Heritability of Cortisol Production and Metabolism Throughout Adolescence.

Britt J Van Keulen,Joost Rotteveel,Brian R Walker,Ruth Andrew,Martijn J J Finken,Hilleke E Hulshoff Pol,Conor V Dolan,Dorret I Boomsma

doi:10.1210/clinem/dgz016

Abstract

ContextInter-individual differences in cortisol production and metabolism emerge with age and may be explained by genetic factors.ObjectiveTo estimate the relative contributions of genetic and environmental factors to inter-individual differences in cortisol production and metabolism throughout adolescence.DesignProspective follow-up study of twins.SettingNationwide register.Participants218 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 measuresThe total contribution of genetic factors (broad-sense heritability) and shared and unshared environmental influences to inter-individual differences in cortisol production and activities of 5α-reductase, 5β-reductase, and 11β-hydroxysteroid dehydrogenases and cytochrome P450 3A4.ResultsFor 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 (5α-and 5β-reductases), broad-sense heritability increased with age (to >50%), while for the other indices (renal 11β-HSD2, global 11β-HSD, and CYP3A4), the contribution of genetic factors was highest (68%, 18%, and 67%, respectively) at age 12.ConclusionsThe 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.

Highlights

Cortisol, the main product of the hypothalamus-pituitary-adrenal (HPA) axis, is a crucial steroid hormone in the physiological stress response following homeostasis disturbance [1]
It has been recognized that experiences in early life may induce permanent alterations in the settings t of several endocrine systems, including the HPA axis [5,6]. rip There is a paucity of data on the magnitude of the contribution of genetic factors to variance in HPA c axis activity
The aim of the current study was to focus on indices of cortisol production and sc metabolism across adolescence, and to estimate the relative contributions of genetic and u environmental factors to cortisol production and metabolism in a sample of children who were n registered at birth in the Netherlands Twin Register (NTR)

Summary

Introduction

The main product of the hypothalamus-pituitary-adrenal (HPA) axis, is a crucial steroid hormone in the physiological stress response following homeostasis disturbance [1]. Dysregulation of HPA axis activity has been associated with cardiovascular diseases and psychiatric conditions, e.g., major depressive disorder, post-traumatic stress disorder, panic disorder, and chronic anxiety [2,3,4]. Rip There is a paucity of data on the magnitude of the contribution of genetic factors to variance in HPA c axis activity. Several studies in monozygotic (MZ) and dizygotic (DZ) twins addressed the relative s contributions of genetic and environmental factors on serum and salivary cortisol levels. Nu the magnitude of the heritability estimates varies (Table 1). A meta-analysis of five twin studies a published before 2001, of which 4 were conducted in adults and 1 in both children and adults, estimated the heritability of basal cortisol assessed in serum or saliva at 62% [7].

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