Diminished 11 Beta-Hydroxysteroid Dehydrogenase Type 2 Activity Is Associated With Decreased Weight and Weight Gain Across the First Year of Life.

Abstract

Objective: We have hypothesized that changes in GC metabolism leading to increased availability may impair growth. Design: This was a prospective, longitudinal study with clinical measurements and 24-hour urinary steroid metabolite analysis at 1, 4, 12, 26, and 52 weeks after delivery in mothers and their babies. Setting: The study was conducted with observations and samples collected in the volunteers’ own homes. Participants: Healthy mothers and newborn babies/infants participated in the study. Interventions: There were no interventions. Main outcome measures: Urinary steroid metabolite excretion quantified by gas chromatography/ mass spectroscopy across the first year of life in relation to change in weight was measured. Results: The total production of the GC metabolites quantified increased across the first year of life. Markers of 11ﰀ-hydroxysteroid dehydrogenase type 1 activity increased from the age of 3 months as did those of 5ﰂ-reductase activity. After correcting for confounding variables, low markers of 11ﰀ-hydroxysteroid dehydrogenase type 2 activity was associated with reduced absolute weight and decreased weight gain over the first year of life. In the mothers, 5ﰂ-reductase activity was low at birth and progressively increased to normal over the first 6 months postpartum. Conclusions: Increased GC exposure as a consequence of reduced 11ﰀ-hydroxysteroid dehydro- genase type 2 activity is likely to be a critical determinant of growth in early life. This not only highlights the central role of GCs and their metabolism, but also emphasizes the need for detailed longitudinal analyses.