11β–Hydroxysteroid Dehydrogenase Type 1 Activity in Short Small-For-GA Children and in Response to GH Therapy

Zuckerman‐Levin, Nehama; Tsivlin, Larisa; Knopf, Carlos; Flor, O.; Shen‐Orr, Zila; Levin, Moshe; Hochberg, Zèev

doi:10.1203/pdr.0b013e3182226a0c

Cited by 6 publications

(3 citation statements)

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“…The overexpression of isoform HSD11B1 in >37 weeks gestation neonates is in line with published observations [26]. It is tempting to speculate whether enzymatic activities of the HSD11 isoforms are changed in a gestational age dependent manner, as this has been demonstrated in children born small for gestational age with lack of catch-up growth who were found to have lower activity of HSD11B1 [77].…”

Section: Discussionsupporting

confidence: 87%

Transcriptome Changes Affecting Hedgehog and Cytokine Signalling in the Umbilical Cord: Implications for Disease Risk

et al. 2012

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BackgroundBabies born at lower gestational ages or smaller birthweights have a greater risk of poorer health in later life. Both the causes of these sub-optimal birth outcomes and the mechanism by which the effects are transmitted over decades are the subject of extensive study. We investigated whether a transcriptomic signature of either birthweight or gestational age could be detected in umbilical cord RNA.MethodsThe gene expression patterns of 32 umbilical cords from Singaporean babies of Chinese ethnicity across a range of birthweights (1698–4151 g) and gestational ages (35–41 weeks) were determined. We confirmed the differential expression pattern by gestational age for 12 genes in a series of 127 umbilical cords of Chinese, Malay and Indian ethnicity.ResultsWe found that the transcriptome is substantially influenced by gestational age; but less so by birthweight. We show that some of the expression changes dependent on gestational age are enriched in signal transduction pathways, such as Hedgehog and in genes with roles in cytokine signalling and angiogenesis. We show that some of the gene expression changes we report are reflected in the epigenome.ConclusionsWe studied the umbilical cord which is peripheral to disease susceptible tissues. The results suggest that soma-wide transcriptome changes, preserved at the epigenetic level, may be a mechanism whereby birth outcomes are linked to the risk of adult metabolic and arthritic disease and suggest that greater attention be given to the association between premature birth and later disease risk.

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Section: Discussionsupporting

confidence: 87%

Transcriptome Changes Affecting Hedgehog and Cytokine Signalling in the Umbilical Cord: Implications for Disease Risk

et al. 2012

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“…In a study involving prepubertal children with short stature, a 4-wk challenge with GH caused reproducible changes in body fluid handling: there was a decrease in fractional excretion of water and increase in serum aldosterone (46), an intriguing observation given the relationship between secondary aldosteronism and pediatric PTCS (see above). Another study illustrated that GH therapy suppressed basal and glucocorticoid-stimulated HSD1 activity which may directly induce a relative cortisol deficiency (47). …”

Section: Association Of Ptcs and Endocrinopathiesmentioning

confidence: 99%

An integrated mechanism of pediatric pseudotumor cerebri syndrome: evidence of bioenergetic and hormonal regulation of cerebrospinal fluid dynamics

et al. 2014

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Pseudotumor cerebri syndrome (PTCS) is defined by the presence of elevated intracranial pressure (ICP) in the setting of normal brain parenchyma and cerebrospinal fluid (CSF). Headache, vision changes, and papilledema are common presenting features. Up to 10% of appropriately treated patients may experience permanent visual loss. The mechanism(s) underlying PTCS is unknown. PTCS occurs in association with a variety of conditions, including kidney disease, obesity, and adrenal insufficiency, suggesting endocrine and/or metabolic derangements may occur. Recent studies suggest that fluid and electrolyte balance in renal epithelia is regulated by a complex interaction of metabolic and hormonal factors; these cells share many of the same features as the choroid plexus cells in the central nervous system (CNS) responsible for regulation of CSF dynamics. Thus, we posit that similar factors may influence CSF dynamics in both types of fluid-sensitive tissues. Specifically, we hypothesize that, in patients with PTCS, mitochondrial metabolites (glutamate, succinate) and steroid hormones (cortisol, aldosterone) regulate CSF production and/or absorption. In this integrated mechanism review, we consider the clinical and molecular evidence for each metabolite and hormone in turn. We illustrate how related intracellular signaling cascades may converge in the choroid plexus, drawing on evidence from functionally similar tissues.

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“…In addition, placental HSD11B2 expression and activity has been associated with infant birth weight and fetal growth [22], as well as preeclampsia [16,17]. Lowered placental HSD11B1 activity at birth has also been linked to reduced childhood growth of small for gestational age (SGA) infants at 7 yr of age, implicating it in postnatal growth [23]. There are, however, no published data comprehensively investigating DNA methylation, expression, and the interplay between the two HSD11B isoforms on birth weight.…”

Section: Introductionmentioning

confidence: 99%

The Role of Placental 11-Beta Hydroxysteroid Dehydrogenase Type 1 and Type 2 Methylation on Gene Expression and Infant Birth Weight1

Green

Armstrong

Lesseur

et al. 2015

Biology of Reproduction

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Maternal stress has been linked to infant birth weight outcomes, which itself may be associated with health later in life. The placenta acts as a master regulator for the fetal environment, mediating intrauterine exposures to stress through the activity of genes regulating glucocorticoids, including the 11beta-hydroxysteroid dehydrogenase (HSD11B) type 1 and 2 genes, and so we hypothesized that variation in these genes will be associated with infant birth weight. We investigated DNA methylation levels at six sites across the two genes, as well as mRNA expression for each, and the relationship to infant birth weight. Logistic regressions correcting for potential confounding factors revealed a significant association between methylation at a single CpG site within HSD11B1 and being born large for gestational age. In addition, our analysis identified correlations between methylation and gene expression, including sex-specific transcriptional regulation of HSD11B2. Our work is one of the first comprehensive views of DNA methylation and expression in the placenta for both HSD11B types 1 and 2, linking epigenetic alterations with the regulation of fetal stress and birth weight outcomes.

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11β–Hydroxysteroid Dehydrogenase Type 1 Activity in Short Small-For-GA Children and in Response to GH Therapy

Cited by 6 publications

References 55 publications

Transcriptome Changes Affecting Hedgehog and Cytokine Signalling in the Umbilical Cord: Implications for Disease Risk

Transcriptome Changes Affecting Hedgehog and Cytokine Signalling in the Umbilical Cord: Implications for Disease Risk

An integrated mechanism of pediatric pseudotumor cerebri syndrome: evidence of bioenergetic and hormonal regulation of cerebrospinal fluid dynamics

The Role of Placental 11-Beta Hydroxysteroid Dehydrogenase Type 1 and Type 2 Methylation on Gene Expression and Infant Birth Weight1

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