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Antenatal betamethasone depresses maternal and fetal aldosterone levels.

ABSTRACT: Antenatal glucocorticoids are used to mature lung function in fetuses at risk for preterm delivery, but they also suppress cortisol synthesis in both pregnant women and their fetuses. We recently discovered in pregnant rabbits that even though exogenous betamethasone is not a mineralocorticoid, it also suppresses production of aldosterone. Lower aldosterone levels were linked to reduced P450 side chain cleavage(P450scc) messenger RNA levels in the rabbit maternal and fetal adrenal cortex. To establish whether this occurs in humans, we assayed aldosterone levels in women and newborns treated with antenatal betamethasone for preterm labor. In mothers treated with betamethasone, maternal cortisol depression after 48 hours was accompanied by aldosterone depression. Both pregnant women and their newborns treated with betamethasone showed depressed aldosterone levels in a 1- to 3-day period after the first betamethasone dose. We conclude that suppression of aldosterone biosynthesis is a side effect of antenatal steroids that has been largely overlooked, but may be clinically relevant at a time when the newborn is learning to control plasma electrolytes and blood volume.

SUBMITTER: Kessel JM

PROVIDER: S-EPMC3883983 | biostudies-literature | 2009 Jan

REPOSITORIES: biostudies-literature

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Antenatal betamethasone depresses maternal and fetal aldosterone levels.

Kessel Julie M JM Cale Jackie M JM Verbrick Erin E Parker C Richard CR Carlton David P DP Bird Ian M IM

Reproductive sciences (Thousand Oaks, Calif.) 20090101 1

Antenatal glucocorticoids are used to mature lung function in fetuses at risk for preterm delivery, but they also suppress cortisol synthesis in both pregnant women and their fetuses. We recently discovered in pregnant rabbits that even though exogenous betamethasone is not a mineralocorticoid, it also suppresses production of aldosterone. Lower aldosterone levels were linked to reduced P450 side chain cleavage(P450scc) messenger RNA levels in the rabbit maternal and fetal adrenal cortex. To est ...[more]

PMID: 18997118

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Project description:In humans and other species, Longlong-term hypoxia (LTH) during pregnancy can lead to intrauterine growth restriction with reduced body/brain weight, dysregulation of cerebral blood flow (CBF), and other problems in humans and rodents. In contrast, sheep appear to undergo relatively successful acclimatization, not demonstrating any of the above-mentioned problems except at extremely high altitude. To identify the signal transduction genetic pathways and those critical molecules, which may be involved in acclimatization to high altitude LTH, we conducted microarray with advanced bioinformatic analysis on carotid arteries (CA) from the normoxic near-term ovine fetus at sea-level and those acclimatized to high altitude for 110+ days during gestation. In response to LTH acclimatization, in fetal CA we identified, mRNA from 38 genes upregulated (> 2 fFold; (P < 0.05) and 9 genes downregulated (> 2-f Fold; (P < 0.05). The major genes with upregulated mRNA were SLC1A3, Insulin-like growth factor (IGF) binding protein 3, IGF type 2 receptor, transforming growth factor (TGF) Beta-3, and genes involved in the AKT and BCL2 signal transduction networks. The majority of genes with upregulated mRNA have a common motif for Pbx/Knotted homeobox in the promoter region, and Sox family binding sites in the 3M-bM-^@M-^Y un -translated region (UTR). Genes with downregulated mRNA included those involved in the P53 pathway and 5-lipoxygenase activating proteins. The promoter region of all genes with downregulated mRNA, had a common 49 bp region, with a binding site for DOT6 and TOD6, components of the RPD3 histone deacetylase complex RPD3C(L). We also identified miRNA complementary to a number of the altered genes. Thus, the present study identified molecules in the ovine fetus, which may help it to play a role in the acclimatizatione successfully response to high-altitude associated LTH. In these series of experiments we examined changes in gene expression in sheep carotids. Pregnant sheep and non-pregnant adult sheep were exposed to 110 days of hypoxia at 3801 meters of altitude. Carotid arteries from fetuses from non-pregnant adult from sea-level controls and those from high-altitude were compared by Agilent ovine custom array

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Antenatal betamethasone depresses maternal and fetal aldosterone levels.

Publications

Antenatal betamethasone depresses maternal and fetal aldosterone levels.

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