Intrauterine growth restriction (IUGR) may influence adrenocortical function, lipid metabolism and glucose tolerance in later life. Both cortisol (F) synthesis and metabolism contribute to serum F concentrations, 11β...Intrauterine growth restriction (IUGR) may influence adrenocortical function, lipid metabolism and glucose tolerance in later life. Both cortisol (F) synthesis and metabolism contribute to serum F concentrations, 11β -hydroxysteroid dehydrogenase type 2 (11β -HSD2) enzyme converts F to biologically inactive cortisone (E). Decreased 11β -HSD2 activity has been suggested for a reason to IUGR and to its metabolic consequences. Our aim was to develop a specific liquid chromatography -tandem mass spectrometry (LC-MS/MS) method for analysing serum F and E concentrations, to determine the F/E ratios, and to correlate them with serum lipid concentrations, insulin resistance index (HOMA-IR), and catch-up growth in children born small for gestational age (SGA). The mean serum F and E concentrations, and F/E ratios did not differ between the SGA and their control children at 12 y age. The SGA children in the highest F/E ratio quartile had poorer gain in height between 0-12 y, and higher serum total and LDL cholesterol levels than those with lower F/E ratios. In logistic regression analysis, high LDL cholesterol, high HOMA-IR, and early pubertal stage associated with high F/E ratio in the SGA children. In conclusion, our LC-MS/MS method enables a reliable measurement of both F and E concentrations from a single serum sample. High serum F/E ratio may be associated with IUGR, its metabolic consequences, and poor catch-up growth in a subset of SGA children.展开更多
The placental enzyme 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2) transforms maternal cortisol to inactive cortisone. Fetal glucocorticoid excess due to reduced 11β-HSD2 activity could make small preterm infants s...The placental enzyme 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2) transforms maternal cortisol to inactive cortisone. Fetal glucocorticoid excess due to reduced 11β-HSD2 activity could make small preterm infants susceptible to early adrenal insufficiency when the maternal cortisol source is no longer sustained. We assessed whether placental 11β-HSD2 activity is related to early adrenal insufficiency and postnatal clinical course in extremely low birth weight (<1000 g) infants. Mean gestational age of the 44 infants was 26.6wk (range,23.7-32.0),birth weight was 747 g (440-981),and relative birth weight was -1.9 SD (-4.9 to 1.0). We determined placental 11β-HSD2 activity,baseline,and ACTH-stimulated cortisol and assessed illness severity by the Score of Neonatal Acute Physiology (SNAP). One standard deviation decrease in placental 11β-HSD2 activity corresponded to a 1.85 (95%CI 0.55 to 3.14; p = 0.006) unit increase in SNAP score and 2.9 mm Hg decrease in minimum mean arterial pressure (95%CI 0.3 to 5.6 mm Hg; p=0.03). Placental 11β-HSD2 activity was not associated with cortisol concentrations,although the confidence interval of the ACTH-stimulated cortisol was close to zero:1 SD increase corresponded to 17%(-18%to 49%) increase in ACTH-stimulated cortisol. Moreover,a 1 SD decrease in enzyme activity was associated with a hazard ratio for postnatal glucocorticoid treatment of 1.63 (95%CI 1.00 to 2.65); p = 0.05. In ELBW infants,lower placental 11β-HSD2 activity is associated with more severe early postnatal illness and hypotension. Although an association with baseline or ACTH-stimulated cortisol was not seen,possible relationships with other components of the hypothalamic-pituitary-adrenal axis remain to be determined.展开更多
文摘Intrauterine growth restriction (IUGR) may influence adrenocortical function, lipid metabolism and glucose tolerance in later life. Both cortisol (F) synthesis and metabolism contribute to serum F concentrations, 11β -hydroxysteroid dehydrogenase type 2 (11β -HSD2) enzyme converts F to biologically inactive cortisone (E). Decreased 11β -HSD2 activity has been suggested for a reason to IUGR and to its metabolic consequences. Our aim was to develop a specific liquid chromatography -tandem mass spectrometry (LC-MS/MS) method for analysing serum F and E concentrations, to determine the F/E ratios, and to correlate them with serum lipid concentrations, insulin resistance index (HOMA-IR), and catch-up growth in children born small for gestational age (SGA). The mean serum F and E concentrations, and F/E ratios did not differ between the SGA and their control children at 12 y age. The SGA children in the highest F/E ratio quartile had poorer gain in height between 0-12 y, and higher serum total and LDL cholesterol levels than those with lower F/E ratios. In logistic regression analysis, high LDL cholesterol, high HOMA-IR, and early pubertal stage associated with high F/E ratio in the SGA children. In conclusion, our LC-MS/MS method enables a reliable measurement of both F and E concentrations from a single serum sample. High serum F/E ratio may be associated with IUGR, its metabolic consequences, and poor catch-up growth in a subset of SGA children.
文摘The placental enzyme 11β-hydroxysteroid dehydrogenase-2 (11β-HSD2) transforms maternal cortisol to inactive cortisone. Fetal glucocorticoid excess due to reduced 11β-HSD2 activity could make small preterm infants susceptible to early adrenal insufficiency when the maternal cortisol source is no longer sustained. We assessed whether placental 11β-HSD2 activity is related to early adrenal insufficiency and postnatal clinical course in extremely low birth weight (<1000 g) infants. Mean gestational age of the 44 infants was 26.6wk (range,23.7-32.0),birth weight was 747 g (440-981),and relative birth weight was -1.9 SD (-4.9 to 1.0). We determined placental 11β-HSD2 activity,baseline,and ACTH-stimulated cortisol and assessed illness severity by the Score of Neonatal Acute Physiology (SNAP). One standard deviation decrease in placental 11β-HSD2 activity corresponded to a 1.85 (95%CI 0.55 to 3.14; p = 0.006) unit increase in SNAP score and 2.9 mm Hg decrease in minimum mean arterial pressure (95%CI 0.3 to 5.6 mm Hg; p=0.03). Placental 11β-HSD2 activity was not associated with cortisol concentrations,although the confidence interval of the ACTH-stimulated cortisol was close to zero:1 SD increase corresponded to 17%(-18%to 49%) increase in ACTH-stimulated cortisol. Moreover,a 1 SD decrease in enzyme activity was associated with a hazard ratio for postnatal glucocorticoid treatment of 1.63 (95%CI 1.00 to 2.65); p = 0.05. In ELBW infants,lower placental 11β-HSD2 activity is associated with more severe early postnatal illness and hypotension. Although an association with baseline or ACTH-stimulated cortisol was not seen,possible relationships with other components of the hypothalamic-pituitary-adrenal axis remain to be determined.
