The effects of estrogen on the α2-adrenergic receptor subtypes in rat uterine function in late pregnancy in vitro

Aim To assess the effect of 17 beta-estradiol pretreatment on the function and expression of alpha(2)-adrenergic receptors (ARs) subtypes in late pregnancy in rats. Methods Sprague-Dawley SPD rats (n=37) were treated with 17 beta-estradiol for 4 days starting from the 18th day of pregnancy. The myometrial expression of the alpha(2)-AR subtypes was determined by real time polymerase chain reaction and Western blot analysis. In vitro contractions were stimulated with (-)-noradrenaline, and its effect was modified with the selective antagonists BRL 44408 (alpha(2A)), ARC 239 (alpha(2B/c), and spiroxatrine (alpha(2A)). The cyclic adenosine mono phosphate (cAMP) accumulation was also measured. The activated G-protein level was investigated by guanosine 5'-O-[gamma-thioltriphosphate (GTPyS) binding assay. Results 17 beta-estradiol pretreatment decreased the contractile effect of (-)-noradrenaline via the alpha(2)-ARs, and abolished the contractile effect via the alpha B-2-ARs. All the alpha(2)-AR subtypes' mRNA was significantly decreased. 17 beta-estradiol pretreatment significantly increased the myometrial cAMP level in the presence of BRL 444108 (P=0.001), ARC 239 (P=0.007), and spiroxatrine (P=0.045), but did not modify it in the presence of of spiroxatrine + BRL 44408 combination (P=0.073). It also inhibited the G-protein-activating effect of (-)-noradrenaline by 25% in the presence of BRL 44408 + spiroxatrine combination. Conclusions The expression of the alpha(2)-AR subtypes is sensitive to 17 beta-estradiol, which decreases the contractile response of (-)-noradrenaline via the alpha(28)-AR subtype, and might cause changes in G-protein signaling pathway. Estrogen dysregulation may be responsible for preterm labor or uterine inertia via the alpha(2)-ARs.