The effects of 17β-estradiol on blood brain barrier integrity in the absence of the estrogen receptor alpha; an in-vitro model

Kuruca, Serap Erdem; Karadenizli, Sabriye; Akgün-Dar, Kadriye; Kapucu, Ayşegül; Kaptan, Zulal; Üzüm, Gülay

doi:10.1016/j.acthis.2017.07.005

Cited by 20 publications

(11 citation statements)

References 49 publications

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“…The associations between plasma LPS levels and progesterone suggest that female sex hormones may play a role in regulating mucosal permeability. In addition, estradiol and human chorionic gonadotropin (hCG) may have an effect on mucosal permeability, and subsequently ignite an elevated microbial translocation and systemic Inflammation (Herr et al 2013, Kuruca et al 2017, Zhou et al 2017). However, our results imply that progesterone may have the opposite effect as estrogen and hCG on mucosal permeability and microbial translocation during pregnancy, but need further investigation.…”

Section: Resultsmentioning

confidence: 99%

Elevated systemic microbial translocation in pregnant HIV-infected women compared to HIV-uninfected women, and its inverse correlations with plasma progesterone levels

Zhou

Powell

Ramakrishnan

et al. 2018

Journal of Reproductive Immunology

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In HIV infection, increased adverse perinatal outcomes reported among HIV-associated pregnancies are not fully understood. Currently, microbial product translocation (MT) from a permeable mucosa is demonstrated as a driver of inflammation, and may contribute to preterm delivery in HIV. Here, our results showed that plasma LPS levels (a representative marker of MT) were increased in HIV-infected women in the first and second trimester. Progesterone levels were significantly decreased in HIV-infected subjects in the first trimester and second trimester. There were significant inverse correlations between plasma LPS and progesterone in the first and second trimester. These results suggested heightened systemic MT and decreased plasma progesterone levels in HIV-infected pregnant women may play a role in increased incidence of preterm delivery.

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Section: Resultsmentioning

confidence: 99%

Elevated systemic microbial translocation in pregnant HIV-infected women compared to HIV-uninfected women, and its inverse correlations with plasma progesterone levels

Zhou

Powell

Ramakrishnan

et al. 2018

Journal of Reproductive Immunology

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“…Estradiol and estriol are two key pregnancy-associated hormones 47 . In addition, estrogen may have an effect on mucosal permeability, and subsequently ignite elevated microbial translocation and systemic inflammation 29,48 . In this study, the increased ratios of estradiol/progesterone and estriol/progesterone at visit 2 and 3 may be the reason why we found no significant correlations between LPS, TNF-α and progesterone in these two visits.…”

Section: Discussionmentioning

confidence: 99%

Progesterone decreases gut permeability through upregulating occludin expression in primary human gut tissues and Caco-2 cells

Zhou

Bian

Luo

et al. 2019

Sci Rep

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Progesterone plays a protective role in preventing inflammation and preterm delivery during pregnancy. However, the mechanism involved is unknown. Microbial product translocation from a permeable mucosa is demonstrated as a driver of inflammation. To study the mechanism of the protective role of progesterone during pregnancy, we investigated the effect of physiologic concentrations of progesterone on tight junction protein occludin expression and human gut permeability in vitro and systemic microbial translocation in pregnant women in vivo . Plasma bacterial lipopolysaccharide (LPS), a representative marker of in vivo systemic microbial translocation was measured. We found that plasma LPS levels were significantly decreased during 24 to 28 weeks of gestation compared to 8 to 12 weeks of gestation. Moreover, plasma LPS levels were negatively correlated with plasma progesterone levels but positively correlated with plasma tumor necrosis factor-alpha (TNF-α) levels at 8 to 12 weeks of gestation but not at 24 to 28 weeks of gestation. Progesterone treatment increased intestinal trans-epithelial electrical resistance (TEER) in primary human colon tissues and Caco-2 cells in vitro through upregulating tight junction protein occludin expression. Furthermore, progesterone exhibited an inhibitory effect on nuclear factor kappa B (NF-κB) activation following LPS stimulation in Caco-2 cells. These results reveal a novel mechanism that progesterone may play an important role in decreasing mucosal permeability, systemic microbial translocation, and inflammation during pregnancy.

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“…This conundrum will only be resolved by future studies examining the effects of central manipulations of sex hormone receptors on the neurochemical systems known to drive sympathetic activity in HF. To fairly assess the effects of sex hormones and their receptors in the HF setting, such studies should be conducted in animals with intact gonads, since the circulating levels of sex steroids can affect both the integrity of the blood-brain barrier (33,35) and the expression of ERs (53) and ARs (8) in brain tissue.…”

Section: Perspectivesmentioning

confidence: 99%

Sex differences in the central and peripheral manifestations of ischemia-induced heart failure in rats

Wei

Weiß

et al. 2019

American Journal of Physiology-Heart and Circulatory Physiology

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Heart failure (HF) is a leading cause of morbidity and mortality for both men and women. Increased sympathetic nerve activity (SNA) is a hallmark of HF and correlates with poor prognosis. We and others have demonstrated that neuroinflammation and renin‐angiotensin system activity are elevated in the cardiovascular‐related regions of the brain in HF, contributing to SNA and the progression of HF. However, most studies that have examined these sympathoexcitatory mediators in the brain in HF have been performed in male animals. The goal of this study was to determine whether sex differences exist in neuroinflammation and renin‐angiotensin system activity in the hypothalamic paraventricular nucleus (PVN), a key cardiovascular‐related center of the brain that regulates SNA and extracellular fluid volume, in rats with HF. Male and female SD rats at ~13 weeks of age underwent coronary artery ligation (CL) to induce HF and were euthanized for anatomical and molecular studies 4 weeks later. Age‐matched male and female rats served as controls. There were no differences between male and female rats in echocardiography‐defined ischemic zone or left ventricular ejection fraction at 24 hours and at 4 weeks after CL. Female rats had lower body weight than male rats, but there was no difference in body weight between HF and control rats in either sex. At 4 weeks, lung weight was similar but right ventricular (RV) and left ventricular (LV) weights were smaller in female control than male control rats. Compared with their respective controls, male HF but not female HF rats had increases in lung weight/tibial length and RV weight/tibial length. There was no difference in LV dP/dtmax and LV end‐diastolic pressure between male and female controls. LV dP/dtmax was decreased in both male HF rats and female HF rats, but male HF rats had a lower dP/dtmax. Compared with their respective control rats, male but not female HF rats had increased LV end‐diastolic pressure. In the PVN, mRNA for tumor necrosis factor‐α (TNF‐α), interleukin‐1β (IL‐1β), angiotensin receptor subtype 1a receptor (AT1aR) and estrogen receptors α and β (ER‐α, ER‐β) was similar in male and female controls. mRNA for G protein‐coupled estrogen receptor (GPER) was higher and mRNA for arginine vasopressin (AVP) was lower in female control than male control rats. Both male HF and female HF rats had increases in TNF‐α, IL‐1β, AT1aR and AVP mRNA in the PVN, compared with their respective controls, but the levels were higher in the male HF rats. ER‐α and ER‐β mRNA was decreased and GPER mRNA was unchanged in male HF and female HF rats, compared with respective controls. There was no difference in ERK1/2 activity in the PVN between male and female control rats, and ERK1/2 activity in the PVN was equally increased in both male and female HF rats. Plasma angiotensin II, AVP and norepinephrine levels were similar in male and female control rats. The plasma levels of these humoral factors were higher in HF rats in either sex, but the AVP and norepinephrine levels were greater in ma...

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The effects of 17β-estradiol on blood brain barrier integrity in the absence of the estrogen receptor alpha; an in-vitro model

Cited by 20 publications

References 49 publications

Elevated systemic microbial translocation in pregnant HIV-infected women compared to HIV-uninfected women, and its inverse correlations with plasma progesterone levels

Elevated systemic microbial translocation in pregnant HIV-infected women compared to HIV-uninfected women, and its inverse correlations with plasma progesterone levels

Progesterone decreases gut permeability through upregulating occludin expression in primary human gut tissues and Caco-2 cells

Sex differences in the central and peripheral manifestations of ischemia-induced heart failure in rats

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