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Background  The adrenergic system and progesterone play major roles in the control of the uterine function. Our aims were to clarify the changes in function and expression of the α 2 -adrenergic receptor (AR) subtypes after progesterone pretreatment in late pregnancy.    Methods  Sprague Dawley rats from pregnancy day 15 were treated with progesterone for 7 days. The myometrial expressions of the α 2 -AR subtypes were determined by RT-PCR 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 accumulation of myometrial cAMP was also measured. The activated G-protein level was investigated via GTPγS binding assays.    Results  Progesterone pretreatment decreased the contractile effect of (−)-noradrenaline through the α 2 -ARs. The most significant reduction was found through the α 2B -ARs. The mRNA of all of the α 2 -AR subtypes was increased. Progesterone pretreatment increased the myometrial cAMP level in the presence of BRL 44408 ( p  < 0.001), spiroxatrine ( p  < 0.001) or the spiroxatrine + BRL 44408 combination ( p  < 0.05). Progesterone pretreatment increased the G-protein-activating effect of (−)-noradrenaline in the presence of the spiroxatrine + BRL 44408 combination.    Conclusions  The expression of the α 2 -AR subtypes is progesterone-sensitive. It decreases the contractile response of (−)-noradrenaline through the α 2B -AR subtype, blocks the function of α 2A -AR subtype and alters the G protein coupling of these receptors, promoting a G s -dependent pathway. A combination of α 2C -AR agonists and α 2B -AR antagonists with progesterone could be considered for the treatment or prevention of preterm birth.

The effects of progesterone on the alpha2-adrenergic receptor subtypes in late-pregnant uterine contractions in vitro