**2.2. C cells as a member of the Diffuse Neuroendocrine System**

52 Thyroid Hormone

epithelium [3].

the UBB, where they secrete calcitonin [8].

hypophosphatemic hormone (Figure 1).

The thyroid follicles are composed of two different endocrine cell populations: (1) the **follicular cells**, the most abundant endocrine cells in the gland and responsible for secreting T3 and T4, hormones that control the basal metabolism; (2) **C cells** or **parafollicular cells**, which are very scarce and mainly known for producing calcitonin (CT), a hypocalcemic and

**Figure 1.** Schematic diagram of the histological components of the normal thyroid gland.

**2.1. Embryological development of the thyroid gland and origin of C cells** 

The thyroid gland has a dual embryonic origin. Most of the thyroid gland derives from the medial anlage, a ventral outpocketing of the foregut endoderm at the level of the first pair of pharyngeal pouches. The medial anlage appears as a bilobulate vesicular structure at the foramen caecum of the tongue. It then descends as a component of the thyroglosal duct to reach its definitive position in the neck. After involution of the thyroglosal duct, the thyroid anlage begins to expand laterally to form two lateral lobes and a medial isthmus between them. Consequently, the medial anlage gives rise to most, if not all, of the follicular

On the other hand, C cells derive from the ultimobranchial bodies (UBB), two outpocketings of the forth-fifth pharyngeal pouch complexes that lose their connection and migrate centrally to fuse with the medial thyroid anlage. Fusion typically occurs slightly above to the middle of the lateral lobes. After incorporation into the larger medial anlage, cells of the UBB disperse into the surrounding thyroid tissue and give rise to C cells. UBB may also contribute to the formation of a minimal part of thyroid follicular cells [4]. Finally, portions of the UBB persist in the postnatal thyroid glands as small cystic structures -the "**ultimobranchial follicles**"- in rodents [5], or as "**solid cell nests**" in humans [6]. Estimates of the relative contributions to thyroid weight from the lateral anlage range from less than 1 to 30% in humans [7]. In non-mammal vertebrates, the embryonic thyroid and UBB develop as separate structures, thus, C cells are confined to the ultimobranchial glands derived from Classically, C cells formed part of the APUD system (term created by Pearse in 1966 [11] from the initial letters of *Amine Precursor Uptake and Decarboxylation*), a collection of cells of neuroectodermal origin, characterized by having as their primary function the production of endocrine peptides which are stored in secretory granules, and the common possession of a number of cytochemical and ultrastructural properties, in whatever situation they occur. Subsequently, further evidence indicated that only very few of the original series of APUD cells were definitively derived from the neural crests.

Nevertheless, according to Pearse [12], whenever APUD cells occur they could properly be regarded as "neuroendocrine cells" for synthesizing peptides (neuropeptides) common to both the nervous and endocrine systems. Additionally, as not all of these cells accumulate amine precursors, the designation APUD was finally replaced by Pearse in 1977 [12] with a new concept, the *Diffuse Neuroendocrine System* (DNES). The DNES includes, besides C cells, gastroenteroendocrine cells, pancreatic islet cells, bronchopulmonary and urogenital endocrine cells, adenohypophyseal cells, parathyroid cells and chromaffin cells of the adrenal medulla, carotid body, and sympathetic ganglia [13].
