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Τετάρτη 29 Νοεμβρίου 2017

Comparative Profiling of Adrenal Steroids in Maternal and Umbilical Cord Blood

Publication date: Available online 28 November 2017
Source:The Journal of Steroid Biochemistry and Molecular Biology
Author(s): Simon Travers, Laetitia Martinerie, Pascal Boileau, Qiong-Yao Xue, Marc Lombès, Eric Pussard
Fetal steroidome in late pregnancy receives multiple contributions from both maternal and fetal adrenals as well as from placenta. Depressed glucocorticoid levels have been reported in fetal blood at birth, yet studies on mineralocorticoid pathways are sparse. To investigate biosynthesis pathways at birth, adrenal steroids profiles were established in paired mothers and neonates. Forty-six paired healthy term newborns and their mothers from the Aldo cohort were assessed. Steroidomic profiles of mineralocorticoids, glucocorticoids and adrenal androgens were established from umbilical cord and maternal blood at birth using a highly sensitive and specific LC-MS/MS methodology. As compared to maternal blood, umbilical cord blood exhibited high levels of steroids precursors (progesterone and 11-deoxycorticosterone) contrasting with a collapse in corticosterone levels. Consecutively, 18-hydroxycorticosterone and aldosterone levels were also depressed in neonates. Similarly, umbilical cord blood levels of both 17-hydroxyprogesterone and 11-deoxycortisol were higher while cortisol levels sharply decreased. The product-to-substrate ratios evaluating the 11-hydroxylation step (corticosterone/11-deoxycorticosterone and cortisol/11-deoxycortisol) fell for both pathways. As expected, cortisone and 11-dehydrocorticosterone levels exceed those of cortisol and corticosterone in umbilical cord blood reflecting the strong placental 11-β-hydroxysteroid-dehydrogenase type 2 (11βHSD2) activity. Dehydroepiandrosterone-sulphate levels are higher in neonates, while both androstenedione and testosterone levels sharply fell. No significant difference in steroid levels could be observed according the gender except higher testosterone concentrations in umbilical cord of boys. Moreover, a strong and negative relationship between testosterone and progesterone levels was recorded in umbilical cord of boys. These adrenal steroidomic profiling demonstrate a deficit in mineralocorticoids (aldosterone, 18-hydroxycorticosterone and corticosterone) and glucocorticoids (cortisol) in term neonates, reflecting either a relative defect in 11-hydroxylase activity or more likely the strong placental 11-β-HSD2 activity. Collectively, these findings should be taken into account for a better understanding of regulatory interactions between placenta and fetal adrenal.



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