The effects of estrogen on the α2-adrenergic receptor subtypes in rat uterine function in late pregnancy in vitro.
OBJECTIVE
To assess the effect of 17β-estradiol pretreatment on the function and expression of α2- adrenergic receptors (ARs) subtypes in late pregnancy in rats.


METHODS
Sprague-Dawley rats (n=37) were treated with 17β-estradiol for 4 days starting from the 18th day of pregnancy. The myometrial expression of the α2-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 (α2A), ARC 239 (α2B/C), and spiroxatrine (α2A). 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 α2-ARs, and abolished the contractile effect via the α2B-ARs. All the α2-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 α2-AR subtypes is sensitive to 17β-estradiol, which decreases the contractile response of (-)-noradrenaline via the α2B-AR subtype, and might cause changes in G-protein signaling pathway. Estrogen dysregulation may be responsible for preterm labor or uterine inertia via the α2-ARs.
Judit
J
Hajagos-Toth
Judit
J
Bota
Eszter
E
Ducza
Adrienn
A
Csanyi
Zita
Z
Tiszai
Anna
A
Borsodi
Reza
R
Samavati
Sandor
S
Benyhe
Robert Gaspar, Szeged, H-6701, P.O. Box 121, Hungary, gaspar@pharm.u-szeged.hu.
Robert
R
Gaspar
D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D008297:Male; D007752:Obstetric Labor, Premature / Q000503:physiopathology*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D014590:Uterine Contraction / Q000187:drug effects
D058669:Adrenergic alpha-2 Receptor Antagonists; D018341:Receptors, Adrenergic, alpha-2; D004958:Estradiol