Laryngeal endocrine cells: topographic distribution and adaptation to chronic hypercapnic hypoxia

Abstract

The morphology, topographic distribution, effects of denervation, and exposure to hypercapnic hypoxia of endocrine cells were examined in rat larynx. The endocrine cells, which were immunoreactive for protein gene product 9.5 (PGP 9.5) and calcitonin gene-related peptide (CGRP), were observed within the epithelial layer of the laryngeal cavity and in the laryngeal gland, while solitary endocrine cells with apical and/or basal cytoplasmic processes appeared near the glottis. After denervation of the left cervical vagosympathetic trunk and the superior laryngeal nerve, the number of mucosal endocrine cells in the denervated side was not significantly different from that in the intact side. After exposure to hypercapnic hypoxia for 3 months, the number of endocrine cells with PGP 9.5 and CGRP was markedly increased. In conclusion, the secretion of laryngeal endocrine cells may be stimulated by CO 2 rather than O 2 . Furthermore, the endocrine cells and the sensory and autonomic nervous system may regulate each other by an axon reflex mechanism. Endocrine cells appear to play a very important role in the local regulation of the laryngeal mucosa.

A Study of Moderately Differentiated Neuroendocrine Carcinomas of the Larynx and an Examination of Non‐Neoplastic Larynx Tissue for Neuroendocrine Cells

“…The neuroendocrine cells, most frequent in the subglottic region, were immunoreactive with calcitonin gene‐related peptide (CGRP), substance P (SP), 5‐hydroxytryptamine, protein gene product 9.5 (PGP 9.5), and neuron‐specific enolase and contained electron‐dense cored vesicles. Yamamoto et al 25 showed in the rat laryngeal epithelium the presence of similar neuroendocrine cells, which were mainly distributed near the glottic area. In both species, the cells were in close vicinity of subepithelial nerve fibers, suggesting an afferent or efferent regulatory function.…”

Well-differentiated Neuroendocrine Carcinoma of the Larynx: Confusion of Terminology and Uncertainty of Early Studies

“…Experimentally, these cells do have an innate proliferative activity, as it is suggested by their increased numbers in rodents following antigenic or oxygenation challenging. 11,12 However, as mentioned above, laryngeal WD-NECs are commonly supraglottic, and non-neoplastic laryngeal neuroendocrine cells are more abundant in the subglottis. 13 Another theory of origin suggests that an altered microenvironment could cause the acquisition of "neuroendocrine" phenotypes by "'reserve" progenitor, basal cells of laryngeal epithelia.…”

Terminology and classification of neuroendocrine neoplasms of the larynx

“…The diffuse neuroendocrine system is composed of a wide variety of cells from the central nervous system, peripheral nervous system, and virtually all organs, all of which have the common phenotype of producing biologically active amines or peptides such as calcitonin, chromogranin‐A, bombesin, serotonin, and cholecystokinin. 2 Neuroendocrine cells can be found in the laryngeal mucosa of animals and humans by various techniques 3–11 and appear to have diverse functions ranging from oxygen sensing to regulation of local epithelial cell growth and regeneration to affecting nearby vasculature and/or autonomic nerve terminals. The term “neuroendocrine neoplasm” has been accepted to encompass a variety of different tumors arising in the larynx and having these features.…”