Primary Cilium in the Human Thyrocyte: Changes in Frequency and Length in Relation to the Functional Pathology of the Thyroid Gland

Abstract

Background: Primary cilia (PC) are conserved structures in the adult thyroid gland of different mammals. We have recently described that, in humans, PC are usually present as a single copy per follicular cell emerging from the follicular cell apex into the follicular lumen. Methods: To better understand the role developed by PC in thyroid hormonogenesis, we investigated their changes in different human functional thyroid diseases (diffuse toxic hyperplasia/ Grave's disease and nodular hyperplasia/nodular goiter), in comparison with normal thyroid tissue, using immunofluorescence, morphometry and electron microscopy analyzes. Results: We found significantly decreased ciliary frequencies in both nodular hyperplasia (51.16±11.69%) and Grave's disease (44.43±23.70%) vs. normal thyroid glands (76.09±7.31%). Similarly, PC lengths were also significantly decreased in both nodular hyperplasia (2.02±0.35 µm) and Grave's disease (2.42±0.48 µm) compared to normal glands (3.93±0.90 µm). Moreover, in Grave's disease patients, hyperactive-follicle foci always showed diminished ciliary frequency and length compared to any other thyroid follicle pattern, independent of their thyroid status. Conclusions: Our results suggest a direct relationship between ciliogenesis and both follicle activity and tissue heterogeneity. Furthermore, the Thyroid

Auto-Regulation of the Thyroid Gland Beyond Classical Pathways

“…4). This latter hypothesis [25,34] finds support by recent observations made in patients with diverse thyroid dysfunctions, where cilia extensions are dependent on TSH-stimulation and/or TSH receptor signaling [57]. Therefore, our model entails that local auto-regulation via Taar1 at cilia of the apical pole of thyrocytes may be integrated with TSHstimulated thyroidal activities via basolateral TSH receptors.…”

Integrated miRNA and mRNA expression profiling identifies novel targets and pathological mechanisms in autoimmune thyroid diseases

“…However, in the contrary with these authors, we did not find any differences in cilia frequency in nodular hyperplasia, as has been previously reported by others [19]. Although these variable findings could be attributed to thyroid tissue heterogeneity [16], they could also be related to some degree of inflammation and/or autoimmunity that could have been overlooked in the pathological diagnosis.…”

“…Their findings circumscribe ciliary defects to Hürthle cells found in HT, although we observed a generalized effect throughout the tissue. Our findings in GD however, are consistent with a recent report in the literature which also described decreased ciliary frequencies and cilia length in GD [16]. However, in the contrary with these authors, we did not find any differences in cilia frequency in nodular hyperplasia, as has been previously reported by others [19].…”

“…Although the role of primary cilia in thyroid tissue remains obscure, some authors have suggested that they could be involved in thyroglobulin secretion and/or control mechanosensory events [13], [14], [15]. Recently, defective ciliogenesis have been associated with thyoid pathology, however no molecular mechanisms were identified [16].…”

Trace Amine-Associated Receptor 1 Trafficking to Cilia of Thyroid Epithelial Cells

“…Cilia of thyroid epithelial cells are involved in the regulation and maintenance of thyroid homeostasis and intact follicle structure [ 1 , 2 , 3 , 4 , 5 , 6 ]. Thyrocytes in well-polarized states expose one primary immotile cilium per cell that is identified by the cilia marker acetylated alpha-tubulin [ 1 , 2 , 4 ]. The primary cilium extends from the apical surface of polarized thyroid epithelial cells, e.g., in confluent cultures of Fisher rat thyroid (FRT) cells.…”