Oestrogen modulation with parturition in the human placenta

Leslie, Kimberly K.; Schruefer, John J.; Burchell, Mary; Smith, Jacqueline A.; Albertson, Barry D.

doi:10.1016/s0143-4004(05)80238-3

Cited by 11 publications

(6 citation statements)

References 37 publications

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“…Labor is associated with increased fetal and maternal stress leading to elevated adrenal steroid (DHEAS) production. In addition, placental aromatase activity has been reported to decrease with labor [52], in which case placental conversion of androgens to estrogens should be reduced, again tending to result in increased fetal androgen levels. Several researchers have previously described increases in cord blood levels of A4 [21], [23] and DHEA [21], [53] with labor, speculating that this reflects increased production of C19 steroids by the fetal adrenal in association with a labor-induced HPA stress response.…”

Section: Discussionmentioning

confidence: 99%

Androgen Concentrations in Umbilical Cord Blood and Their Association with Maternal, Fetal and Obstetric Factors

et al. 2012

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The aim of this study was to measure umbilical blood androgen concentrations in a birth cohort using a highly specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay and assesses the effects of sex, labor, and gestational age on fetal androgen levels at birth. We performed a prospective cohort study of androgen concentrations in mixed arterial and venous umbilical cord serum from 803 unselected singleton pregnancies from a general obstetric population in Western Australia. Total testosterone (TT), Δ4-androstenedione, and dehydroepiandrosterone were extracted from archived cord serum samples and measured using LC-MS/MS. SHBG was measured by ELISA; free testosterone (FT) and bioavailable testosterone (BioT) values were also calculated. Median values for all three androgens were generally lower than previously published values. Levels of TT, FT, BioT, and SHBG were significantly higher in male verses female neonates (P<0.0001), while dehydroepiandrosterone levels were higher in females (P<0.0001). Labor was associated with a significant (∼15–26%) decrease in median cord blood TT and FT levels (both sexes combined), but a modest (∼16–31%) increase in SHBG, Δ4-androstenedione, and dehydroepiandrosterone concentrations. TT and FT were significantly negatively correlated with gestational age at delivery, while SHBG, Δ4-androstenedione, and dehydroepiandrosterone were positively correlated. Antenatal glucocorticoid administration also had a significant effect in the multiple regression models. This is the first study to report umbilical cord androgen levels in a large unselected population of neonates using LC-MS/MS. Our findings suggest that previous studies have over-estimated cord androgen levels, and that fetal, maternal, and obstetric factors influence cord androgen levels differentially. Caution should be exercised when interpreting previously-published data that have not taken all of these factors into account.

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Section: Discussionmentioning

confidence: 99%

Androgen Concentrations in Umbilical Cord Blood and Their Association with Maternal, Fetal and Obstetric Factors

et al. 2012

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“…STS allows access of DHEA to the HSD3B1 and CYP19A1 within the syncytiotrophoblast layer and conversion to estrogens [120]. Placental STS is independent of substrate concentration [121] and of GA [122][123][124].…”

Section: Steroid Sulfatases and Placental Production Of Sex Hormonesmentioning

confidence: 99%

“…The specific activities of HSD3Bs for C-21 steroids in mitochondrial and microsomal preparations from human term placenta are about two times higher than for the C-19 steroids [128]. Like in the case of sulfatase activity, placental HSD3B1 activities are constant throughout the human gestation [129,122,123] and around parturition [124,130]. Progesterone and DHEAS may cause marked HSD3Bs inhibition in physiological conditions [121,131].…”

Section: ˇ-Hydroxysteroid Dehydrogenase Activitymentioning

confidence: 99%

Steroid metabolome in fetal and maternal body fluids in human late pregnancy

Hill

Pařı́zek

Cibula

et al. 2010

The Journal of Steroid Biochemistry and Molecular Biology

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“…Activity and inhibition of the aromatase, 17β-HSD1 and STS enzymes were assessed with radioincubation methods described in detail in our previous publications [3,16]. These methods are based on adapted literature techniques and used human placental microsoma suspension and cytosol as source of the enzymes (references: for aromatase [48]; for 17β-HSD1 [50]; and for STS [21]. Incubation parameters were optimized in preliminary experiments.…”

Section: Enzyme Experimentsmentioning

confidence: 99%

Steroidal ferrocenes as potential enzyme inhibitors of the estrogen biosynthesis

et al. 2020

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The potential inhibitory effect of diverse triazolyl-ferrocene steroids on key enzymes of the estrogen biosynthesis was investigated. Test compounds were synthesized via copper-catalyzed cycloaddition of steroidal azides and ferrocenyl-alkynes using our efficient methodology published previously. Inhibition of human aromatase, steroid sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) activities was investigated with in vitro radiosubstrate incubations. Some of the test compounds were found to be potent inhibitors of the STS. A compound bearing ferrocenyl side chain on the C-2 displayed a reversible inhibition, whereas C-16 and C-17 derivatives displayed competitive irreversible binding mechanism toward the enzyme. 17α-Triazolyl-ferrocene derivatives of 17β-estradiol exerted outstanding inhibitory effect and experiments demonstrated a key role of the ferrocenyl moiety in the enhanced binding affinity. Submicromolar IC50 and Ki parameters enroll these compounds to the group of the most effective STS inhibitors published so far. STS inhibitory potential of the steroidal ferrocenes may lead to the development of novel compounds able to suppress in situ biosynthesis of 17β-estradiol in target tissues.

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Oestrogen modulation with parturition in the human placenta

Cited by 11 publications

References 37 publications

Androgen Concentrations in Umbilical Cord Blood and Their Association with Maternal, Fetal and Obstetric Factors

Androgen Concentrations in Umbilical Cord Blood and Their Association with Maternal, Fetal and Obstetric Factors

Steroid metabolome in fetal and maternal body fluids in human late pregnancy

Steroidal ferrocenes as potential enzyme inhibitors of the estrogen biosynthesis

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