Differences in expression and activity of 11β-hydroxysteroid dehydrogenase type 1 and 2 in human placentas of term pregnancies according to birth weight and gender

Abstract

Background: Fetal exposure to maternal glucocorticoids may determine fetal growth and the programing of later disorders. Availability of the glucocorticoids in the placenta is regulated by the 11b-hydroxysteroid dehydrogenase (11b-HSDs) enzymes. To date, there are discrepancies with regard to cortisol (F) cord blood levels in fetuses with intrauterine growth retardation in different species. Objective: To study the expression and activity of 11b-HSDs in placentas from full term small for gestational age (SGA), appropriate for gestational age (AGA) and large for gestational age (LGA) newborns, and cortisol cord blood concentration. Methods: Twenty-five placentas from AGA, 24 SGA and 25 LGA were collected. Results: SGA newborns had significantly lower and LGA newborns had significantly higher birth weight, birth length, head circumference, and placental weight than AGA counterparts. We observed a direct correlation between placental weight and birth weight, birth length and head circumference, and higher cord F levels in SGA newborns. The 11b-HSD1 expression was similar among the SGA, AGA, and LGA placentas. However, within the placentas of SGA newborns, the 11b-HSD1 mRNA levels were significantly reduced in the chorionic plate compared with basal plate. An inverse correlation between cord F levels and activity of 11b-HSD1 in the chorionic plate of the SGA placentas was detected. The 11b-HSD2 activity was seven-to eightfold higher compared with 11b-HSD1 in the placentas, and there was a lower 11b-HSD2 activity in females' SGA placentas compared with the male SGA placentas. Conclusion: We observed a lower expression and activity of 11b-HSD1 in the chorionic plate of the SGA placentas, suggesting a possible compensatory mechanism to diminish the higher cortisol fetal concentrations observed in fetuses with intrauterine growth restriction.

A gene variant of 11β-hydroxysteroid dehydrogenase type 1 is associated with obesity in children

“…2 --4 Decreased cortisol levels in the liver secondary to reduced 11b-HSD1 expression and activity have been identified; 5 --7 in contrast, increased 11b-HSD1 mRNA levels and enzyme activity have been observed in adult adipose tissue 8 --10 and in children. 11 Controversy exists regarding whether there is a comparable increase in 11b-HSD1 mRNA levels in subcutaneous and omental fat. 3 The mechanism of this dysregulation in human obesity remains uncertain; however, studies in animals have demonstrated a role for 11b-HSD1 in obesity.…”

The effects of intrauterine growth restriction and antenatal glucocorticoids on ovine fetal lung development

“…It is, therefore, possible that higher levels of endogenous glucocorticoids in the IUGR fetus as compared with the appropriately grown fetus (13) may underlie some of these structural and functional lung changes observed in association with IUGR. This is significant because clinically the IUGR fetus has an increased risk of being born preterm (7) and is likely to be treated with antenatal glucocorticoids.…”

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

“…There was a sex-specific correlation between HSD11B2 methylation levels and expression, with females displaying a much stronger correlation between the two factors with no correlation for males. While sex differences in the overall response to prenatal stress has been well described [36], it has not been widely reported in studies focusing on HSD11B2 expression or methylation, although Mericq et al [7] did describe sex as a mediating factor in gene expression. Many of the previous studies focusing on this gene and birth weight have utilized smaller sample sizes, however [9,17], likely leaving them underpowered to determine sex-specific differences in comparison to our analysis of DNA methylation and gene expression from 72 infants.…”

“…HSD11B1 may both convert inactive cortisone to cortisol, or cortisol back to cortisone, and is the major regulator of circulating excess glucocorticoids [6], while HSD11B2 only inactivates glucocorticoids. Placental activity and expression levels of both HSD11B1 [7,8] and HSD11B2 [9,10] have been positively correlated with birth weight, suggesting a link between fetal glucocorticoid metabolism and size at birth.…”