Structural analysis of estrogen receptors: interaction between estrogen receptors and cav-1 within the caveolae†.

Pregnancy is a physiologic state of substantially elevated estrogen biosynthesis that maintains vasodilator production by uterine artery endothelial cells (P-UAECs) and thus uterine perfusion. Estrogen receptors (ER-α and ER-β; ESR1 and ESR2) stimulate nongenomic rapid vasodilatory responses partly through activation of endothelial nitric oxide synthase (eNOS). Rapid estrogenic responses are initiated by the ∼4% ESRs localized to the plasmalemma of endothelial cells.

Effects of the Catechol and Methoxy Metabolites of 17β-Estradiol on Nitric Oxide Production by Ovine Uterine Artery Endothelial Cells.

Nitric oxide (NO) production is essential to facilitate rises in uterine blood flow (UBF) during pregnancy. It has been proposed that the metabolites of Eβ, 2-hydroxyestradiol (2-OHE), 4-hydroxyestradiol (4-OHE), 2-methoxyestradiol (2-ME), and 4-methoxyestradiol (4-ME) play a role in mediating vasodilation and rises in UBF during pregnancy. We previously showed that the Eβ metabolites stimulate prostacyclin production in pregnancy-derived ovine uterine artery endothelial cells (P-UAECs); however, it is unknown whether the Eβ metabolites also induce NO production.

Convergent ERK1/2, p38 and JNK mitogen activated protein kinases (MAPKs) signalling mediate catecholoestradiol-induced proliferation of ovine uterine artery endothelial cells.

Key Points: The catechol metabolites of 17β-oestradiol (E β), 2-hydroxyoestradiol (2-OHE ) and 4-hydroxyoestradiol (4-OHE ), stimulate proliferation of pregnancy-derived ovine uterine artery endothelial cells (P-UAECs) through β-adrenoceptors (β-ARs) and independently of the classic oestrogen receptors (ERs). Herein we show that activation of ERK1/2, p38 and JNK mitogen activated protein kinases (MAPKs) is necessary for 2-OHE - and 4-OHE -induced P-UAEC proliferation, as well as proliferation induced by the parent hormone E β and other β-AR signalling hormones (i.e.