Background: Inter-individual differences in the metabolism of cortisol have been postulated to emerge during puberty, and might be explained by a complex interplay of genetic and environmental factors. The aim of the current study was to estimate the relative contributions of genetic, shared environmental, and unshared environmental factors on cortisol metabolism in a longitudinal twin cohort assessed at pre-pubertal, mid-pubertal and post-pubertal ages.
Methods: Males and females born between 1995 and 1996 were enrolled from a population-based twin register. Early-morning urine was collected at pre-pubertal (9 years), mid-pubertal (12 years) and post-pubertal (17 years) ages. Cortisol metabolites were measured, and ratios were calculated, representing the activities of various enzymes involved in cortisol metabolism. Data were analyzed using a model-fitting approach to obtain estimates of the relative influences of additive genetic effects, either dominance effects, or shared and non-shared environmental factors. Data were adjusted for batch and sex effects.
Results: 94 monozygotic and 124 dizygotic twins were included and 213, 167 and 162 samples were analyzed at pre-, mid- and post-pubertal ages, respectively. At these ages, the additive genetic (A), dominance (D), shared environmental (C) and unshared environmental influences (E) were estimated as: 5a-reductase-activity (allo-THF/cortisol): 9yr 14% (A), 45% (C), 41% (E), 12yr 39% (A), 39% (C), 22% (E), 17yr 26% (A), 24% (C), 50% (E), 5b-reductase-activity (THF/cortisol): 9yr 0% (A), 51% (C), 49% (E), 12yr model not suitable, 17yr 1% (A), 26% (D), 73% (E), 5b-reductase-activity (THE/cortisone): 9yr 40% (A), 32% (C), 28% (E), 12yr 19% (A), 42% (C), 39% (E), 17yr 26% (A), 25% (C), 50% (E), Renal 11b-HSD-type-2-activity (cortisol/cortisone) 9yr model not suitable, 12yr 60% (A), 8% (C), 32% (E), 17yr 4% (A), 34% (C), 63% (E), 11b-HSD-activity ((THE+allo-THF)/THE): 9yr 29% (A), 33% (C), 38% (E), 12yr 27% (A), 3% (D), 69% (E), 17yr 18% (A), 11% (C), 71% (E), Cytochrome-P450-activity (6-OH cortisol/cortisol): 9yr 13% (A), 22% (C), 65% (E), 12yr 56% (A), 9% (C), 35% (E), 17yr 26% (A), 28% (C), 46% (E).
Conclusion: There were considerable differences in the relative contributions of genetic and environmental factors to the ratios indicating activities of various enzymes involved in the metabolism of cortisol at pre-, mid- and post-pubertal ages. With few exceptions, the contribution of unshared environmental factors to these ratios was found to increase with age, implicating that individual circumstances seem to play a predominant role in later life.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology