Recently, numerous scientific approaches have been explored to treat various diseases using stem cells. In 2006, induced pluripotent stem cell (iPSC) were introduced by Takahashi and Yamanaka and showed the potential of self-renewing and differentiation into all types of targeted cells in vitro. In this investigation, we studied the effect of testosterone (T) individually or in the presence of 17 β-estradiol (E2) on osteogenic differentiation of human iPSC (hiPSC) during 2 wk. The optimal concentrations of sex steroid hormones were examined by MTT assay and acridine orange (AO) staining.
The impact of E2 and T either individually or together as a combination was examined by ALP activity; the content of total mineral calcium, by von Kossa and alizarin red staining. Additionally, the expression rate of osteogenic specific markers was studied via real-time RT-PCR and immunocytochemistry analyses at day 14 of differentiation. The obtained results illustrated that the differentiation medium supplemented with T-E2 increased not only the ALP enzyme activity and the content of calcium but also the osteogenic-related gene and protein expressions on the 14th day. Furthermore, the results were confirmed by mineralized matrix staining. In conclusion, these data suggest that T could be used as an effective factor for osteogenic induction of hiPSCs combined with the E2 in bone regeneration.
Sexual maturity of children on regular hemodialysis: Role of testosterone and estradiol, a tertiary multicenter experience
- A big problem is the delayed growth and sexual maturity in children with chronic kidney disease (CKD) with the consequent reduction in adults’ height. Testosterone and estradiol have significant physiologic changes in children suffering from CKD, resulting in delayed puberty. We aim to assess blood levels of these hormones in patients with CKD-5 on regular hemodialysis.One hundred-six participants were enrolled in the current study, 56 of whom had CKD on hemodialysis 3 times a week 4 hours per session, and 60 healthy age- and gender-matched children acted as controls.
- Full history was taken, and a clinical review was performed on both patients and controls. The pubertal assessment was performed according to Tanner’s classification and laboratory investigations of total and free serum (s.) testosterone in boys and s.estradiol in girls.Patients’ weight and height were considerably lower than controls. The free and total s.testosterone of patients were significantly reduced. The same applies to s.estradiol levels which were substantially reduced in comparison to controls.
- In both patients and controls, Tanner staging & male total s.testosterone levels and female s.estradiol levels had significant positive associations. There was a negative association between the sex hormones levels and the disease’s and dialysis duration in the patients’ group.S.testosterone and s.estradiol levels were significantly low in CKD patients on dialysis and were positively correlated with delayed pubertal growth observed in those patients.
ERα, but not ERβ and GPER, Mediates Estradiol-Induced Secretion of TSH in Mouse Pituitary
Although estradiol (E2) plays a critical role in the promotion of pituitary development and in the regulation of various pituitary hormones, its effects on the thyroid-stimulating hormone (TSH) remain unaddressed. The actions of E2 are mediated by two classical nuclear estrogen receptors α (ERα) and β (ERβ) and the G protein-coupled estrogen receptor (GPER). However, the types of estrogen receptor involvement in the regulation of thyrotropes are still limited. In this study, we demonstrate that ERα, but not ERβ and GPER, is localized to thyrotropes in the pituitary of female mouse.
In agreement with the presence of ERα in thyrotropes, E2 was shown to stimulate TSH release in vitro from primary culture of female mouse pituitary cells. PPT, a ERα-selective agonist, but not DPN (a ERβ-selective agonist) and G-1 (a GPER-selective agonist), was shown to stimulate TSH release in mouse pituitary cells. This effect could be prevented by the specific ER antagonist fulvestrant and the selective ERα antagonist MPP. The findings of this study suggest that E2 may bind to ERα to trigger TSH release and provide novel information on the differential regulation of multiple estrogen receptors in the pituitary.
Melatonin inhibits 17β-estradiol-induced epithelial-mesenchymal transition in endometrial adenocarcinoma cells via upregulating Numb expression
Objectives: Melatonin shows anti-tumor effects in various tumor types, including endometrial carcinoma. However, the molecular mechanism involved is unclear. In the current study, we investigated the effect of melatonin on the estrogen-induced epithelial-mesenchymal transition (EMT) in endometrial adenocarcinoma cells and explored the pathway that might be involved.
Design: Laboratory study via cultured endometrial cancer cells. Design refers only to in vitro experiments.
Methods: In cell culture experiments, cell growth was examined using CCK8 assays. The expression of Numb and EMT markers in Ishikawa cells were examined using western blot analysis and real-time PCR. Cell invasion was examined using transwell assays. Cell migration were examined using wound healing assays and transwell assays. Using immunohistochemistry analysis, the expression of Numb in human endometrial cancers was examined.
Results: In immunohistochemistry experiments, we found that 15.2% of atypical endometrial hyperplasia and 15.6% of endometrial carcinoma did not express Numb. In cell culture experiments, melatonin inhibited cell proliferation, invasion and migration induced by 17β-estradiol in endometrial cancer cells. Melatonin decreased the expression of Vimentin and Slug, increased the expression of Numb and E-cadherin in Ishikawa cells. Numb knockdown in cancer cells significantly increased cell proliferation, invasion, and migration.
Limitations: No animal experiments were performed.
Conclusions: Melatonin blocked 17β-estradiol-induced cell growth and EMT in endometrial cancer cells via upregulating Numb expression.
Estradiol 17b, 6-CMO (Estradiol 6, 17b CMO) |
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| MBS638945-5mg | MyBiosource | 5mg | 855 EUR |
Estradiol 17b, 6-CMO (Estradiol 6, 17b CMO) |
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| MBS638945-5x5mg | MyBiosource | 5x5mg | 3695 EUR |
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| A8425-1000 | ApexBio | 1g | 42 EUR |
Estradiol |
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| A8425-5.1 | ApexBio | 10 mM (in 1mL DMSO) | 40 EUR |
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| A8425-50 | ApexBio | 50 mg | 157.2 EUR |
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| 317788 | MedKoo Biosciences | 500.0mg | 195 EUR |
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| 20-abx185851 | Abbexa |
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| DE2693 | Demeditec Diagnostics | 96 | 84 EUR |
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| E1KS1709 | EnoGene | 100 mg | 151.2 EUR |
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| AT070 | Unibiotest | 1mg | 1641.6 EUR |
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| AG070 | Unibiotest | 1 mg | 627.6 EUR |
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| MBS122090-01mg | MyBiosource | 0.1mg | 220 EUR |
Estradiol |
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| MBS122090-1mg | MyBiosource | 1mg | 350 EUR |
Estradiol |
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| MBS122090-5x1mg | MyBiosource | 5x1mg | 1490 EUR |
Estradiol |
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| MBS122091-01mg | MyBiosource | 0.1mg | 220 EUR |
Estradiol |
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| MBS122091-1mg | MyBiosource | 1mg | 350 EUR |
Estradiol |
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| MBS122091-5x1mg | MyBiosource | 5x1mg | 1490 EUR |
Estradiol |
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| GP9683 | Glentham Life Sciences | 1g | 304.24 EUR |
Estradiol |
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| GWB-2E7E30 | GenWay Biotech | 1 ml | Ask for price |
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| HY-B0141 | MedChemExpress | 500mg | 129.6 EUR |
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| GP9683-1 | Glentham Life Sciences | 1 | 27.8 EUR |
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| GP9683-10 | Glentham Life Sciences | 10 | 172.4 EUR |
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| GP9683-10G | Glentham Life Sciences | 10 g | 244.8 EUR |
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| GP9683-1G | Glentham Life Sciences | 1 g | 69.6 EUR |
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| GP9683-25 | Glentham Life Sciences | 25 | 332.2 EUR |
Estradiol |
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| GP9683-25G | Glentham Life Sciences | 25 g | 438 EUR |
APOE4 homozygotes are resistant to the mnemonic benefits of 17β-estradiol in the EFAD mouse model of Alzheimer’s disease
Background: Loss of circulating estrogens at menopause may contribute to increased risk for Alzheimer’s disease (AD) in females relative to males. APOE4, the greatest genetic risk factor for AD, acts synergistically with estrogens to increase risk in females. However, despite the relative contributions of APOE genotype and estrogen loss to sex differences in AD risk, these factors are rarely examined in concert in basic research. Hence, our knowledge of how APOE genotype may interact with estrogens to contribute to AD risk, or whether estrogens may be of benefit to particular genotypes, is limited.
Method: The present study was designed to test whether APOE genotype interacts with E2 to modulate cognition and dendritic spine density in a mouse model of AD. Effects of 17β-estradiol (E2 ) treatment on memory were examined in ovariectomized (OVXed) transgenic mice expressing 5 familial AD mutations (5XFAD) and two copies of human APOE3 (E3FAD), APOE4 (E4FAD), or one copy each of APOE3/APOE4 (E3/4FAD). OVXed female E3FAD, E3/4FAD, and E4FAD mice received bilateral dorsal hippocampal (DH) infusion of E2 immediately after training in object recognition (OR) and object placement (OP) tasks. Next, the effect of APOE genotype to modulate estrogenic effects on spines was examined. E3FAD, E3/4FAD, and E4FAD mice received DH infusion of E2 and brains were collected for Golgi impregnation and quantification of dendritic spine density 2 h later.
Result: DH infusion of E2 facilitated OR and OP memory in E3FAD and E3/4FADs, but not E4FADs. Similarly, DH infusion of E2 increased CA1 apical dendritic spine density in E3FADs and E3/4FADs, but not E4FADs. CA1 basal spine density was significantly reduced by E4FAD genotype.
Conclusion: The significant benefit of E2 only in E3FAD and E3/4FAD mice suggests that having two copies of the APOE4 allele results in lower susceptibility to the memory-enhancing effects of E2 in the EFAD model. These findings provide novel evidence that E2 may be of clinical benefit to APOE3 and APOE3/4, but not homozygous APOE4, carriers.