Figure 3 - uploaded by Hae-Hyeog Lee
Content may be subject to copyright.
The expression of 1,25-dihydroxyvitamin D 3 receptor (VDR), estrogen receptor (ER)-β, and ezrin in the human vagina and vitamin D state. (A) Vitamin D insufficiency state (<10 ng/mL), (B) Vitamin D deficiency state (10-30 ng/mL). The menstrual phases were histologically confirmed as proliferative phase. (C) The intensity of each signal was quantified and is represented in the graph. Statistical analysis of vitamin D receptor (VDR) (Mann-Whitney U-test, p= 0.537), estrogen receptor (ER)-β (Student's t-test, p= 0.545), and ezrin expression (Mann-Whitney U-test, p= 1.000). NC= negative control. 

The expression of 1,25-dihydroxyvitamin D 3 receptor (VDR), estrogen receptor (ER)-β, and ezrin in the human vagina and vitamin D state. (A) Vitamin D insufficiency state (<10 ng/mL), (B) Vitamin D deficiency state (10-30 ng/mL). The menstrual phases were histologically confirmed as proliferative phase. (C) The intensity of each signal was quantified and is represented in the graph. Statistical analysis of vitamin D receptor (VDR) (Mann-Whitney U-test, p= 0.537), estrogen receptor (ER)-β (Student's t-test, p= 0.545), and ezrin expression (Mann-Whitney U-test, p= 1.000). NC= negative control. 

Source publication
Article
Full-text available
Vitamin D plays a critical role in the regulation of growth and differentiation of squamous epithelium. The pleiotropic effects of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], include proliferative, pro-apoptotic, and pro-differentiation effects on numerous cell types. Although 1,25-dihydroxyvitamin D3 is involved in the regulation and differentiation o...

Context in source publication

Context 1
... the insufficient group, VDR was slightly more expressed than in the deficient group, but ER-β and ezrin showed the opposite pattern. In addition, ER-β and ezrin expression were increased in vaginal tissues from the vitamin D deficient group (Figure 3), although these differences were not statistically significant [VDR (p=0.537), ER-β (p=0.545), ...

Citations

... Vitamin D receptor (VDR) are widely distributed in cells of various tissues in the body, and Vitamin D binding to VDR affects the expression of a number of genes. VDR are found in the basal cell layer of vaginal tissue [11] Vitamin D is involved in the growth and differentiation of vaginal epithelial cells and promotes maturation of the vaginal epithelium. Kamronrithisorn et al., found that weekly administration of 40,000 IU of Vitamin D to postmenopausal women resulted in a significant improvement in vaginal maturation indices and dryness symptoms [12]. ...
... Vitamin D exerts its biological role mainly by the binding of 1,25(OH) 2 D 3 to VDR. Immunohistochemistry demonstrates that VDR localises to the basal and suprabasal layers of vaginal epithelial cells [11]. Mouse progenitors represent epithelial cells in culture whose terminal differentiation is regulated by 1,25(OH) 2 D 3 [26]. ...
Article
Full-text available
Atrophic vaginitis is very common in postmenopausal women due to declining estrogen levels. Vitamin D plays an important role in promoting epithelial cell proliferation, migration and adhesion. We established a rat model of ovariectomy (OVX) induced atrophic vaginitis with the aim of investigating the effects of Vitamin D supplementation on the vaginal epithelial barrier. The results showed that ovariectomised rats had significantly higher vaginal pH, reduced Lactobacillus, significantly lower uterine and vaginal weights, and lower vaginal epithelial PCNA, occludin, and E-cadherin mRNA expression compared with sham-operated rats. Vitamin D supplementation could reduce the vaginal pH, promote the proliferation and keratinization of vaginal epithelial cells, enhance the expression of PCNA mRNA in vaginal tissues, and improve the vaginal and uterine atrophy. Vitamin D can also increase the expression of E-cadherin and occludin proteins in vaginal tissues, maintain the integrity of the vaginal epithelium, increase the number of Lactobacillus, and reduce pathogenic bacterial infections. In vitro experiments demonstrated that 1,25(OH)2D3 could promote the proliferation and migration of VK2/E6E7 vaginal epithelial cells and increase the expression of E-cadherin protein. In conclusion, we demonstrated that Vitamin D can regulate the expression of vaginal epithelial tight junction proteins, promotes cell proliferation, and improves vaginal atrophy due to estrogen deficiency.
... Long-term vitamin D supplementation has shown increased vaginal epithelial cell proliferation and VDR expression in rats [23,24] and post-menopausal women [25]. In premenopausal women, VDR expression in the vagina is also dependent on systemic vitamin D levels, as well as the phase of the menstrual cycle [26]. ...
... While VDR gene expression has previously been shown to correlate with plasma vitamin D status and antiviral factors in genital mucosa [5] in healthy participants, we saw no changes in CV mucosal VDR expression or correlation with antiviral activity (data not shown). Furthermore, although we did not see a significant change in VDR expression, the expression of VDR can be regulated by other factors outside of vitamin D. Menstrual phase has been shown to have some effect on VDR expression, and a quantifiable but non-significant negative link between serum 25(OH)D and vaginal VDR expression has been reported [26]. While we cannot rule out the potential impact of the menstrual cycle on VDR expression because we did not measure serum hormone levels during this study, preand post-supplementation visits were both scheduled during the luteal phase to lessen the impact of hormone levels, and therefore on changes in VDR, or other key factors expression. ...
Article
Full-text available
While vitamin D insufficiency is known to impact a multitude of health outcomes, including HIV-1, little is known about the role of vitamin D-mediated immune regulation in the female reproductive tract (FRT). We performed a pilot clinical study of 20 women with circulating 25(OH)D levels <62.5 nmol/L. Participants were randomized into either weekly or daily high-dose oral vitamin D supplementation groups. In addition to serum vitamin D levels, genital mucosal endpoints, including soluble mediators, immune cell populations, gene expression, and ex vivo HIV-1 infection, were assessed. While systemic vitamin D levels showed a significant increase following supplementation, these changes translated into modest effects on the cervicovaginal factors studied. Paradoxically, post-supplementation vitamin D levels were decreased in cervicovaginal fluids. Given the strong correlation between vitamin D status and HIV-1 infection and the widespread nature of vitamin D deficiency, further understanding of the role of vitamin D immunoregulation in the female reproductive tract is important.
... Vitamin D3 binds to an intracellular receptor that is a member of the steroid-thyroid hormone receptor family. Vitamin D3 and its receptors form a complex that binds to the Vitamin D3 response element of genes and either positively or negatively affects the transcription of that gene [18,19]. The importance of this review: Being free of sexual problems can improve the confidence and mental state of women [20]; therefore, it is important to resolve sexual problems associated with menopause. ...
Article
Full-text available
Menopause is associated with the onset of climacteric symptoms due to low estradiol levels, which may cause insufficient maturation of the vaginal mucosa. Vitamin D may regulate the growth and differentiation of cells that are adversely affected due to low estradiol levels, thereby restoring vaginal health. The objective of this systematic review, the first on this subject, was to investigate the effect of vitamin D on the vaginal health of menopausal women. PubMed, Embase, Scopus, Web of Science, and Google Scholar databases and reference lists of hand-searched articles were searched for published studies from February 2000 to November 2018. The selection criteria were as follows: randomized or quasi-randomized trials that compared the effects of vitamin D or related compounds, alone or with calcium, on vaginal health (growth and differentiation of epithelial cells, dryness, acidity [pH]) outcomes in menopausal women. The methodological quality of these studies was examined using the Cochrane tool checklist by two independent investigators, following which the data were extracted. Of six examined studies, two showed that vitamin D administration improved the growth and differentiation of vaginal epithelial cells, improved vaginal pH, and decreased vaginal dryness in menopausal women. Although the level of evidence for the effects of vitamin D on vaginal health is low in our study, we concluded that vitamin D may improve the vaginal health of women, especially during menopause.
... Это подтверждается экспрессией его рецептора в яичниках, эндометрии, плаценте и гипофизе [3]. Отмечается повышение экспрессии рецепторов витамина D (VDR) в матке у женщин в постменопаузе [4][5]. ...
Article
Full-text available
This literature review summarizes data on the physiological role of vitamin D in women during menopause. We discuss the peculiarities of climacteric syndrome affected by vitamin D deficiency, including the impact of the vitamin on the central nervous system and its role in cognitive and affective disorders. The necessity of vitamin D therapy to prevent pathologies associated with menopause is highlighted.
... 2004, a study was published reporting on the immunohistochemical detection of the vitamin D receptor in rat vaginal epithelium [83]. These results were confirmed in the human vagina by Kim et al., reporting on the presence of the VDR in all layers of the vaginal epithelium [84]. The expression of the vitamin D receptor is upregulated by vitamin D but seems not to correlate with the menstrual cycle. ...
Article
Full-text available
In recent years, a vast amount of studies have centered on the role of vitamin D in the pathogenesis of certain types of cancers such as breast, colorectal and lung cancer. Increasing evidence suggests that vitamin D and its receptor play a crucial role in the development of gynecological cancers. In this review, we systematically analyzed the effect of vitamin D and the vitamin D receptor on endometrial, ovarian, cervical, vulvar and vaginal cancer. Our literature research shows that vitamin D levels and vitamin-D-related pathways affect the risk of gynecological cancers. Numerous ecological studies give evidence on the inverse relationship between UVB exposure and gynecological cancer risk. However, epidemiologic research is still inconclusive for endometrial and ovarian cancer and insufficient for rarer types of gynecological cancers. The vitamin D receptor (VDR) is upregulated in all gynecological cancers, indicating its influence on cancer etiology. The VDR polymorphism FokI (rs2228570) seems to increase the risk of ovarian cancer. Other nuclear receptors, such as the RXR, also influence gynecological cancers. Although there is limited knowledge on the role of the VDR/RXR on the survival of endometrial, cervical, vulvar or vaginal cancer patients, some studies showed that both receptors influence survival. Therefore, we suggest that further studies should focus on the vitamin D- and its hetero dimer receptor RXR in gynecological cancers.
... In an animal model where menopause was induced, vitamin D increased the appearance of protein cornifin beta and induced the increase of vaginal epithelium (Abban et al., 2008). In addition, the researchers reported in the previous study that the appearance of vitamin D receptor, estrogen receptor, and ezrin in premenopausal vaginal epithelium, but there has been no direct molecular study on vitamin D and vagina (Kim et al., 2014). Vitamin D regulates Ezrin protein; one of the components of Moesin/Ezrin/Radixin/Merlin (MERM) proteins (Abban et al., 2008). ...
Article
Full-text available
Postmenopausal atrophic vagina (PAV) is the thinning of the walls of the vagina and decreased lugae of the vagina. PAV is caused by decreased estrogen levels in postmenopausal women. However, the harmful effects of hormone replacement therapy (HRT) have resulted in considerable caution in its use. Various estrogen agonist treatment options are available. Vitamin D is influences the regulation of differentiation and proliferation of various cells, especially tissues lining stratified squamous epithelium, such as the vaginal epithelium. In this study, we hypothesized that vitamin D could provide an alternative and a safe treatment option for PAV by promoting the proliferation and differentiation of the vaginal epithelium. Thirty six patients were enrolled in this case-control study. Vitamin D associated proteins in a vitamin D and sex hormone treated vaginal epithelial cell line as well as normal and PAV tissues were measured. To confirm of cell-to-cell junction protein expression, cell line and tissue studies included RTPCR, immunohistochemistry staining, and immunoblot analyses. The expression of cell-to-cell junction proteins was higher in women with symptoms of atrophic vagina tissue compared to women without the symptoms. Vitamin D stimulated the proliferation of the vaginal epithelium by activating p- RhoA and Erzin through the vitamin D receptor (VDR). The results suggest that vitamin D positively regulates cell-to-cell junction by increasing the VDR/p-RhoA/p-Ezrin pathway. This is the first study to verify the relationship of the expression of RhoA and Ezrin proteins in vaginal tissue of PAV.
Article
Full-text available
Menopause is the time at which menstruation stops in women. After menopause, women are more susceptible to some diseases, especially osteoporosis and cardiovascular disease. Vitamin D has a protective effect against osteoporosis by facilitating the absorption of calcium and affecting parathyroid hormone. Vitamin D also affects cardiovascular function by lowering the blood pressure, which affects the renin–angiotensin system and alters the low-density lipoprotein receptor activity. This paper discusses supplemental vitamin D in postmenopausal women with osteoporosis and cardiovascular disease.
Article
Menopause is the time at which menstruation stops in women. After menopause, women are more susceptible to some diseases, especially osteoporosis and cardiovascular disease. Vitamin D has a protective effect against osteoporosis by facilitating the absorption of calcium and affecting parathyroid hormone. Vitamin D also affects cardiovascular function by lowering the blood pressure, which affects the renin–angiotensin system and alters the low-density lipoprotein receptor activity. This paper discusses supplemental vitamin D in postmenopausal women with osteoporosis and cardiovascular disease.