title: 11β-hydroxysteroid dehydrogenase type 1 and pregnancy: Role in the timing of labour onset and in myometrial contraction.
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.
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy. Electronic address: francesco.damiani@yahoo.com.
authors.forename: Francesco
authors.initials: F
authors.lastname: Damiani
authors.affiliation: Tommy's Centre for Maternal and Fetal Health at the Medical Research Council Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom.
authors.forename: Sofia
authors.initials: S
authors.lastname: Makieva
authors.affiliation: Tommy's Centre for Maternal and Fetal Health at the Medical Research Council Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom.
authors.forename: Sara F
authors.initials: SF
authors.lastname: Rinaldi
authors.affiliation: Tommy's Centre for Maternal and Fetal Health at the Medical Research Council Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom.
authors.forename: Lei
authors.initials: L
authors.lastname: Hua
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Marcolongo
authors.affiliation: Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: Petraglia
authors.affiliation: Tommy's Centre for Maternal and Fetal Health at the Medical Research Council Centre for Reproductive Health, University of Edinburgh, Queen's Medical Research Institute, Edinburgh, United Kingdom.
authors.forename: Jane E
authors.initials: JE
authors.lastname: Norman
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000235:genetics / Q000378:metabolism*; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D002460:Cell Line; D005260:Female; D006801:Humans; D007743:Labor, Obstetric; D008810:Mice, Inbred C57BL; D009215:Myometrium / Q000187:drug effects / Q000502:physiology*; D011247:Pregnancy; D013997:Time Factors; D014590:Uterine Contraction / Q000187:drug effects / Q000502:physiology*
chemical_list: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D002229:Carbenoxolone
keywords: 11beta-HSD; Cortisol; Labour; Myometrium; Pregnancy