Familial pattern of corticosteroids and their metabolism in adult human subjects - the Scottish adult twin study

Corticosteroids are important in the regulation of normal physiology and ar e key factors in regulating cardiovascular physiology and disease, the deve lopment of which is known to have a genetic component. However, there is Li ttle information on the extent to which plasma and urine steroid levels are determined by familial and genetic factors. We have examined basal and ACT H-stimulated plasma steroid levels and 24-h corticosteroid metabolite excre tion rates in 146 pairs of adult twins [75 monozygotic (MZ); 71 dizygotic ( DZ)]. Intraclass correlation coefficients were measured for all variables; several plasma steroid measurements were strongly related in both (MZ) and (DZ) twins, consistent with a familial pattern. These included basal levels of 11-deoxycortisol and aldosterone. ACTH-stimulated plasma aldosterone le vels were also significantly correlated, to a significant degree, in both M Z and DZ twins. The index of 11 beta-hydroxysteroid dehydrogenase activity (tetrahydrocortisol + allotetrahydrocortisol/ tetrahydrocortisone) and of t he more specific index of activity of the type 2 isoform of this enzyme (ur ine free cortisol/cortisone) also correlated, to a similar degree, in DZ an d MZ twins. In contrast, for the basal and ACTH-stimulated plasma concentra tions and 24-h urine excretion rates of several corticosteroids, there was evidence of significant heritability (H2), in that correlation in MZ twins was greater than in DZ. For example, basal plasma corticosterone concentrat ions (B) (H2 = 0.44), basal and stimulated Il-deoxycorticosterone concentra tions (DOC) (H2 = 0.44 and 0.41, respectively), stimulated 11-deoxycortisol concentrations (H2 = 0.53), and the index of 11 beta-hydroxylase activity DOC/B (H2 = 0.49) were all significantly heritable. For the urinary variabl es, 24-h tetrahydrodeoxycortisol (H2 = 0.59) and free aldosterone (H2 = 0.5 6) were significantly heritable. Our data provide the first evidence that p lasma and urine levels of important glucocorticoids and mineralocorticoids show a strong familial pattern, and in some instances, there is evidence of a genetic component to this. This suggests that corticosteroids have a pla usible role in essential hypertension that has a similar heritable componen t.