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

• Published in: Life sciences (1973) Vol. 263; p. 118584
• Main Authors: Mirdamadi, Mohsen, Kothencz, Anna, Szűcs, Edina, Benyhe, Sándor, Szécsi, Mihály, Gáspár, Róbert
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 15-12-2020; Elsevier BV
• Subjects: 17β-Estradiol; Actinomycin; Animals; Contractility; Cyclic AMP; Cycloheximide; Dose-Response Relationship, Drug; Endometrium; Endothelium; Estradiol - administration & dosage; Estradiol - pharmacology; Female; Flutamide; Flutamide - pharmacology; Fulvestrant; Fulvestrant - pharmacology; G protein-coupled receptors; Genomics; Hormones; In vitro methods and tests; Mifepristone; Mifepristone - pharmacology; Muscle Contraction - drug effects; Myometrial contraction; Non-genomic pathway; Potassium chloride; Potassium Chloride - pharmacology; Pregnancy; Progesterone; Progesterone - administration & dosage; Progesterone - pharmacology; Proteins; Rat; Rats; Rats, Sprague-Dawley; Receptors; Sex; Sex hormones; Steroid hormones; Steroids; Testosterone; Testosterone - administration & dosage; Testosterone - pharmacology; Uterine Contraction - drug effects; Uterus; Pregnancy; Sex hormones; Mifepristone; Myometrial contraction; Rat; Non-genomic pathway
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2020.118584

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.
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.
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.
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.