Figure 1.
Plasma cortisol (F) and cortisone (E) levels, and F/E ratio in mothers and their neonates.
A: Comparison of plasma cortisol and cortisone levels between mothers and neonates. Results for each parameter are expressed in ng/ml, as means ± SEM of the 43 values obtained from the mother-neonate couples. Plasma cortisol levels are significantly higher in mother than in neonates (*** p<0.001), and on the contrary, plasma cortisone levels are significantly lower (*** p<0.001). B: Comparison of the F/E ratio between maternal and neonatal plasma. The F/E ratio, which corresponds to cortisol metabolism by the 11βHSD2 enzyme, is significantly higher in mothers than in neonates (*** p<0.001). These results reflect a strong activity of the placental 11βHSD2.
Figure 2.
Urinary cortisol (F) and cortisone (E) concentrations and F/E ratio, in full-term newborns.
A: Comparison between F and E in neonatal urine. Results are expressed in ng/µg of urinary creatinine concentration, as means ± sem of the 44 values obtained in neonates. Cortisol levels are significantly lower than cortisone levels (*** p<0.001). B: Comparison between plasma and urinary F/E ratio in neonates and in 50 healthy control adults. No difference was observed between the F/E ratio in plasma and urine at birth, which could reflect an inactivity of the neonatal renal 11βHSD2. On the contrary this enzyme is very active in adults, with an inversion of the F/E ratio in urine, significantly different from the plasma ratio (*** p<0.001).
Figure 3.
11βHSD2 mRNA expression and activity throughout renal development in mice.
A: Relative mRNA expression in mice was determined using qPCR at various developmental stages, as follows : E 17.5, D 0.5 and D 8.5 E: Embryonic day, D: Postnatal day. Results, expressed as the ratio of attomoles of specific gene per femtomole of ribosomal 18S, correspond to mean ± SEM (E17.5 n = 9, D0.5 n = 17, D8.5 n = 6). *** p<0.001. B: Renal 11βHSD2 activity was determined at the same developmental stages and in adults, by measuring the rate of conversion of 3H-cortisol into 3H-cortisone, under three conditions : basal, with NicotinAmid Dinucleotid (NAD), with NAD and carbenoxolone, a specific 11βHSD2 inhibitor. Results, expressed as the ratio of picomoles of enzymatic activity after 2 hours per micrograms of protein, represent the mean ± SEM of three independent experiments for each developmental stage and each condition. * p<0.05; ** p<0.01, NS : Not Significant.
Figure 4.
11βHSD2 mRNA and protein expression throughout renal development in humans.
A: Relative mRNA expression in human fetal kidney samples at various gestational ages was determined using qRT-PCR at various gestational ages. Results are mean ± SEM of three independent determinations of 11βHSD2 mRNA expression, performed in triplicate for each sample. They are expressed as the ratio of attomoles of specific gene per femtomole of 18S, normalized by an internal calibrator. GW : gestational weeks. 14–16 GW n = 2, 19–24 GW n = 13, 25–40 GW n = 4. *** p<0.001. B: Immunodetection of the 11βHSD2 protein at 40 GW and at 1 year of age in human kidney samples. The 11βHSD2 protein is not detected in human kidney at birth whereas it is readily detected in the cytoplasm of cortical collecting duct cells at one year of age. Original magnification ×20.