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Intracrine Control of Estrogen Action in Human Gestational Tissues at Parturition

Tamas Zakar, MD, PhD

Ursula Manuelpillai, PhD

Euan Wallace, MD

Kenneth Kwek, MD

George S. H. Yeo, MD

Roger Smith, MD, PhD

Mothers and Babies Research Centre, University of Newcastle and John Hunter Hospital, Newcastle, New South Wales, Australia; Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia; Department of Maternal Fetal Medicine, KK Women's and Children's Hospital, Singapore, Singapore

Sam Mesiano, PhD

Mothers and Babies Research Centre, University of Newcastle and John Hunter Hospital, Newcastle, New South Wales, Australia; Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia; Department of Maternal Fetal Medicine, KK Women's and Children's Hospital, Singapore, Singapore smesiano{at}mail.newcastle.edu.au

Objective: We examined whether estrogen action in human parturition is regulated by an intracrine mechanism mediated by target tissue expression of specific 17ß-hydroxysteroid dehydrogenase (17ßHSD) isozymes that interconvert estrone (E1) and estradiol (E2), such that the onset of labor is associated with an increase in local E2 bioavailability.

Methods: The extent of 17ßHSD-1, -2, -3, -4, -5, and -7 expression (measured by quantitative reverse transcripts polymerase chain reaction) and the capacity to interconvert E1 and E2 were compared in amnion, chorion, placenta, decidua, and myometrium obtained from women at term before (n = 6) and after (n = 6) the onset of labor.

Results: In chorion, abundance of 17ßHSD-1 (converts E1 to E2) mRNA decreased 2.7-fold (P < .05) in association with labor onset. In myometrium, 17ßHSD-1 and 17ßHSD-4 (con converts E2 to E1) mRNAs increased two-fold and five-fold, respectively, with the onset of labor (P < .05 for each). No other statistically significant labor-associated change in 17ßHSD expression was observed. In chorion, 17ßHSD oxidative (E2 to E1) and reductive (E1 to E2) activities and the net E2 synthetic capacity increased with labor. In decidua, both activities decreased with the onset of labor, but there was no change in net E2 synthetic capacity. The capacity to interconvert E1 and E2 did not change in the other tissues.

Conclusion: The increase in E2 synthetic capacity in the chorion might contribute to an increase in local estrogen bioactivity in association with the onset of labor. However, it cannot be explained by changes in 17ßHSD isozyme expression and is unlikely to account for the increased estrogen action at parturition. These data show that intractive mechanisms based on 17ßHSD isozyme expression play a minor role, if any, in controlling estrogen action in gestational tissues during human parturition.

Key Words: Estrogen action • human parturition • intracrine regulation • 17ß-hydroxyteroid dehydrogenase isozymes expression • enzyme activity

Journal of the Society for Gynecologic Investigation, Vol. 11, No. 4, 213-219 (2004)
DOI: 10.1016/j.jsgi.2003.12.003


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