Dietary Intake of 17α-Ethinylestradiol Promotes HCC Progression in Humanized Male Mice Expressing Sex Hormone-Binding Globulin

Hepatocellular carcinoma (HCC) is a male-oriented malignancy; its progression is affected by sex hormones. 17α-ethinylestradiol (EE2) is a synthetic estrogen widely used as an oral contraceptive; however, it is unknown whether EE2 regulates sex hormone action in HCC. We investigated whether EE2 influences HCC risk in male androgenic environments, using mice expressing human sex hormone-binding globulin (SHBG). Two-week-old male mice were injected with diethyl-nitrosamine (DEN, 25 mg/kg) and fed an EE2 diet for 10 weeks from 30 weeks of age. Development and characteristics of liver cancer were evaluated in 40-week-old mice via molecular and histological analyses. Although EE2 did not increase HCC progression in wild-type mice, SHBG mice exhibited remarkably higher HCC risk when fed EE2. The livers of EE2-treated SHBG mice exhibited substantially increased pro-inflammatory necrosis with high plasma levels of ALT and HMGB1, and intrahepatic injury and fibers. Additionally, increased androgen response and androgen-mediated proliferation in the livers of EE2-treated SHBG mice and EE2-exposed hepatocytes under SHBG conditions were observed. As a competitor of SHBG-androgen binding, EE2 could bind with SHBG and increase the bioavailability of androgen. Our results revealed that EE2 is a novel risk factor in androgen-dominant men, predisposing them to HCC risk.

The Effect of a Synthetic Estrogen, Ethinylestradiol, on the hERG Block by E-4031

Inhibition of K+-conductance through the human ether-a-go-go related gene (hERG) channel leads to QT prolongation and is associated with cardiac arrhythmias. We previously reported that physiological concentrations of some estrogens partially suppress the hERG channel currents by interacting with the S6 residue F656 and increase the sensitivity of hERG blockade by E-4031. Although these studies suggested that clinically used synthetic estrogens with similar structures have the marked potential to alter hERG functions, the hERG interactions with synthetic estrogens have not been assessed. We therefore examined whether ethinylestradiol (EE2), a synthetic estrogen used in oral contraceptives, affects hERG function and blockade by drugs. Supratherapeutic concentrations of EE2 did not alter amplitudes or kinetics of the hERG currents elicited by train pulses at 20 mV (0.1 Hz). On the other hand, EE2 at therapeutic concentrations reduced the degree of hERG current suppression by E-4031. The administration of EE2 followed by E-4031 blockade reversed the current suppression, suggesting that the interaction of EE2 and E-4031 alters hERG at the drug-binding site. The effects of EE2 on hERG blockade raised the possibility that other estrogens, including synthetic estrogens, can alter hERG blockade by drugs that cause QT prolongation and ventricular arrhythmias.

Alternative possibilities of hyaluronic acid in genitourinary symptoms treatment

Research objective: to evaluate the clinical efficacy of vaginal gel with hyaluronic acid Revitaxa gel in comparison with synthetic estrogen-like topical agent in the treatment of women with genitourinary syndrome, to determine the recurrence rate of atrophic changes as a result of these schemes.Materials and methods. The study included 60 women with genitourinary manifestations and atrophic changes of the vaginal mucosa and cervical epithelium. Clinical, cytological and colposcopic studies were performed to analyze the vaginal epithelium, vaginal microbiocenosis and vaginal tissues. All women with an inflammatory type of smear were prescribed vaginal rehabilitation before the study. Repeated laboratory examination after anti-inflammatory, antibacterial topical therapy confirmed no pathogenic microflora, but signs of atrophy persisted in all women. All women are prescribed local treatment to improve the reparative processes of the vaginal mucosa. The main group (30 women) used Revitaxa gel for local therapy; the control group (30 women) used vaginal suppositories with the synthetic estrogen-like agent promestrienum.Results. Cytological remission after treatment was observed in all women of the control group and in 76.7% of patients in the main group. Restoration of the vaginal mucosa was detected in all patients of the control group and in 90% of patients in the main group. Repeated examinations 4 months after the end of therapy determined no recurrence of atrophic colpitis in 53.3% of patients in the main group and in 30% of women in the control group. Preservation of a favorable estatrophic type of smears was observed in 43.3% of women of group I and 13.3% of patients of group II (p <0.05), which indicates a more stable effect of hyaluronic acid compared with estrogen-like agent.Conclusions. Vaginal gel with hyaluronic acid Revitaxa gel in women with genitourinary syndrome gives results similar to the synthetic estrogen-like drug with promestrienum for topical treatment according to colposcopy, cytology, hormonal colpocytology and clinical indicators. Therefore, Revitaxa gel may be recommended for effective use in women with atrophic colpitis who refuse or have contraindications for topical hormonal agents.

Natural and Synthetic Estrogens Regulate Human Health

Estrogen are very important chemical compounds very essential for our body functions. The cholesterol, what we eat through food, gets converted by the action of various enzymes. Scientists have synthesized estrogenic molecules in the laboratory and used them for oral contraceptives and other therapeutic purposes. Environmental estrogenic molecules (xenestrogen) played havocs in human life. Plants also make estrogenic substances (phytoestrogen); they are very useful for mankind. All steroid hormones, including estrogen are synthesized from cholesterol through a common precursor steroid, pregnenolone which is formed by the enzymatic cleavage of a 6-carbon side-chain of the 27-carbon cholesterol molecule. Cholesterol is a starting substance of group of estrogenic compounds [1]. On the other hand, synthetic estrogen are compounds obtained by chemical synthesis that possess estrogenic activity [2]. In addition to these estrogenic compounds there are some estrogenic action mimicking compounds known as xenestrogen and phytoestrogen (Figure 1).

Detection of Estrogenic Hormones Using Plasmonic Nanostructures

<div> <div> <div> <p>By optimising the geometry of asymmetric split-H (ASH) resonators fabricated on zinc selenide, we have produced a total of four distinct plasmonic resonances that could be matched with six molecular vibration wavelengths (for O-H, C-H, C=O, C=C, CºC-H and C-C bonds) which are relevant to the detection of four estrogenic hormones: estrone (E1), 17β-estradiol (E2), estriol (E3) and synthetic estrogen; 17α-ethinyl estradiol (EE2). Specifically, sensitivities of 363 nm/RIU and 636 nm/RIU were achieved from the deposition of E2 on ASH1 (2 μm and 4 μm) and ASH2 (5 μm and 8 μm) respectively. A Fourier transform infrared (FTIR) spectrometer was used to measure the transmittance resonances of the fabricated ASH arrays. The amplitudes of the molecular vibrational resonances were also around 500 times greater when matched with the plasmonic resonances of the ASHs as compared with deposit on on bulk ZnSe substrates. Finally, when mixtures of two hormones were deposited on the nanoantennas, the molar ratio for each of the hormones could also be calculated by using the peak intensities for the different molecular vibration wavelengths. By engineering the spectral response of ASH resonators to match specific estrogenic fingerprints, the work paves the way for the development of metamaterial sensors with better specificity and enhanced functionalities.</p> </div> </div> </div>