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 17β-estradiol pretreatment on the function and expression of α(2)- adrenergic receptors (ARs) subtypes in late pregnancy in rats. METHODS: Sprague-Dawley SPD rats (n = 37) were treated with 17β-estradiol for 4 days starting from the 18th day of pregnancy. The myometrial expression of the α(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 (α(2A)), ARC 239 (α(2B/C)), and spiroxatrine (α(2A)). The cyclic adenosine monophosphate (cAMP) accumulation was also measured. The activated G-protein level was investigated by guanosine 5′-O-[gamma-thio]triphosphate (GTPγS) binding assay. RESULTS: 17β-estradiol pretreatment decreased the contractile effect of (-)-noradrenaline via the α(2)-ARs, and abolished the contractile effect via the α(2B)-ARs. All the α(2)-AR subtypes’ mRNA was significantly decreased. 17β-estradiol pretreatment significantly increased the myometrial cAMP level in the presence of BRL 44408 (P = 0.001), ARC 239 (P = 0.007), and spiroxatrine (P = 0.045), but did not modify it in the presence 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 α(2)-AR subtypes is sensitive to 17β-estradiol, which decreases the contractile response of (-)-noradrenaline via the α(2B)-AR subtype, and might cause changes in G-protein signaling pathway. Estrogen dysregulation may be responsible for preterm labor or uterine inertia via the α(2)-ARs.