Effects of thyrotropin-releasing hormone on human myometrium and umbilical vasculature in vitro S. M. Potter, MB BCh, K. Astbury, MRCOG, J. J. Morrison, MD, MRCOG, FRCPI* Department of Obstetrics and Gynaecology, National University of Ireland Galway, Clinical Science Institute, University College Hospital, Galway, Ireland Received January 31, 2003; revised June 5, 2003; accepted June 26, 2003 – Objective: The purpose of this study was to investigate the direct effects of thyrotropin-releasing hormone on isolated human myometrium that was obtained during pregnancy and on human umbilical vasculature in vitro. Study design: Isolated human myometrial strips were dissected from biopsy specimens that were obtained at elective cesarean delivery and suspended for isometric recording under physiologic conditions. The effects of cumulative additions of thyrotropin-releasing hormone (10 ÿ9 -10 ÿ4 mol/L) on oxytocin-induced myometrial contractility were evaluated. The effects of thyrotro- pin-releasing hormone (10 ÿ9 -10 ÿ4 mol/L) on umbilical vessel (artery and vein) resistance in vitro were investigated with the use of isolated ring preparations. Results: Thyrotropin-releasing hormone exerted a significant concentration-dependent relaxant effect on pregnant human myometrial tissue, which ranged from 3.54% (10 ÿ9 mol/L, P = .935) to a net cumulative total of 21.06% (10 ÿ4 mol/L, P!.001). Thyrotropin-releasing hormone also exerted a concentration-dependent relaxant effect on human umbilical vasculature that ranged from 12.51% (10 ÿ9 mol/L, P = .994) to a net cumulative total of 23.27%G4.87% (SEM, 10 ÿ4 mol/L, P!.01) in umbilical artery. For umbilical vein, the relaxant effect ranged from 1.80% (10 ÿ9 mol/L, P = .998) to a net cumulative total of 14.64% (10 ÿ4 mol/L, P!.009). Conclusion: Thyrotropin-releasing hormone exerts a significant relaxant effect in human myome- trium and in human umbilical vasculature and highlights a potential physiologic role for this neu- ropeptide in these tissues. These findings have clinical implications for the therapeutic use of thyrotropin-releasing hormone antenatally. Ó 2004 Elsevier Inc. All rights reserved. KEY WORDS Thyrotropin-releasing hormone Human myometrium Umbilical artery Umbilical vein – Thyrotropin-releasing hormone (TRH; (Sigma- Aldrich, Dublin, Ireland) has been investigated exten- sively for its role in the prevention of respiratory distress syndrome by administration antenatally. Although it is not recommended currently for widespread clinical use, 1,2 TRH is believed to still have a role, in conjunc- tion with corticosteroids, in situations in which surfac- tant is not available. 3 Although it is known that TRH exerts a significant modulatory effect on nonvascular 4,5 and vascular smooth muscle, 6,7 little is known about the potential direct effects of TRH on human uterine * Reprint requests: John J. Morrison, MD, FRCOG, FRCPI, National University of Ireland Galway, Department of Obstetrics and Gynecology, Clinical Science Institute, Newcastle Road, Galway, Ireland. E-mail: john.morrison@nuigalway.ie www.elsevier.com/locate/ajog American Journal of Obstetrics and Gynecology (2004) 190, 246e51 0002-9378/$ - see front matter Ó 2004 Elsevier Inc. All rights reserved. doi:10.1016/S0002-9378(03)00853-6