17β estradiol là gì? Các công bố khoa học về 17β estradiol

A fraction of the nuclear estrogen receptor α (ERα) is localized to the plasma membrane region of 17β-estradiol (E2) target cells. We previously reported that ERα is a palmitoylated protein. To gain insight into the molecular mechanism of ERα residence at the plasma membrane, we tested both the role of palmitoylation and the impact of E2 stimulation on ERα membrane localization. The cancer cell lines expressing transfected or endogenous human ERα (HeLa and HepG2, respectively) or the ERα nonpalmitoylable Cys447Ala mutant transfected in HeLa cells were used as experimental models. We found that palmitoylation of ERα enacts ERα association with the plasma membrane, interaction with the membrane protein caveolin-1, and nongenomic activities, including activation of signaling pathways and cell proliferation (i.e., ERK and AKT activation, cyclin D₁ promoter activity, DNA synthesis). Moreover, E2 reduces both ERα palmitoylation and its interaction with caveolin-1, in a time- and dose-dependent manner. These data point to the physiological role of ERα palmitoylation in the receptor localization to the cell membrane and in the regulation of the E2-induced cell proliferation.

Females live longer than males. Oestrogens protect females against aging by up‐regulating the expression of antioxidant, longevity‐related genes such as glutathione peroxidase (GPx) and Mn‐superoxide dismutase (Mn‐SOD). The mechanism through which oestrogens up‐regulate those enzymes remains unidentified, but may have implications for gender differences in lifespan. We show that physiological concentrations of oestradiol act through oestrogen receptors to reduce peroxide levels in MCF‐7 cells (a mammary gland tumour cell line). Oestradiol increases MAP kinase (MAPK) activation as indicated by ERK1 and ERK2 phosphorylation in MCF‐7 cells, which in turn activates the nuclear factor kappa B (NFκB) signalling pathways as indicated by an increase in the p50 subunit of NFκB in nuclear extracts. Blockade of MAPK and NFκB signalling reduces the antioxidant effect of oestradiol. Finally, we show that activation of MAPK and NFκB by oestrogens drives the expression of the antioxidant enzymes Mn‐SOD and GPx. We conclude that oestradiol sequentially activates MAPK and NFκB following receptor activation to up‐regulate the expression of antioxidant enzymes, providing a cogent explanation for the antioxidant properties of oestrogen and its effects on longevity‐related genes.

Female reproductive hormones are considered to be protective agents in atherosclerotic vascular disease and stroke. The present study determined if there are unique cerebrovascular responses in female animals to global cerebral ischemia and if 17β-estradiol is important to postischemic outcome in brain. Three groups of anesthetized, sexually mature rabbits were treated with normotensive four-vessel occlusion (6 min) and 3 h of reperfusion: females chronically instrumented with 17β-estradiol implants (EFEM; n = 8, plasma estradiol level = 365 ± 48 pg/ml), untreated females (FEM; n = 8, estradiol = 13 ± 3 pg/ml), and untreated males (M; n = 8, estradiol < limit of radioimmunoassay). CBF (microspheres) and somatosensory evoked potential (SEP) amplitude were measured during ischemia/reperfusion. Baseline hemispheric blood flow and regional flow distribution were not altered by chronic estradiol treatment. Hemispheric blood flow was equivalently reduced during ischemia in FEM and M (6 ± 1 and 9 ± 2 ml min⁻¹ 100 g⁻¹ respectively); however postischemic hyperemia was greater in FEM than M (CBF = 257 ± 27 and 183 ± 27 ml min⁻¹ 100 g⁻¹. However, EFEM experienced higher CBF during ischemia (e.g., 13 ± 2 ml min⁻¹ 100 g⁻¹) and less hyperemia (134 ± 4 ml min⁻¹ 100 g⁻¹ in hemispheres) in numerous brain regions than FEM. CBF at 3 h reperfusion was not different among the groups. Recovery of SEPs was incomplete and similar in all groups. We conclude that chronic exogenous 17β-estradiol treatment increases CBF during global incomplete ischemia and ameliorates postischemic hyperemia in the female animal.