Estriol

Estriol is an antagonist of the G-protein coupled estrogen receptor in estrogen receptor-negative breast cancer cells.

[Effect of Escherichia coli secreted metabolites on functional activity of human neutrophils against the background of estriol effect].[Pubmed:25536774]

Zh Mikrobiol Epidemiol Immunobiol. 2014 Sep-Oct;(5):65-70.

AIM: Study the effect of Escherichia coli acellular metabolites of various phases of development on phagocytic activity of neutrophils against the background of pregnancy hormone effect--Estriol (E3). MATERIALS AND METHODS: E. coli K12 (wt) metabolites were selected at the end of adaptation and logarithmic growth phases by filtration after cultivation at 37 degrees C in LB broth. Neutrophils of heparinized venous blood of healthy non-pregnant women (follicular phase, n = 8) were incubated for 1 hour with E3 at 2 ng/ml and 20 ng/ml, then 30 minutes with E. coli metabolites, LB medium or Hanks' solution at 37 degrees C. Phagocytic activity evaluation was carried out by inhibition of bioluminescence of E. coli K12 TG1 lux+. RESULTS: Exometabolites of logarithmic growth phase of E. coli culture inhibited neutrophil phagocytosis after 40 - 60 minutes of incubation in contrast to metabolites of adaptation phase compared with LB medium. Neutrophil cultivation after hormone treatment in LB medium that has the ability to stimulate neutrophil phagocytosis compared with Hanks' solution did not alter their phagocytic activity. However inhibiting effect of E3 at 20 ng/ml on neutrophil phagocytosis compared with control was exhibited in Hanks' solution (at 50 - 60 minutes) and after the effect of E. coli adaptation phase metabolites (at 40 - 60 minutes). CONCLUSION: E3 at the level extrapolated from its level at III trimester of pregnancy could facilitate the reduction of antimicrobial potential of neutrophils at the early stages of growth of pathogenic microorganisms.

Single measurement of salivary estriol as a predictor of preterm birth.[Pubmed:26031009]

Pak J Biol Sci. 2014 May;17(5):730-4.

One of the major problems in obstetrics and pediatrics is preterm birth. A new method of prediction of preterm birth is by salivary Estriol. This study aimed to determine the predictive value of single measurement of salivary Estriol and its relationship with preterm birth. In this study, the salivary specimens of 466 pregnant women of 25-34 weeks gestational age were collected and kept in a freezer until delivery. Consequently, the salivary specimens were thawed and Estriol levels were measured. The cut-off point for Estriol was determined by a receiver operating characteristics curve. Salivary Estriol levels equal to or higher than the cut-off point (2.6 ng m(-1)) were considered as the Estriol (+) group and those lower than 2.6 ng mL(-1) were considered as the Estriol (-) group. Our findings showed that 36 (18.3%) subjects in the Estriol (+) group and 22 (8.2%) subjects in the Estriol (-) group had preterm deliveries. There was a significant relationship between salivary Estriol levels and preterm birth (chi2 = 10.636, p = 0.001). Sensitivity, specificity and predictive values (positive and negative) of Estriol were 62, 60, 18.3 and 82%, respectively. Single measurement of salivary Estriol at 25-34 weeks of gestation, with its high negative predictive values, could be beneficial to identify women who will not develop preterm labor. This outcome suggests that unnecessary interventions should be avoided to prevent preterm births.

Effects of estriol on growth, gene expression and estrogen response element activation in human breast cancer cell lines.[Pubmed:24529907]

Maturitas. 2014 Apr;77(4):336-43.

OBJECTIVE: Local application of estradiol (E2) to treat vulvovaginal atrophy in postmenopausal breast cancer patients receiving aromatase inhibitors is known to elevate serum estradiol levels and thereby might counteract breast cancer therapy. Thus, vaginal application of Estriol (E3) has been recommended for these patients. However, it is unclear to what extent E3 stimulates breast cancer cell growth. In this study, we examined the effect of E3 on growth and gene expression of two human breast cancer cell lines. METHODS: We used an established in vitro cell culture assay and compared the effect of E2 and E3 on growth of the estrogen receptor alpha-positive breast cancer cell lines MCF-7 and T-47D testing a wide range of hormone concentrations of 10(-12)-10(-7)M. E3 effects on gene expression were examined by means of reporter gene assays, RT-qPCR and Western blot analysis. RESULTS: E3 acted as a potent estrogen and exerted a mitogenic effect on T-47D and MCF-7 cells at concentrations of 10(-9)M (288 pg/ml) and higher. With regard to activation of an estrogen response element (ERE) in breast cancer cells, effects of E3 were visible at 10(-10)M. The same concentrations of E3 activated expression of the estrogen-responsive gene PR and of the proliferation genes cyclin A2, cyclin B1, Ki-67, c-myc and b-myb, providing molecular mechanisms underlying the observed growth increase. CONCLUSIONS: Like E2, low levels of E3 were able to trigger a robust estrogenic response in breast cancer cells. Thus, our data suggest caution regarding use of E3 by breast cancer survivors.

Estriol blunts postprandial blood glucose rise in male rats through regulating intestinal glucose transporters.[Pubmed:25516546]

Am J Physiol Endocrinol Metab. 2015 Mar 1;308(5):E370-9.

Despite increased total food intake in healthy, late-stage pregnant women, their peak postprandial blood sugar levels are normally much lower than the levels seen in healthy nonpregnant women. In this study, we sought to determine whether Estriol (E3), an endogenous estrogen predominantly produced during human pregnancy, contributes to the regulation of the postprandial blood glucose level in healthy normal rats. In vivo studies using rats showed that E3 blunted the speed and magnitude of the blood glucose rise following oral glucose administration, but it did not appear to affect the total amount of glucose absorbed. E3 also did not affect insulin secretion, but it significantly reduced the rate of intestinal glucose transport compared with vehicle-treated animals. Consistent with this finding, expression of the sodium-dependent glucose transporter 1 and 2 was significantly downregulated by E3 treatment in the brush-border membrane and basolateral membrane, respectively, of enterocytes. Most of the observed in vivo effects were noticeably stronger with E3 than with 17beta-estradiol. Using differentiated human Caco-2 enterocyte monolayer culture as an in vitro model, we confirmed that E3 at physiologically relevant concentrations could directly inhibit glucose uptake via suppression of glucose transporter 2 expression, whereas 17beta-estradiol did not have a similar effect. Collectively, these data showed that E3 can blunt the postprandial glycemic surge in rats through modulating the level of intestinal glucose transporters.