Abstract
Purpose :
Sex and sex hormones are known to affect the functions of meibomian glands (MGs). Androgens have been shown to promote MG function, but the role of estrogens in MGs is less well defined. In this study, the expression of sex hormone receptors in human MGs was examined, and the effect of loss of estrogen and estrogen receptors (ERs) on MGs was investigated using the gene knockout (KO) mouse models.
Methods :
Human tarsal plate tissues were retrieved from the cadaveric donors to examine the expression patterns of sex hormone receptors in the MGs by immunofluorescence. Knockout (KO) mice with respective deletion of aromatase (Aro, an estrogen synthase) or estrogen receptor (ER) isoforms, ERα and ERβ, were used to examine the changes in the MGs when compared to the age- and sex-matched wild type (WT) control mice.
Results :
In human MGs of both sexes, androgen receptor (AR), ERα and ERβ, were found in the nuclei of meibocytes, suggesting that the canonical nuclear receptor pathways are activated in these cells. When compared with the WT mice aged from 3 to 12 months, no evident morphological differences were noticed in the MGs of male or female Aro, ERα and ERβ, knockout (KO) mice. In the MGs of female WT mice, the AR immunofluorescence was mostly located in the cytoplasm of the acinar basal cells. However, the nuclear localization of AR was markedly enhanced in the early stage meibocytes of the female Aro- and ERα- (but not ERβ-) KO mice. In the male Aro- and ERα KO mice, the proportion of AR-positive nuclei was also increased in the newly differentiated meibocytes when compared to the age-matched male WT mice, but to a much less extent than that in the female KO mice. These results together suggest that the estrogen and ERα activity counteract the AR-nuclear signal, particularly in the MGs of the female mice.
Conclusions :
The nuclear localization of AR and ER isoforms in the meibocytes of human MGs substantiates the critical role of sex steroid receptors as the ligand-activated transcription factors for gene expression in the MGs. The findings from KO mice revealed for the first time that estrogen and ERα can counteract the AR-nuclear signal in MGs as a “yin-yang” relationship of hormonal balance during meibocyte differentiation. Our data further supports the current consensus that lower androgen and higher estrogen enhance the susceptibility of developing MGD and DED.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.