In fact, hyaluronic acid has been described as the extracellular matrix molecule that not only contributes to the maintenance of an optimal tissue viscosity that allows phonation, but also of an optimal tissue stiffness that allows frequency control. CD44 is a cell surface receptor for HA. Cells such as fibroblasts are responsible for synthesizing extracellular matrix molecules. Cell surface matrix receptors in return, feed back to the cells through cell-matrix interaction, allowing the cell to regulate its metabolism. Sato et al. carried out a histopathologic investigation of unphonated human vocal cords. Vocal fold mucosae, which were unphonated since birth, of three young adults (17, 24, and 28 years old) were looked at using light and electron microscopy. The results show that the vocal fold mucosae were hypoplastic, and rudimentary, and like newborns, did not have any vocal ligament, Reinke's space, or layered structure. Like newborns, the lamina propria appeared as a uniform structure. Some stellate cells were present in the macula flava, but started to show some signs of degeneration. The stellate cells synthesized fewer extracellular matrix molecules, and the cytoplasmic processes were shown to be short and shrinking, suggesting a decreased activity. Those results confirm the hypothesis that phonation stimulates stellate cells into producing more extracellular matrix. Furthermore, using a specially designed bioreactor, Titze et al. showed that fibroblasts exposed to mechanical stimulation have differing levels of extracellular matrix production from fibroblasts that are not exposed to mechanical stimulation. The gene expression levels of extracellular matrix constituents such as fibronectin, MMP1, decorin, fibromodulin, hyaluronic acid synthase 2, and CD44 were altered. All those genes are involved in extracellular matrix remodeling, thus suggesting that mechanical forces applied to the tissue, alter the expression levels of extracellular matrix related genes, which in turn allow the cells present in the tissue to regulate the extracellular matrix constituent synthesis, thus affecting the tissue's composition, structure, and biomechanical properties. In the end, cell-surface receptors close the loop by giving feedback on the surrounding extracellular matrix to the cells, affecting also their gene expression level. Impact of hormones Other studies suggest that hormones play also an important role in vocal fold maturation. Hormones are molecules secreted into the blood stream to be delivered at different targeted sites. They usually promote growth, differentiation and functionality in different organs or tissues. Their effect is due to their ability to bind to intracellular receptors, modulating the gene expression,