Non-genomic actions of sex hormones on pregnant uterine contractility in rats: An in vitro study at term

Life Sci. 2020 Dec 15:263:118584. doi: 10.1016/j.lfs.2020.118584. Epub 2020 Oct 13.


Aims: The non-genomic (prompt) actions of sex steroids on pregnant uterine contractility are not fully explored yet, the aim of our study was to clarify such effects of 17-β estradiol (E2), progesterone (P4) and testosterone (T) on late (22-day) pregnant uterine contractions together with the signaling pathways in rats in vitro.

Methods: The uterine effects of sex steroids on KCl-stimulated contractions were examined in the presence of genomic pathway blocker actinomycin D and cycloheximide, sex hormone receptor antagonists (flutamide, fulvestrant, mifepristone) and also after removing the endometrium. The modifications in uterine G-protein activation and cAMP levels were also detected.

Results: T and E2 both relaxed the uterine contractions in the concentration range of 10-8-10-3 M with an increase in the activated G-protein and cAMP levels of the uterus, while P4 was ineffective. Cycloheximide, actinomycin D, antagonist for T and E2 were not able to modify the responses along with the endothelium removal. Mifepristone blocked the relaxing effects of T and E2 and reduced the activation of G-protein and the formation of cAMP.

Significance: T and E2 can inhibit KCl-stimulated contractions in the late pregnant uterus in high concentrations and in a non-genomic manner. Their actions are mediated by a G-protein coupled receptor that can be blocked by mifepristone. A single and high dose of T or E2 might be considered in premature contractions, however, further preclinical and clinical studies are required for the approval of such a therapeutic intervention.

Keywords: Mifepristone; Myometrial contraction; Non-genomic pathway; Pregnancy; Rat; Sex hormones.

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Estradiol / administration & dosage
  • Estradiol / pharmacology*
  • Female
  • Flutamide / pharmacology
  • Fulvestrant / pharmacology
  • Mifepristone / pharmacology
  • Muscle Contraction / drug effects
  • Potassium Chloride / pharmacology
  • Pregnancy
  • Progesterone / administration & dosage
  • Progesterone / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Testosterone / administration & dosage
  • Testosterone / pharmacology*
  • Uterine Contraction / drug effects*


  • Fulvestrant
  • Mifepristone
  • Testosterone
  • Progesterone
  • Estradiol
  • Potassium Chloride
  • Flutamide