Childhood obesity is accompanied by a variety of cardiovascular risk factors (hypertension, insulin resistance, dyslipidaemia) which tend to aggregate (syndrome X). 11beta-hydroxysteroid dehydrogenase (11beta-HSD) is supposed to play a role in the pathogenesis of hypertension and the development of syndrome X. There are two isoforms of 11beta-HSD. 11beta-HSD-2 is responsible for the inactivation of cortisol to inactive cortisone. In the case of impaired enzyme activity the ratio of urinary tetrahydrocortisol (THF)+ its isomer allotetrahydrocortisol (5alpha-THF)/tetrahydrocortisone (THE) is elevated. 11beta-HSD-1 is an oxo-reductase, which type catalyses the conversion of cortisone to cortisol. The aim of the present study was to investigate if there was any alteration in the urinary cortisol metabolites reflecting 11beta-HSD activity in hypertensive obese children (no.=15) as compared to normotensive obese (no.=11) and normotensive non-obese children (no.=15). We found an increased excretion of cortisol metabolites in hypertensive obese children compared to obese and normal - weight children having normal blood pressure. The ratio of THF+5alpha(THF/THE had a significant correlation with systolic blood pressure. On the basis of our study the ratio of THF+5alpha-THF/ THE reflecting on altered enzyme activity seems to be an independent factor influencing especially systolic blood pressure in hypertensive obese children.
In 1990, the worldwide accepted Shackleton method, which provides a possibility of determining the steroid metabolites from urine, was adopted in our laboratory. The procedure is very useful in the diagnosis of different endocrine diseases and in the recognition of dysfunction or absence of enzymes with an important role in steroid metabolism, and it gives possibility to control the treatment in patients with these diseases. Besides the proximate clinical application, the method gives a convenient tool to study the steroid background of these disorders, helping us understand the mechanism of their development. In the last few years, we have examined the steroid profile of patients with hair (androgen alopecia /AA/, effluvium /E/), psychiatric problems (major depression /MD/, eating disorders /EDS/, especially anorexia nervosa and bulimia) and osteoporosis (OP). In all of the examined hair loss diseases, the levels of main androgen metabolites were increased, and elevated 5alpha-reductase activity were found. We could observe the alteration of the activity of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) enzyme and marked gender differences in the changes of the steroid metabolism in patients with major depression (MD). In women with OP, the significantly decreased level of certain metabolites points to the role of testosterone, androstenedione and DHEA in postmenopausal bone loss in women. Our experiences contribute to the knowledge of the nature and steroid background of some endocrine and psychiatric diseases.
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