Endocrine Abstracts (2004) 7 P199

Glucocorticoids contribute to the heritability of leptin in Scottish adult female twins

AM Wallace1, E Banfield2, M Ingram3, L Swan3, WS Hillis3 & JMC Connell3


1Department of Clinical Biochemistry, Royal Infirmary, Glasgow, UK; 2Wellcome Trust Centre for Human Genetics, University of Oxford, UK; 3Division of Cardiovascular and Medical Sciences, University of Glasgow, UK.


There is considerable evidence to indicate that the hypothalamic-pituitary-adrenal axis is activated in obesity and that glucocorticoids may have a stimulatory effect on adipocyte leptin production. However, the precise interactions between glucocorticoids and leptin are complex and remain poorly understood. To investigate whether the glucocorticoid/leptin interaction is affected by genetic factors, we investigated the heritability of BMI, leptin and glucocorticoid metabolite excretion in monozygotic (MZ) and dizygotic (DZ) female twins.

We studied 93 female Scottish twins [54 (MZ): 39 (DZ)] and measured BMI, serum leptin (by RIA) and the pattern of and absolute amount of major urinary glucocorticoid metabolites [Tetrahydrocortisone (THE), Tetrahydrocortisol (THF) and alloTHF by GCMS]. Analysis was performed using the maximum likelihood analysis package Mx, developed by Neale1.

Leptin and BMI showed substantial heritability (68.3% and 71.3% respectively). Bivarate analysis indicated that the genetic determinants of BMI and leptin were partly shared. No correlation was found between leptin and the pattern of glucocorticoid excretion using THF + alloTHF/THE as an index of 11β-hydroxysteroid dehydrogenase activity. However, the heritability of leptin was significantly lower (63.8%) when values were corrected for the influence of glucocorticoid excretion expressed as a sum of major metabolites.

In summary, we have found that although the pattern of urinary glucocorticoid metabolites does not influence leptin heritability the total amount of glucocorticoid production does. These findings suggest that regulation of leptin reflects genetic/environmental and early life programming influences.

Reference.

1) Neale MC, Bocker SM, Xie G and Maes H.(2002) Mx:Statistical Modelling.

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