Influence of age and gender on sex steroid receptors in rat masticatory muscles

Abstract

The temporomandibular muscle dysfunction is characterized by myofascial pain and is more prevalent in women of reproductive age. Sex steroid hormones are hypothetically involved in the dysfunction, but few are the studies of steroid receptors in masticatory and mastication-related muscles. Our aim was to determine estrogen and testosterone receptor expression in rat masticatory and mastication-related muscles within the context of age and gender. Twelve rats were equally divided into four groups: (a) 10-month-old females; (b) 10-month-old males; (c) 24-month-old females; and (d) 24-month-old males. Euthanasia of the females was performed in the proestrous phase (vaginal smears) and the masticatory and accessory muscles were removed for immunohistochemical analysis. Statistical analysis was performed with ANOVA and the Tukey test. Estrogen receptor expression was similarly low in all muscles and groups. Testosterone receptor expression in the Masseter muscle of the 24-month-old male rats was higher than that in the other groups and significantly superior to its expression in the Posterior Digastric muscle. In short, testosterone receptor expression was highest in old male rats. If we generalize to humans, this fact could indicate age- and sex-related hormonal influence on temporomandibular muscle dysfunction. Further studies, however, are necessary to strengthen this hypothesis.

Does temporomandibular disorder correlate with menopausal symptoms?

“…Inanimal models, there is evidence that hormones may affect TMJ-related muscles, similar to the case with senile female rats that show a drop in estrogen level 24 . Similarly, in menopausal women, hormonal changes are characteristic of this stage (menopausal transition and postmenopause) and may affect the intensity of TMD-induced pain.…”

“…Estrogen action in TMD is known to be carried out by structural mechanisms through the regulation of collagen synthesis in the condylar fibrocartilage and tropism of masticatory muscles, 14,17,24 as well as by nonstructural mechanisms via the TMJ nociceptive pathway, given that the expression of Nav 1.7 in the trigeminal ganglion increases in consonance with the serum estrogen level 19 . Theoretically, such mechanisms could reduce the threshold of TMD-induced pain 20 .…”

“…Inanimal models, there is evidence that hormones may affect TMJ-related muscles, similar to the case with senile female rats that show a drop in estrogen level. 24 Similarly, in menopausal women, hormonal changes are characteristic of this stage (menopausal transition and postmenopause) and may affect the intensity of TMD-induced pain. There is some inconclusive evidence pointing to the interference of hypoestrogenism in TMD-induced pain and the influence of menopausal symptoms on the disorder.…”

Pelvic floor muscle training program for women in the puerperal period: clinical progress after intervention

“…During pregnancy, the relative hypo-estrogenism, similar to climacterics, influences these patients' sexual intercourse and sexual dysfunction. Additionally, the muscles have estrogen and testosterone receptors that decrease with aging and reduction of ovarian function [23][24][25] . Besides that, the progressive increase in uterine volume increases intra-abdominal pressure and overload in the PF.…”

Sex as a Biological Variable in Oral Diseases: Evidence and Future Prospects

“…-Elevated nociceptive threshold in the presence of increased circulating levels of sex steroids (like pseudopregnancy) or in hormone treatment following ovariectomy -Estrogen and progesterone have an antagonistic effect on pain threshold Kayser et al (1996) Hindpaw and tail pressure stimulation in male vs. female rats for 3 wk -Females had higher thresholds for tail pressure than males -Female thresholds varied according to the period of menstrual cycle -Male rats did not display systematically variability in thresholds TMD is higher in female models TMJ formalin test in TMJ of female and male rats -0.5% formalin injected in TMJ induced nociceptive response in female rats and gonadectomized male rats but not in naive male rats -Testosterone at physiological level does not modulate acute TMJ pain, whereas it attenuates nociception in male rats at supraphysiological levels. This does not occur in female rats -The presence of testosterone receptors in masticatory muscles of male rodents plays a protective role and inhibits trigeminal nociception, reduces potential fatigue, and reduces development of TMJ pain Males and females have significant difference in proportion of fiber types in masseter and temporalis English et al (1999) Immunoblot and immunohistochemical analysis of masseter fibers of female and male rabbits -Males had more IIa MHC fiber and fewer I MHC fibers than females -Males contained larger IIa MHC than females Eason et al (2000) Immunoblot and immunohistochemical characterization of masseters of female and male rodents -Females presented with twice as many fibers IIa MHC fibers -Males contained twice as many IIb MHC fibers -Castration resulted in greater expression of IIa MHC fibers in males -Ovariectomy did not influence proportion of fiber type composition in females -Testosterone influenced the MHC expression fiber type in males Reader et al (2001) Immunoblot and immunohistochemical analysis of MHC of masseters in castrated rabbits infused with testosterone -Brief exposure to testosterone induces an MHC isoform switch -Exposure to testosterone significantly decreased the proportion of cardiac alpha MHC and increased proportion of IIa MHC (this latter declined within 6 wk) Widmer et al (2002) Immunoblot and immunohistochemical analysis of MHC of masseters in mice -Type IIa MHC of female masseters presented with 2 different sizes; male masseters only showed uniform dimension English and Widmer (2003) Intramuscular stimulation of masseters in female and male rabbits -Males had preponderance of type IIa MHC -Sex dimorphism in proportion of fiber phenotype is reflected in sex difference in motor unit and function -Males had greater magnitude and velocity of twitch forces and torques compared to females Galhardo et al (2019) Immunohistochemical analysis of masticatory muscles of rats of different sex and age groups -Proportion of testosterone receptors was significantly higher in masseter muscle of old male rats compared to young and female rats -No statistically significant difference was seen in the other groups mice (Valerio et al 2017). When exposed to bacterial LPS, neutrophils from male mice exhibited significantly higher mRNA expression of Il-1b, Il-6, Il-10, Tnf-α, Cxcl1, Cxcl2, Cxcl3, Cxcl10, and inducible nitric oxide synthase in comparison to females.…”