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О б з о р н ы е с т а т ь и АНДРОЛОГИЯ И ГЕНИТАЛЬНАЯ ХИРУРГИЯ 2 0 1 5 1 13 Дегидроэпиандростерон: биосинтез, метаболизм, биологическое действие и клиническое применение (аналитический обзор) Н. П. Гончаров, Г. В. Кация ФГБУ «Эндокринологический научный центр» Минздрава России; Россия, 115478, Москва, ул. Москворечье, 1 Контакты: Николай Петрович Гончаров goncharovn@endocrincentr.ru Представлена фундаментальная информация относительно метаболизма дегидроэпиандростерона (ДГЭА), его биологической роли и возможности использования для заместительной терапии. Рассмотрены видовые различия в синтезе ДГЭА в коре надпочечников. ДГЭА и ДГЭА-сульфат вырабатывают надпочечники только представителей отряда приматов, т. е. человека, высших и низших обезьян. Их синтез идет по Δ5-пути: холестерин → прегненолон → 17-гидроксипрегненолон → ДГЭА. Надпочечники других видов животных, включая крыс и мышей, не синтезируют ДГЭА. Вместе с тем определенные структуры мозга не только человека и обезьян, но и других животных синтезируют de novo ДГЭА и его предшественники, которые обозначаются как нейростероиды. Показано, что клетки Пуркинье, которые играют важную роль в формировании памяти и в процессе обучения, являются главным местом образования нейростероидов у млекопитающих и других позвоночных. Для выяснения возрастной динамики циркулирующего ДГЭА и других стероидов у человека нами проведено изучение его уровня в различные периоды постнатального развития. Пик образования гормона приходится на возраст 25-30 лет. В промежутке от 20 до 90 лет его уровень у человека падает на 90 %. Уровень кортизола в крови с возрастом не изменяется, что приводит к дисбалансу в соотношении кортизол/ДГЭА. Доказана определяющая роль ДГЭА как источника (предшественника) биологически активных половых стероидов: тестостерона, эстрадиола и эстрона в периферических тканях. Рассмотрены биодоступность и возможные механизмы взаимодействия гормона с физиологическими и патологическими процессами в организме человека и животных. В экспериментах на животных показана более высокая биодоступность ДГЭА при трансдермальном введении по сравнению с его приемом per os, так как в этом случае не происходит быстрая инактивация стероида в печени при первом пассаже. Большинство современных исследований у мужчин и женщин демонстрируют выраженную зависимость биодоступности ДГЭА в организме от способа введения препарата. The review presents the fundamental information on the metabolism of dehydroepiandrosterone (DHEA), its biological role and possibilities of its use for replacement therapy. There were studied species differences in the synthesis of DHEA in the adrenal cortex. It was found that DHEA and DHEA-sulfate are produced only by the adrenal glands of humans and monkeys, including lower monkeys. Their biosynthesis involves the following steps: cholesterol → pregnenolone → 17-hydroxypregnenolone → DHEA. The adrenal glands of other species, including rats and mice do not synthesize DHEA. At the same time, in certain brain structures not only in man and monkey, but also in other anima...

We have studied steroid hormone profiles in young men with normal body mass index suffering obesity and metabolic syndrome. They showed a consistent tendency toward a shift in blood aldosterone level to the upper normal level and beyond. It was higher in patients with metabolic syndrome than with obesity. The testosterone levels displayed the downward trend from normal through obesity to metabolic syndrome values. The main predictors of testosterone dynamics in the course of development of obesity and metabolic syndrome were insulin concentration and BMI. Dynamics of dehydroepiandrosterone levels followed that of testosterone. It significantly decreased in men with metabolic syndrome compared with health subjects. Young men presenting with obesity and metabolic syndrome did not experience changes in morning and evening cortisol levels in peripheral blood. The study revealed the relationship between aldosterone levels and the development of metabolic syndrome mediated through the body mass index and the direct relationship between metabolic syndrome and testosterone dynamics.

The objective of the present work was to estimate the possibility of using the ELISA technique for the quantitative analysis of the metanephrine and normetanephrine levels in urine and to determine the cross-off points for the discrimination between their normal and pathological values for the purpose of diagnostics of pheochromocytoma. Methylated derivatives of adrenaline and noradrenaline were measured in 3,234 urine sample obtained from the patients presenting with elevated arterial pressure, resistance to therapy, and adrenal mass lesions who had visited the inpatient and outpatient departments of the Endocrinological Research Centre during the past 4 years. The measurement of total metanephrine and normetanephrine (free plus deconjugated fractions) was performed using commercial ELISA kits (IBL, Hambutg, Germany). The content of normetanephrine over 612 mcg in daily urine samples was shown to be the borderline between the normal values and those suggesting diagnosis of pheochromocytoma. The sensitivity of this assay was 97,5% (95% CI 91,1-99,6%), specificity 100% (95% CI 93,8-100%). For metanephrine, the level of more than 550 mcg/24 hours was the borderline between the normal values and those suggesting diagnosis of pheochromocytoma. The sensitivity of the method was 100% (95% CI 88-100%), specificity - 96% (95% CI 86-99,4%). The biochemical diagnosis of pheochromocytoma was confirmed by the reference pathomorphological method in 99% of the cases. The incidence of pheochromocytoma predicted by the biochemical analysis of the urine samples delivered to the laboratory during 4 years from the patients with the tentative diagnosis of this pathology (based on the elevated arterial pressure and the presence of adrenal mass lesions) was 4% on the average. It is concluded that the application of ELISA in a "manual" mode provides high sensitivity and specificity of quantitative determination of metanephrines in daily urine comparable to those achieved with the widely used but more expensive high performance liquid chromatography.

The objective of the present study was to estimate the informative value of the measurements of aldosterone level, direct renin, and plasma renin activity as well as the relationships between these characteristics for differential diagnostics of various forms of hypertension and, first and foremost, of primary aldosteronism. We have examined a total of 162 patients. The results of differential tests were used to allocate them to a few groups including 41 patients presenting with primary aldosteronism, 52 ones with incidentalomas, 26 with essential hypertension, and 43 with various endocrine diseases and normal arterial pressure (control groups). The aldosterone levels, direct renin, and plasma renin activity were measured in blood samples taken in morning hours from the patients in the supine position. The aldosterone to plasma renin activity (A/PRA) and aldosterone to direct renin (A/DR) ratios were calculated. The elevated blood aldosterone level is currently believed to be the principal criterion for primary aldosteronism in the patients suffering arterial hypertension. The RIA technology is the method of choice for the measurement of aldosterone levels. The determination of the A/PR ratio significantly improves the detectability of the disease. The use of direct renin level instead of kinetic renin ensures the high efficacy of screening for primary aldosteronism and its early diagnostics. The cut-off point for the calculation of the A/PRA ratio to differentiate between primary aldosteronism and incidentalomas is 2160 pmol/mcg/hr (sensitivity 100%, specificity 97.8%) in comparison with the analogous cut-off point for the discrimination between primary aldosteronism and endocrine pathology without hypertension is 49 pmol/mU (sensitivity 100%, specificity 95%). The cut-off point for the calculation of the A/PR ratio to differentiate between primary aldosteronism and incidentalomas is 2160 pmol/mcg/hr (sensitivity 89.5%, specificity 99%) in comparison with the analogous cut-off point for the discrimination between primary aldosteronism and endocrine pathology without hypertension is 1432 pmol/mcg/hr (sensitivity 89.5%, specificity 100%). It is concluded that the results of determination of direct renin level in the blood plasma are independent of the endogenous angiotensinogen level, less variable and more reproducible than than the results of the measurement of plasma renin activity. The aldosterone to direct renin ratio may be used for the screening of primary aldosteronism.