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

Abstract

Objectives The role of sex hormones for voice changes in men and women is presently unknown. To determine the effect of sex hormone on the vocal fold, changes of the extracellular matrix (ECM) in vocal fold lamina propria were assessed in orchiectomized (ORX) and ovariectomized (OVX) rats. Methods Male and female Sprague‐Dawley rats were divided into sham‐operated control male (CON‐ORX), ORX, sham‐operated female (CON‐OVX), and OVX rats. Histological changes and expression of ECM‐related genes in lamina propria of the vocal fold were evaluated at 4 and 12 weeks after surgery. Results Testosterone and estradiol levels decreased in the ORX and OVX groups, respectively. ORX groups did not have significant changes compared with CON‐ORX groups. However, the expression of hyaluronic acid (HA) was decreased in the OVX group compared with the CON‐OVX group. The expression of collagen I in OVX was lower than in the CON‐OVX group. Collagen III levels were elevated at 4 weeks in the OVX group, but collagen III levels were diminished at 12 weeks in the OVX group. Expression of elastin in the ECM was less dense in the OVX group compared with controls. The expression MMP‐1 and MMP‐9 showed significantly increase in the OVX group compared to the CON‐OVX group. Conclusion No changes of the ECM‐related genes in the vocal fold lamina propria were observed in ORX groups with reduced testosterone. However, changes of several ECM‐related genes were observed in OVX groups with decreased estrogen. These results indicate that the vocal fold is an estrogen‐sensitive target organ and that decreased estrogen, not testosterone, can affect the expression of several ECM‐related molecules of vocal fold. Level of Evidence NA Laryngoscope, 130:732–740, 2020

The Protective Effect of Echinochrome A on Extracellular Matrix of Vocal Folds in Ovariectomized Rats

“…Drugs 2020, 18, 77 9 of 15 expression levels of Has 2, 3 and Eln were slightly different, but the changes in hyaluronic acid and elastin in vocal fold lamina propria were insignificant. These findings differed in part from our previous findings at 12 weeks after ovariectomy [6]. The change in ECM owing to the reduction in estradiol seems to be somewhat different over time.…”

“…In contrast, hyaluronic acid concentration and elastin levels were not significantly different in all groups and ECH treatment had no influence on the expression level of hyaluronic acid and elastin until 6 weeks after ovariectomy. According to our previous study, hyaluronic acid concentration and elastin levels significantly decreased at 12 weeks after ovariectomy [6]. Thus, collagen synthesis and degradation seem to be the most important factors controlling early voice change caused by menopause.…”

“…Our previous study evaluated voice changes induced by sex hormones [17]. We have previously reported the effects of ECM production and degradation on vocal fold lamina propria in ovariectomized rats [6]. Population surveys show that many women report voice deepening after menopause, but this observation was not common among men of similar age [18].…”

“…ERβ expression was similar between all groups ( Figure 2B). According to our previous research, Esr1 expression was undetected on the lamina propria of female vocal fold with qPCR [6]. Hence, we evaluated the expression levels of Esr2a and Esr2b using qPCR.…”

“…During menopause, the decrease in the amount of estrogen causes dysfunctions of the connective tissues via ECM degradation. Previous studies have shown that the vocal fold is an estradiol-sensitive target organ and any decrease in estradiol levels may affect the expression of several ECM-related molecules in the vocal fold [6]. Hormone therapy is commonly used for the treatment of several menopausal symptoms and for the alleviation of menopausal voice complaints, but adverse-effects of hormone therapy have been reported [7][8][9].…”