**2. Histological organization of the thyroid gland**

The thyroid gland consists of two lobes connected by a narrow band of thyroid tissue called the isthmus, located in the midportion of the neck, immediately in front of the larynx and trachea. Each lobe of the thyroid gland consists of numerous follicles, the **thyroid follicles,**  which constitute the structural and functional unit of the gland. Each follicle consists of a simple layer of cuboidal epithelial cells, the **follicular epithelium,** enclosing a central lumen containing a **colloid** substance rich in **thyroglobulin,** an iodinated glycoprotein, yielding a periodic-Schiff (PAS)-positive reaction. The shape of the normal follicles varies from round to oval and they show a considerable size variation depending on the degree of gland activity (Figure 1).

© 2012 Martín-Lacave et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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 hypophosphatemic hormone (Figure 1).

Paracrine Regulation of Thyroid-Hormone Synthesis by C Cells 53

Since Le Douarin and Le Lievre study [9] confirmed, using chick-quail chimeras, that avian ultimobranchial C cells originate from the neural crests, it was assumed, without much supporting evidence, that mammalian thyroid C cells also originate from the neural crest via the UBB. Nevertheless, the neuroectodermical origin of C cells in mammals is currently a controversial subject. In fact, Kameda et al. [10] have recently presented evidence that murine C cells are derived from the endodermal epithelial cells of the last pharyngeal pouch

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

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

C cells represent the neuroendocrine cells that produce calcitonin in the thyroid gland. Since their discovering by Baber in 1876, these cells have been given many different terms. However, the two most common denominations employed are *C cells* and *parafollicular cells*. The name "C cell" was coined by Pearse in 1966 and it is reflective of calcitonin production; this term is preferred to that of "parafollicular cell" as these cells are not always related to follicles in parafollicular position and may, furthermore, be found outside the thyroid gland, unrelated to follicles, as occurs in the ultimobranchial glands in non-mammal vertebrates [11]. C cells are difficult to identify in formalin-fixed, paraffin-embedded sections stained with H&E. Generally, their nuclei are somewhat larger and paler than those of follicular cells. Therefore, the most reliable procedure for the identification of C cells involves the use of

C cells have variable shapes ranging from polygonal to spindled. The location of C cells relative to follicular cells also varies. They may be found between follicular cells or completely peripheral to the follicular epithelium. C cells are typically separated from the

immunohistochemical procedures with antibodies for calcitonin (Figure 2).


cells were definitively derived from the neural crests.

adrenal medulla, carotid body, and sympathetic ganglia [13].

**2.3. Normal morphology and distribution of C cells** 

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