Non-genomic uterorelaxant actions of corticosteroid hormones in rats : An in vitro and in vivo study
Copyright © 2022. Published by Elsevier B.V..
AIMS: 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.
METHODS: 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.
RESULTS: 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.
SIGNIFICANCE: 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:935 |
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| Enthalten in: |
European journal of pharmacology - 935(2022) vom: 15. Nov., Seite 175346 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mirdamadi, Mohsen [VerfasserIn] |
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| Links: |
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| Themen: |
320T6RNW1F |
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| Anmerkungen: |
Date Completed 08.11.2022 Date Revised 08.11.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ejphar.2022.175346 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM347945104 |
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| 100 | 1 | |a Mirdamadi, Mohsen |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Non-genomic uterorelaxant actions of corticosteroid hormones in rats |b An in vitro and in vivo study |
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| 500 | |a Date Revised 08.11.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2022. Published by Elsevier B.V. | ||
| 520 | |a AIMS: 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 | ||
| 520 | |a METHODS: 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 | ||
| 520 | |a RESULTS: 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 | ||
| 520 | |a SIGNIFICANCE: 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Corticosteroid hormones | |
| 650 | 4 | |a Mifepristone | |
| 650 | 4 | |a Myometrial contraction | |
| 650 | 4 | |a Non-genomic pathway | |
| 650 | 4 | |a Pregnancy | |
| 650 | 4 | |a Rat | |
| 650 | 7 | |a Mifepristone |2 NLM | |
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| 650 | 7 | |a Adrenal Cortex Hormones |2 NLM | |
| 700 | 1 | |a Schaffer, Annamaria |e verfasserin |4 aut | |
| 700 | 1 | |a Barna, Tamara |e verfasserin |4 aut | |
| 700 | 1 | |a Samavati, Reza |e verfasserin |4 aut | |
| 700 | 1 | |a Szűcs, Kálmán F |e verfasserin |4 aut | |
| 700 | 1 | |a Szűcs, Edina |e verfasserin |4 aut | |
| 700 | 1 | |a Benyhe, Sándor |e verfasserin |4 aut | |
| 700 | 1 | |a Szécsi, Mihály |e verfasserin |4 aut | |
| 700 | 1 | |a Gáspár, Róbert |e verfasserin |4 aut | |
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