Effects of estrogen on STIM1/Orai1 in the sublingual gland of ovariectomized rats.

Background. Studies have shown that estrogen can protect the function of the sublingual gland, but the specific mechanism is still unclear. Besides, the STIM1/Orai1 pathway is important to secretion in the salivary gland. Here, we explore the possible effects of estrogen on sublingual gland function by observing changes of STIM1 and Orai1 levels in the sublingual glands of ovariectomized rats. Methods. 42 adult female Sprague-Dawley rats were randomly divided into three groups: SHAM, OVX, and OVX+E (n=14 per group). Two weeks after ovariectomy, rats were treated with estrogen (beta-estradiol). The expression of STIM1 and Orai1 in the sublingual gland were observed by double label-immunohistochemistry and immunofluorescence. Calcium imaging was conducted to observe changes in cellular Ca2+ levels. Results. IHC and IF showed that the levels of both STIM1 and Orai1 decreased following ovariectomy, but increased to SHAM levels after estrogen treatment. By IF, STIM1 and Orai1 exhibited perfect co-localization. Calcium imaging results showed that the Ca2+ in the cells decreased after ovariectomy. Estrogen intervention returned levels of these proteins and Ca2+ to the same as those in the control group. Conclusion. This study demonstrates that low estrogen status significantly reduced the expression of STIM1 and Orai1 in the sublingual gland of rats, along with cellular Ca2+ levels. These data provide insight into the likely mechanisms underlying sublingual gland secretion dysfunction during menopause.