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Open access

Siphiwe N Dlamini, Zané Lombard, Lisa K. Micklesfield, Nigel Crowther, Shane A. Norris, Tracy Snyman, Andrew A Crawford, Brian R Walker, and Julia H. Goedecke

Circulating glucocorticoids are associated with the metabolic syndrome and related cardiometabolic risk factors in non-Africans. This study investigated these associations in Africans, whose metabolic phenotype reportedly differs from Europeans. Measures of adiposity, blood pressure, glycaemia, insulin resistance, and lipid profile, were measured in 316 African men and 788 African women living in Soweto, Johannesburg. The 2009 harmonized criteria were used to define the metabolic syndrome. Serum glucocorticoids were measured using liquid chromatography-mass spectrometry. Cortisol was associated with greater odds of presenting with the metabolic syndrome (odds ratio (95% confidence interval, 95%CI) =1.50 [1.04, 2.17] and higher systolic (beta coefficient, β (95%CI) =0.04 [0.01, 0.08]) and diastolic (0.05 [0.02, 0.09]) blood pressure, but higher HDL (0.10 [0.02, 0.19]) and lower LDL (-0.14 [-0.24, -0.03]) cholesterol concentrations, in the combined sample of men and women. In contrast, corticosterone was only associated with higher insulin sensitivity (Matsuda index; 0.22 [0.03, 0.41]), but this was not independent of BMI. Sex-specific associations were observed, such that both cortisol and corticosterone were associated with higher fasting glucose (standardized β (95%CI): 0.24 [0.12, 0.36] for cortisol; and 0.12 [0.01, 0.23] for corticosterone) and HbA1c (0.13 [0.01, 0.25] for cortisol; and 0.12 [0.01, 0.24] for corticosterone) in men only, but lower HbA1c (0.10 [ -0.20, -0.01] for cortisol; and -0.09 [-0.18, -0.03] for corticosterone) in women only. Our study reports for the first time that associations between circulating glucocorticoid concentrations and key cardiometabolic risk factors exhibit both glucocorticoid- and sex-specificity in Africans.

Open access

Britt J van Keulen, Conor V Dolan, Bibian van der Voorn, Ruth Andrew, Brian R Walker, Hilleke Hulshoff Pol, Dorret I Boomsma, Joost Rotteveel, and Martijn J J Finken

Objective

Sex differences in disease susceptibility might be explained by sexual dimorphism in hypothalamic-pituitary-adrenal axis activity, which has been postulated to emerge during puberty. However, studies conducted thus far lacked an assessment of Tanner pubertal stage. This study aimed to assess the contribution of pubertal development to sexual dimorphism in cortisol production and metabolism.

Methods

Participants (n = 218) were enrolled from a population-based Netherlands Twin Register. At the ages of 9, 12 and 17 years, Tanner pubertal stage was assessed and early morning urine samples were collected. Cortisol metabolites were measured with GC-MS/MS and ratios were calculated, representing cortisol metabolism enzyme activities, such as A-ring reductases, 11β-HSDs and CYP3A4. Cortisol production and metabolism parameters were compared between sexes for pre-pubertal (Tanner stage 1), early pubertal (Tanner stage 2–3) and late-pubertal (Tanner stage 4–5) stages.

Results

Cortisol metabolite excretion rate decreased with pubertal maturation in both sexes, but did not significantly differ between sexes at any pubertal stage, although in girls a considerable decrease was observed between early and late-pubertal stage (P < 0.001). A-ring reductase activity was similar between sexes at pre- and early pubertal stages and was lower in girls than in boys at late-pubertal stage. Activities of 11β-HSDs were similar between sexes at pre-pubertal stage and favored cortisone in girls at early and late-pubertal stages. Cytochrome P450 3A4 activity did not differ between sexes.

Conclusions

Prepubertally, sexes were similar in cortisol parameters. During puberty, as compared to boys, in girls the activities of A-ring reductases declined and the balance between 11β-HSDs progressively favored cortisone. In addition, girls showed a considerable decrease in cortisol metabolite excretion rate between early and late-pubertal stages. Our findings suggest that the sexual dimorphism in cortisol may either be explained by rising concentrations of sex steroids or by puberty-induced changes in body composition.