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Paracrine Oxytocin and Estradiol Demonstrate a Spatial Increase in Human Intrauterine Tissues with Labor

Biomedical Research Institute, Biological Sciences and Leicester Warwick Medical School (S.T.), University of Warwick, Coventry, United Kingdom CV4 7AL; and Receptor Screening and Enzyme Technologies, Glaxo-Smithkline (M.J.A.), Stevenage, Hertfordshire, United Kingdom SG1 2NY

Address all correspondence and requests for reprints to: Dr. Steven Thornton, Biomedical Research Institute, Biological Sciences, University of Warwick, Coventry, United Kingdom CV4 7AL. E-mail: sthornton{at}bio.warwick.ac.uk.

In this study we investigated the spatial and temporal relationship among oxytocin (OT), oxytocin receptor (OTR), and estradiol (E2) at term, with (LAB) and without labor (NIL), in human amnion (AM), chorio-decidua (CD), fundal (FU), and lower segment (LS) myometrium. RT-PCR and RIA demonstrated a labor-associated increase in OT mRNA and peptide in CD, AM, and FU, but not LS. HPLC purification and mass spectrometry analysis confirmed that immunoreactive OT corresponded to -amidated OT. Immunohistochemistry localized OT to chorionic trophoblast, decidual stroma, and glandular epithelium. RT-PCR analysis of OTR mRNA demonstrated a significant difference between FU and LS samples, which remained unchanged with labor in all tissues. Immunohistochemistry localized OTR to amniotic epithelium, decidual stroma, and myometrium. Tissue E2 concentrations, as determined by ELISA, demonstrated a significant increase with labor in all tissues. E2 was highest in CD, followed by FU, AM, and LS, respectively. E2 correlated with OT in samples of FU and CD taken from NIL women and in FU, CD, and AM taken from LAB women.

We conclude that a significant increase in both OT and E2 occurs at the myometrial decidual interface with labor, and this increase is reflected in both the fundal and lower segments of the uterus. In contrast to OT and E2 the OTR is spatially regulated, with significantly greater expression in the fundal region of the uterus. Paracrine OT production stimulated by E2 may be important in activating the uterus at term.

This work was supported by GlaxoSmithKline and Wellbeing Grants 434 (to A.B.) and 193 (to N.C.J.d.W.).

Abbreviations: AM, Amnion; CD, chorio-decidua; E2, estradiol; ER, estrogen receptor; FU, fundus; Ig, immunoglobulin; LAB, with labor; LS, lower segment of myometrium; NIL, without labor; OT, oxytocin; OTR, oxytocin receptor.

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