5-fold greater than observed in the control. Cathepsin B expression appeared increased 1.7-fold in the thyroid-specific Mct8 knockout in comparison to the control. Cathepsin L is only localised to certain thyrocytes around the follicle in the thyroid-specific-Mct8 deficient model; in the control, Cathepsin L is present across all thyrocytes. Initial observations of the thyroglobulin status suggest that a greater percentage of the prohormone in the thyroid-specific Mct8 knockout is cross-linked than the control.

Conclusion: Thyroid-specific Mct8 deficiency does not appear to have a great effect on follicle size or epithelial extension. However, differences associated with cathepsin expression and localisation suggests that Mct8 may be connected to expression and localisation of cathepsins B and L via an unknown mechanism. The absence of thyrocyte survival factor cathepsin L from many follicle cells might be the underlying cause of the increased cell death rate in follicles of the thyroid-specific-Mct8 deficient model.

Funded by DFG, BR1308/11-1, 2