Recent insights into the cell biology of thyroid angiofollicular units.

Abstract

In thyrocytes, cell polarity is of crucial importance for proper thyroid function. Many intrinsic mechanisms of self-regulation control how the key players involved in thyroid hormone (TH) biosynthesis interact in apical microvilli, so that hazardous biochemical processes may occur without detriment to the cell. In some pathological conditions, this enzymatic complex is disrupted, with some components abnormally activated into the cytoplasm, which can lead to further morphological and functional breakdown. When iodine intake is altered, autoregulatory mechanisms outside the thyrocytes are activated. They involve adjacent capillaries that, together with thyrocytes, form the angiofollicular units (AFUs) that can be considered as the functional and morphological units of the thyroid. In response to iodine shortage, a rapid expansion of the microvasculature occurs, which, in addition to nutrients and oxygen, optimizes iodide supply. These changes are triggered by angiogenic signals released from thyrocytes via a reactive oxygen species/hypoxia-inducible factor/vascular endothelial growth factor pathway. When intra- and extrathyrocyte autoregulation fails, other forms of adaptation arise, such as euthyroid goiters. From onset, goiters are morphologically and functionally heterogeneous due to the polyclonal nature of the cells, with nodules distributed around areas of quiescent AFUs containing globules of compact thyroglobulin (Tg) and surrounded by a hypotrophic microvasculature. Upon TSH stimulation, quiescent AFUs are activated with Tg globules undergoing fragmentation into soluble Tg, proteins involved in TH biosynthesis being expressed and the local microvascular network extending. Over time and depending on physiological needs, AFUs may undergo repetitive phases of high, moderate, or low cell and tissue activity, which may ultimately culminate in multinodular goiters.

• Authors: Ides M Colin, Jean-François Denef, Benoit Lengelé, Marie-Christine Many, Anne-Catherine Gérard
• Journal: Endocrine reviews (Endocr Rev) Vol. 34 Issue 2 Pg. 209-38 (Apr 2013) ISSN: 1945-7189 [Electronic] United States
• PMID: 23349248 (Publication Type: Journal Article, Review)

Chemical References

• Thyroid Hormones
• Iodine

Topics

• Goiter, Nodular (etiology, metabolism)
• Humans
• Iodine (metabolism)
• Neovascularization, Physiologic (physiology)
• Thyroid Gland (blood supply, cytology, metabolism, physiology)
• Thyroid Hormones (biosynthesis, metabolism)