The Role of Estriol and Estrone in Keratoconic Stromal Sex Hormone Receptors

Keratoconus (KC) is a progressive corneal thinning disease that manifests in puberty and worsens during pregnancy. KC onset and progression are attributed to diverse factors that include: environmental, genetics, and hormonal imbalances; however, the pathobiology remains elusive. This study aims to determine the role of corneal stroma sex hormone receptors in KC and their interplay with estrone (E1) and estriol (E3) using our established 3D in vitro model. Healthy cornea stromal cells (HCFs) and KC cornea stromal cells (HKCs), both male and female, were stimulated with various concentrations of E1 and E3. Significant changes were observed between cell types, as well as between males and females in the sex hormone receptors tested; androgen receptor (AR), progesterone receptor (PR), estrogen receptor alpha (ERα), and estrogen receptor beta (ERβ) using Western blot analysis. E1 and E3 stimulations in HCF females showed AR, PR, and ERβ were significantly upregulated compared to HCF males.
In contrast, ERα and ERβ had significantly higher expression in HKC’s females than HKC’s males. Our data suggest that the human cornea is a sex-dependent, hormone-responsive tissue that is significantly influenced by E1 and E3. Therefore, it is plausible that E1, E3, and sex hormone receptors are involved in the KC pathobiology, warranting further investigation.

Compatibility of Estradiol, Estriol, Estrone, Progesterone, and Testosterone Single Formulation in Fitalite, Versatile, or HRT Supreme Cream Base

In this work, we focus on three ready-to-use vehicles: Fitalite, Versatile, and HRT Supreme Cream Base. Fitalite is a natural, light, hydrophilic gel-cream that contains vitamin E and oil bodies from plant sources (phytosomes), providing antioxidant and skinmoisturizing properties. Versatile is a vanishing oil-inwater cream base which retains its consistency with a broad range and high concentrations of active pharmaceutical ingredients, dermaceutical ingredients, and solvents. Finally, HRT Supreme Cream Base is a paraben-free, dye-free, fragrance-free O/W emulsion base, formulated with a complex of botanical oils to soothe and provide moisture to dry and sensitive skin. In the current study, we evaluated the beyond-use date of formulations containing estradiol, estriol, estrone, progesterone, and testosterone in combination, compounded with these three vehicles.
Validated, stability-indicating high-performance liquid chromatography methods were used throughout a 180-day period. A beyond-use date of 180 days was observed for all vehicles stored both at refrigerated and at room temperature. The combination of five ingredients represents a worst-case scenario since there are more possibilities of cross reactions. Therefore, we expect the same or greater stability as individual ingredients are removed from the tested formulation. The extended beyond-use dates provide convenience for both the compounding pharmacist and the patient.

A technical and clinical evaluation of the new ThermoFisher BRAHMS unconjugated estriol and inhibin-A assays and their use in second trimester Down syndrome screening

To evaluate second-trimester Down syndrome screening performance of the new ThermoFisher BRAHMS GOLD unconjugated estriol (uE3) and inhibin-A assays. Serum samples were analyzed for levels of uE3 and inhibin-A using the ThermoFisher BRAHMS GOLD immunoanalyzer and compared to other platforms. Levels were transformed to multiples of the median (MoM) in unaffected pregnancies. Log10 MoM distributions in unaffected and Down syndrome pregnancies were assessed for central tendency (mean) and dispersion (SD). Empirical and estimated screening performances were determined. Correlation between BRAHMS and AutoDELFIA® uE3 and inhibin-A were 0.63 and 0.97, respectively, the respective mean difference was 31.3% [95%CI 50.2% to -112.8%] and -23.3% [95%CI -41.9% to -4.7%]. Passing-Bablok indicated significant systematic (-2.78 [95%CI -3.57 to -2.04]) and proportional bias (1.30 [95%CI 1.15 to -1.47]) between uE3 assays and significant proportional bias (0.71[95%CI 0.65-0.78]) between inhibin-A assays.
The uE3 and inhibin-A log10 MoM distribution mean [SD] in unaffected and Down syndrome pregnancies were 0.0024 [SD = 0.2341] and -0.0001 [SD = 0.2078], and -0.2028 [SD = 0.2495] and 0.3645 [SD = 0.2576], respectively. The new BRAHMS uE3 and inhibin-A assays had an 81-83% detection rate for Trisomy21 for a 5% false-positive rate. The new BRAHMS assays achieved the expected screening performance provided the risk estimation model is adjusted to account for the higher BRAHMS uE3 MoM measurement distribution variance.

Estriol dissolving microneedle patches for protection against ionizing radiation-induced injury

Estriol can be used to treat radiation-induced leukopenia by increasing peripheral blood leukocytes and therefore it plays an important role in radiation protection. However, only high-dose injectable suspensions are available when estriol is used to combat against ionizing radiation-induced injury. Intramuscular (i.m.) administration of estriol is very painful and inconvenient, and the lack of timely self-administered formulation greatly limits the wide application of estriol. This will facilitate quick response under emergent conditions in complementary with the available estriol formulations. Herein, we prepared estriol microneedle (MNs) patches for the convenient and efficient treatment of radiation-induced injury.
A biocompatible polymer, polyvinylpyrrolidone K90, was dissolved in an estriol solution of methanol and cast into a mold to obtain conical-shaped MNs. N-vinyl pyrrolidone was poured on the base of the MNs and photocured to enhance the mechanical strength of estriol MNs (EMNs). EMNs were easily pierced 200 μm into the mouse skin. More importantly, the EMNs tips were dissolved very quickly within 5 min so that the drugs could permeate across skin. Mouse models of ionizing radiation-induced injury were established with 6.5 Gy radiation of 60Co γ ray. Moreover, EMNs increased peripheral blood leukocytes in irradiated mice, protected the bone marrow hematopoietic system, and improved the survival rate of the irradiated mice to 80 %. EMNs are a promising transdermal drug delivery system that allows for easy, rapid administration and protects the body from damage caused by ionizing radiation.

Estradiol

20-abx185851 Abbexa
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GP9683-25 Glentham Life Sciences 25 332.2 EUR

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GP9683-5 Glentham Life Sciences 5 98.8 EUR

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Cortisol and estriol responses to awakening in the first pregnancy trimester: Associations with maternal stress and resilience factors

Background: Little is known about the maternal cortisol awakening response (CAR) in the first pregnancy trimester. Similarly unknown is how the CAR in early gestation relates to other steroid hormones, such as estriol. Maternal estriol in blood and urine is used to monitor fetal well-being since it is produced by the fetoplacental unit from fetal precursors. Low levels have been associated with maternal-fetal complications. We were recently able to show that estriol is measurable in maternal saliva from 6 weeks’ gestation onwards. However, its pattern following morning awakening and potential links with salivary cortisol in early gestation is relatively unknown. In this prospective study, we explored the cortisol and estriol responses to morning awakening in first-trimester pregnant women, the potential association of these endocrine variables with maternal stress and resilience factors, and their predictive value for the further pregnancy course.
Methods: Fifty-one women with an uncomplicated, singleton pregnancy responded to questionnaires measuring chronic and pregnancy-specific stress, emotional support, and daily uplifts at 6 weeks’ gestation. At 8 and 10 weeks, the women collected saliva samples immediately, 30, and 60 min after morning awakening. After 12 weeks, 40 women reported on the further pregnancy course, of whom 6 had developed complications.
Results: In response to morning awakening, cortisol levels increased significantly at 10 weeks (p = .04), while estriol levels decreased significantly at both 8 and 10 weeks (p < .001). A stronger cortisol increase was linked to a stronger estriol decrease at 8 (p = .03), but not at 10 weeks. Then, perceived emotional support at 6 weeks was negatively associated with cortisol baseline at 8 (p = .01) and positively with estriol baseline at 10 weeks (p = .03). Moreover, higher pregnancy-specific stress was related to a lower estriol baseline at 8 weeks (p = .047). Furthermore, compared to healthy women, those with complications at follow-up had already reported less emotional support (p = .03) and fewer daily uplifts (p = .03) at 6 weeks. These women also seemed to lack a significant estriol response to morning awakening at 8 weeks (p > .10).
Discussion: These findings advance our knowledge of cortisol and estriol secretion following morning awakening and encourage the investigation of E3 in addition to cortisol when researching prenatal stress and its consequences for maternal and fetal health.

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