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

Reproductive Biology and Endocrinology

Research

Judit Bóta¹  Róbert Gáspár¹  Eszter Ducza¹  Judit Hajagos-Tóth¹  Reza Samavati²  Sándor Benyhe²  Anna Borsodi² 

[1] Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, P.O. Box 121, H-6701, Szeged, Hungary;Institute of Biochemistry, Biological Research Centre, Hungarian Academy of Sciences, Temesvari krt 62, H-6726, Szeged, Hungary;

关键词: Progesterone;    Gestation;    Rat;    Myometrium;    α-adrenergic receptor subtypes;   

DOI  :  10.1186/s12958-016-0166-9

 received in 2016-04-20, accepted in 2016-06-09,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundThe 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 α2-adrenergic receptor (AR) subtypes after progesterone pretreatment in late pregnancy.MethodsSprague Dawley rats from pregnancy day 15 were treated with progesterone for 7 days. The myometrial expressions of the α2-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 (α2A), ARC 239 (α2B/C) and spiroxatrine (α2A). The accumulation of myometrial cAMP was also measured. The activated G-protein level was investigated via GTPγS binding assays.ResultsProgesterone pretreatment decreased the contractile effect of (−)-noradrenaline through the α2-ARs. The most significant reduction was found through the α2B-ARs. The mRNA of all of the α2-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.ConclusionsThe expression of the α2-AR subtypes is progesterone-sensitive. It decreases the contractile response of (−)-noradrenaline through the α2B-AR subtype, blocks the function of α2A-AR subtype and alters the G protein coupling of these receptors, promoting a Gs-dependent pathway. A combination of α2C-AR agonists and α2B-AR antagonists with progesterone could be considered for the treatment or prevention of preterm birth.

【 授权许可】

CC BY   
© The Author(s). 2016