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

Judit Hajagos-Tóth, Judit Bóta, Eszter Ducza, Reza Samavati, Anna Borsodi, Sándor Benyhe, Róbert Gáspár

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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 α2-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 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. Results: Progesterone 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. Conclusions: The 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.

Original languageEnglish
Article number33
JournalReproductive Biology and Endocrinology
Volume14
Issue number1
DOIs
Publication statusPublished - Jun 14 2016

Keywords

  • Gestation
  • Myometrium
  • Progesterone
  • Rat
  • α-adrenergic receptor subtypes

ASJC Scopus subject areas

  • Reproductive Medicine
  • Endocrinology
  • Obstetrics and Gynaecology
  • Developmental Biology

Fingerprint Dive into the research topics of 'The effects of progesterone on the alpha2-adrenergic receptor subtypes in late-pregnant uterine contractions in vitro'. Together they form a unique fingerprint.

  • Cite this