11β-hydroxysteroid dehydrogenase type 1 and pregnancy: Role in the timing of labour onset and in myometrial contraction

Francesco Damiani, Sofia Makieva, Sara F Rinaldi, Lei Hua, Paola Marcolongo, Felice Petraglia, Jane E Norman

Research output: Contribution to journalArticle (Academic Journal)

Abstract

Glucocorticoids play a primary role in the maturation of fetal organs and may contribute to the onset of labour. Glucocorticoid activity depends on the 11β-hydroxysteroid dehydrogenase family (11β-HSDs), catalysing the interconversion between "active" cortisol into inactive cortisone. No definitive study exists on 11β-HSD expression profile in human decidua and myometrium during pregnancy. We investigated the implications of 11β-HSD1 in the regulation of uterine activity in pregnancy, examining its role on contraction of a myocyte cell line and murine 11β-hsd1 levels in utero. Murine 11β-hsd1 mRNA and protein levels in utero progressively increased until the last day of gestation and significantly decreased at the onset of labour (P < 0.0001) (n = 3 to 5 in the various gestational days analysed). Experiments on human myometrial samples confirm the significant fall in 11β-hsd1 mRNA levels at labour, compared to end pregnancy samples (n = 5 to 8). In vitro experiments showed that human myometrial contraction is inhibited by using a non-selective inhibitor of 11β-HSD1. The present study shows the temporal localisation of 11β-HSD1 in uterus, highlighting its importance in the timing of gestation and suggesting its contribution in the myometrium contraction.

Original languageEnglish
Pages (from-to)79-86
Number of pages8
JournalMolecular and Cellular Endocrinology
Volume447
DOIs
Publication statusPublished - 15 May 2017

Bibliographical note

Copyright © 2017 Elsevier B.V. All rights reserved.

Keywords

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1/genetics
  • 11-beta-Hydroxysteroid Dehydrogenase Type 2/genetics
  • Animals
  • Carbenoxolone/pharmacology
  • Cell Line
  • Female
  • Humans
  • Labor, Obstetric
  • Mice, Inbred C57BL
  • Myometrium/drug effects
  • Pregnancy
  • Time Factors
  • Uterine Contraction/drug effects

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