Increased Expression of Estrogen Receptor Beta in Idiopathic Progressive Subglottic Stenosis

Abstract

Background/ObjectivesIdiopathic progressive subglottic stenosis (IPSS) predominantly affects females in perimenopause. It has, therefore, been hypothesized that estrogen is involved in its pathogenesis. There are two main types of estrogen receptors: ER‐α and ER‐β. Abnormal variants of ER‐β have previously been shown to be associated with poor wound healing. Estrogen receptors have recently been identified in subglottic tissue samples, with elevated levels of ER‐α and progesterone receptors, and no expression of ER‐β, in stenotic specimens reported in one study. The objective of this study was to confirm the presence of estrogen receptors in the subglottis and investigate levels of expression and types of estrogen receptors in normal and stenotic subglottic tissue.MethodsSubglottic tissue was obtained from three female and one male cadaver without laryngotracheal pathology to serve as controls. Subglottic tissue specimens from five female patients with IPSS were also analysed. Immunofluorescence stains for ER‐α and ER‐β were performed on specimens. Staining patterns were compared qualitatively and semi‐qualitatively between control and IPSS specimens.ResultsImmunofluorescence stains demonstrated the presence of both ER‐α and ER‐β in subglottic tissue. IPSS specimens demonstrated significantly greater staining intensity of ER‐α in the epithelium and ER‐β in glands and ducts compared to controls.ConclusionsThis study confirms the presence of estrogen receptors in the subglottis. Increased expression of ER‐α in the epithelium and ER‐β in glands and ducts in IPSS compared to controls may help to explain the predisposition to stenosis in these individuals.Level of Evidence3b Laryngoscope, 130:2186–2191, 2020

Idiopathic Subglottic Stenosis during Pregnancy: A Support Group Survey

“…No definitive cause of iSGS has been identified, but because the initial presentation often coincides with menopause, the underlying belief is that the disease process is hormonally mediated. [16][17][18] Some evidence suggests that subglottic narrowing and deposition of collagen is mediated by estrogen. 19,20 Certainly, hormonal changes occur during pregnancy as well, thus, presentation during pregnancy would not be unexpected.…”

Laryngotracheal stenosis: Mechanistic review

“…The following year, Damrose et al demonstrated the presence of ER‐α and ER‐ß in subglottic tissues using immunofluorescence. Relative to control tissues, iSGS specimens demonstrated a significantly greater intensity of ER‐α in the epithelium, and ER‐ß in the submucosal glands and ducts 45 …”

“…Relative to control tissues, iSGS specimens demonstrated a significantly greater intensity of ER-α in the epithelium, and ER-ß in the submucosal glands and ducts. 45 These recent studies provide some early support for estrogen activity in the subglottis, with differential receptor expression in iSGS patients when compared to normal controls. Given the well-described impact of estrogen on dermal wound healing, further study is warranted to better define the role of estrogen in the etiology and pathophysiology of iSGS.…”

Prevalence and incidence of idiopathic subglottic stenosis in southern and central Alberta: A retrospective cohort study

“…Although iSGS is a diagnosis of exclusion, it interestingly affects a homogenous population of primarily perimenopausal, Caucasian females [ 2 , 8 – 10 ]. The specific etiology of iSGS remains unclear, however proposed pathophysiological factors include gastroesophageal reflux disease (GERD), upregulation of estrogen receptors in the subglottis, pathogenic bacterial flora, and epigenetic changes to inflammatory constituents of the subglottic mucosa [ 11 – 14 ].…”