Differential Responses to Steroid Hormones in Fibroblasts From the Vocal Fold, Trachea, and Esophagus

Abstract

There is accumulating evidence that fibroblasts are target cells for steroids such as sex hormones and corticoids. The characteristics of fibroblasts vary among tissues and organs. Our aim in this study is to examine differences in responses to steroid hormones among fibroblasts from different cervicothoracic regions. We compared the actions of steroid hormones on cultured fibroblasts from the vocal folds, which are considered to be the primary target of steroid hormones, and the trachea and esophagus in adult male rats. Expression of steroid hormone receptors (androgen receptor, estrogen receptor α, and glucocorticoid receptor) was identified by immunofluorescence histochemistry. Androgen receptor was much more frequently expressed in fibroblasts from the vocal fold than in those from the trachea and esophagus. Cell proliferation analysis showed that administration of testosterone, estradiol, or corticosterone suppressed growth of all 3 types of fibroblasts. However, mRNA expression for extracellular matrix-associated genes, including procollagen I and III and elastin, and hyaluronic acid synthase I was elevated only by addition of testosterone to fibroblasts from the vocal fold. These results indicate that each steroid hormone exerts region-specific effects on cervicothoracic fibroblasts with different properties through binding to specific receptors.

Phosphorylation of the glucocorticoid receptor alters SMAD signaling in vocal fold fibroblasts

“…The distribution of total GR in HVOX indicated that ligand binding led to near complete nuclear localization of the receptor, which is consistent with our previous reports . DM acted on human VFFs directly via GR.…”

“…The distribution of total GR in HVOX indicated that ligand binding led to near complete nuclear localization of the receptor, which is consistent with our previous reports. 12,17 DM acted on human VFFs directly via GR. Similarly, the distribution of Ser203 and Ser211 phosporylation was also consistent with our previous report, 17 suggesting that differentially phosphorylated receptor residues were located in unique subcellular compartments, likely modulating distinct aspects of receptor function.…”

Effect of sex hormones on extracellular matrix of lamina propria in rat vocal fold

“…These results are similar to those of Mikudai et al, who found no marked differences of the ECM proteins in rat vocal fold after castration. 16 These results suggest that testosterone has no effect on the Fig. 3.…”

“…Although the change of testosterone is one of the factors that influence vocal fold activity and voice production, there were not significantly changes in the thickness and production and degradation of ECM of vocal fold lamina propria in ORX rats. These results are similar to those of Mikudai et al , who found no marked differences of the ECM proteins in rat vocal fold after castration . These results suggest that testosterone has no effect on the production and degradation of ECM proteins in the vocal fold lamina propria.…”

Loss of Estrogen Receptors is Associated with Increased Tumor Aggression in Laryngeal Squamous Cell Carcinoma

“…Estrogen exerts regionally specific effects on cell proliferation and mRNA expression of extracellular matrix (ECM)-associated genes in normal fibroblasts. Cervicothoracic fibroblasts from the vocal fold, trachea, and esophagus have been shown to respond differently to estrogen based on their specific estrogen profiles 20 . Studies examining the presence of ERα in vocal cord fibroblasts show that it is localized predominantly in the nucleus and cytoplasm 7 .…”