Functional estrogen receptors alpha and beta are expressed in normal human salivary gland epithelium and apparently mediate immunomodulatory effects

Abstract

Salivary gland epithelial cells (SGECs) have been shown to participate in immunological responses and have been implicated in the pathogenesis of Sjögren's syndrome (SS). Experimental evidence from animal models indicates that estrogen deficiency may also participate in SS pathogenesis. However, the expression and functionality of the estrogen receptors alpha (ERalpha) and beta (ERbeta) in normal human salivary epithelium is unknown. To investigate these points, formalin-fixed, paraffin-embedded specimens and cultured non-neoplastic SGEC lines derived from nine minor salivary gland (MSG) biopsies with normal histology were studied. Immunohistochemical analyses detected the epithelial expression of ERalpha, ERbeta1, and ERbeta2 protein isoforms both in MSG tissues and in cultured SGECs. Such epithelial expression was verified by immunoblotting of various ER proteins in cellular extracts of cultured SGECs (full-length-ERalpha, ERalpha-Delta3, ERbeta1-long, ERbeta1-short, and ERbeta2-long isoforms). Estrogens did not induce growth or apoptosis in cultured SGECs. However, similarly to other cellular systems, treatment of cultured SGECs with estrogens (17beta-estradiol and the ERalpha- and ERbeta-selective agonists propylpyrazole-triol and diarylpropiolnitrile, respectively) inhibited the interferon-gamma-inducible expression of intercellular adhesion molecule-1. This finding corroborated the functionality of ER expressed by SGEC. Our results suggest that salivary epithelium expresses constitutively functional ERalpha and ERbeta proteins that apparently mediate immunomodulatory effects.

Salivary Profile and Xerostomia on the Elderly in Depok, West Java, Indonesia: Analysis of Demographic Factors and Systemic Disease

“…Estrogen has a role in regulating epithelial maturation; thus, the decreased level of estrogen hormone such as found in post-menopausal women contributes to reduced epithelial cell maturation, leading to a thinning epithelium and atrophy. Thus, it is common to find postmenopausal women who suffer from discomfort in oral mucosa and reduced saliva secretion [4].…”

Effect of Biochanin A versus 17β estradiol in rat submandibular salivary gland

“…Nevertheless, Tsinti et al (18) reported the absence of an impact of estrogen on cell apoptosis in vitro via salivary gland cell culture. These differences in observation may be attributed to the more complicated in vivo environment when compared with the in vitro environment (29,45,46).…”

“…SMG removal (sialoadenectomy) increased estrogen production and uterine weight; on the other hand, ovarian estrogen could be inhibited by the submandibular gland via inhibition of ovarian androgen production (17). Additionally, the expression of estrogen receptors (predominantly ERβ) is higher in the submandibular gland when compared with the other major salivary glands, thus implicating the role of salivary glands in the development and/or regeneration of reproductive organs and peripheral organs (16)(17)(18).…”

Effects of ovariectomy, estrogen and soy isoflavones in rats submandibular glands

“…Salivary glands are not classic target organs of female sex hormones, but the influence of these hormones on these glands has been studied [4][5][6][7]; however, knowledge concerning this interaction remains scarce.…”