Influence of labor on direct and indirect determinants of placental 11beta-hydroxysteroid dehydrogenase activity
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MATERNAL-FETAL MEDICINE
Influence of labor on direct and indirect determinants of placental 11beta‑hydroxysteroid dehydrogenase activity Hanna Huebner1 · Kirsten Heussner2 · Matthias Ruebner1 · Matthias Schmid3 · Jennifer Nadal3 · Joachim Woelfle2 · Andrea Hartner2 · Carlos Menendez‑Castro2 · Manfred Rauh2 · Matthias W. Beckmann1 · Sven Kehl1 · Fabian B. Fahlbusch2 Received: 1 May 2020 / Accepted: 21 August 2020 © The Author(s) 2020
Abstract Purpose Labor is a complex process involving multiple para-, auto- and endocrine cascades. The interaction of cortisol, corticotropin-releasing hormone (CRH) and progesterone is essential. The action of cortisol on the human feto-placental unit is regulated by 11beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2/HSD11B2) that converts cortisol into inactive cortisone. The majority of studies on the assessment of placental 11β-HSD2 function determined indirect activity parameters. It remains elusive if indirect measurements correlate with enzymatic function and if these parameters are affected by potential confounders (e.g., mode of delivery). Thus, we compared determinants of indirect 11β-HSD2 tissue activity with its direct enzymatic turnover rate in placental samples from spontaneous births and cesarean (C)-sections. Methods Using LC–MS/MS, we determined CRH, cortisol, cortisone, progesterone and 17-hydroxy(OH)-progesterone in human term placentas (spontaneous birth vs. C-section, n = 5 each) and measured the enzymatic glucocorticoid conversion rates in placental microsomes. Expression of HSD11B1, 2 and CRH was determined via qRT-PCR in the same samples. Results Cortisol–cortisone ratio correlated with direct microsomal enzymatic turnover. While this observation seemed independent of sampling site, a strong influence of mode of delivery on tissue steroids was observed. The mRNA expression of HSD11B2 correlated with indirect and direct cortisol turnover rates in C-section placentas only. In contrast to C-sections, CRH, cortisol and cortisone levels were significantly increased in placental samples following spontaneous birth. Conclusion Labor involves a series of complex hormonal processes including activation of placental CRH and glucocorticoid metabolism. This has to be taken into account when selecting human cohorts for comparative analysis of placental steroids. Keywords LC–MS/MS · Placenta · Mode of delivery · CRH · 11beta-hydroxysteroid dehydrogenase
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00404-020-05755-4) contains supplementary material, which is available to authorized users. * Fabian B. Fahlbusch fabian.fahlbusch@uk‑erlangen.de 1
Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center ErlangenEMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany
2
Department of Pediatrics and Adolescent Medicine, Friedrich-Alexander-University of Erlangen-Nuremberg, Loschgestr. 15, 91054 Erlangen, Germany
3
Institute of Medical Bi
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