Heritability of Cortisol Production and Metabolism Throughout Adolescence: A Twin Study

• Published in: The journal of clinical endocrinology and metabolism 2020-02, Vol.105 (2), p.443-452
• Main Authors: van Keulen, Britt J, Dolan, Conor V, Andrew, Ruth, Walker, Brian R, Hulshoff Pol, Hilleke E, Boomsma, Dorret I, Rotteveel, Joost, Finken, Martijn J J
• Format: Article
• Language: English
• Subjects: Adolescence; Adolescents; Age; Child development; Clinical s; Cortisol; Cytochrome P450; Environmental factors; Genetic aspects; Genetic factors; Health aspects; Heritability; Hormones; Hydrocortisone; Hypothalamic-pituitary-adrenal axis; Metabolism; Metabolites; Physiological aspects; Steroid 5α-reductase; Twins
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgz016

Context: Inter-individual differences in Cortisol production and metabolism emerge with age and may be explained by genetic factors. Objective: To estimate the relative contributions of genetic and environmental factors to inter-individual differences in cortisol production and metabolism throughout adolescence. Design: Prospective follow-up study of twins. Setting: Nationwide register. Participants: 218 mono- and dizygotic twins (N = 109 pairs) born between 1995 amd 1996, recruited from the Netherlands Twin Register. Cortisol metabolites were determined in 213, 169, and 160 urine samples at the ages of 9, 12, and 17, respectively. Main outcome measures: The total contribution of genetic factors (broad-sense heritability) and shared and unshared environmental influences to inter-individual differences in cortisol production and activities of 5[alpha]-reductase, 5[beta]-reductase, and 11[beta]-hydroxysteroid dehydrogenases and cytochrome P450 3A4. Results: For cortisol production rate at the ages of 9, 12, and 17, broad-sense heritability was estimated as 42%, 30%, and 0%, respectively, and the remainder of the variance was explained by unshared environmental factors. For cortisol metabolism indices, the following heritability was observed: for the A-ring reductases (5[alpha]-and 5[beta]-reductases), broad-sense heritability increased with age (to >50%), while for the other indices (renal 11[beta]-HSD2, global 11[beta]-HSD, and CYP3A4), the contribution of genetic factors was highest (68%, 18%, and 67%, respectively) at age 12. Conclusions: The contribution of genetic factors to inter-individual differences in cortisol production decreased between 12 and 17y, indicative of a predominant role of individual circumstances. For cortisol metabolism, distinct patterns of genetic and environmental influences were observed, with heritability that either increased with age or peaked at age 12y. (J Clin Endocrinol Metab 105: 443-452, 2020)