Non-genomic uterorelaxant actions of corticosteroid hormones in rats: An in vitro and in vivo study

We aimed to identify the short-term effects of a glucocorticoid (GC) and a mineralocorticoid (MC) on non-pregnant and late pregnant rat uterine contractions to estimate their tocolytic potential. The in vitro contractility studies were performed with uterine tissues from non-pregnant and 22-day preg...

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Veröffentlicht in:European journal of pharmacology 2022-11, Vol.935, p.175346-175346, Article 175346
Hauptverfasser: Mirdamadi, Mohsen, Schaffer, Annamaria, Barna, Tamara, Samavati, Reza, Szűcs, Kálmán F., Szűcs, Edina, Benyhe, Sándor, Szécsi, Mihály, Gáspár, Róbert
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Sprache:eng
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Zusammenfassung:We aimed to identify the short-term effects of a glucocorticoid (GC) and a mineralocorticoid (MC) on non-pregnant and late pregnant rat uterine contractions to estimate their tocolytic potential. The in vitro contractility studies were performed with uterine tissues from non-pregnant and 22-day pregnant SPRD rats. The cumulative dose-response of fludrocortisone (FLU) and dexamethasone (DEX) was measured alone or in the presence of steroid receptor antagonist mifepristone (MIF) or spironolactone (SPR). [35S]GTPγS and cAMP immunoassays were carried out to detect the activated G-proteins and cAMP, respectively. The in vivo uterine action of single doses of FLU and DEX was measured by smooth muscle electromyography. The results were statistically analyzed with an unpaired t-test. FLU and DEX relaxed both pregnant (33 and 34%) and non-pregnant (37 and 34%) uteri in vitro. MIF inhibited the relaxing effect of DEX, especially in the pregnant uterus, but reduced the effect of FLD only in non-pregnant tissues. GTPγS studies showed a MIF-sensitive elevation in activated G-proteins both in pregnant and non-pregnant uteri by DEX, whereas FLU induced activation only in non-pregnant samples. DEX relaxed pregnant and non-pregnant uteri in vivo in a MIF-sensitive way. DEX can inhibit contractions in the late pregnant uterus in a non-genomic manner, while FLU seems to be ineffective. Its action is mediated by a G-protein-coupled receptor that can be blocked by mifepristone. Further investigations are necessary to determine the required dose and duration of GCs in the therapy of premature birth.
ISSN:0014-2999
1879-0712
DOI:10.1016/j.ejphar.2022.175346