Relationships between secretion of pituitary gonadotropic hormones, adrenal glucocorticoid and androgenic function, and ovarian steroid production were studied in 14 patients with the polycystic ovaries syndrome (POS) under conditions of suppressed endogenous gonadotropic secretion, which was induced by tonic administration of busereline, a GnRH agonist. The bRH/iRH ratio is not changed in POS patients under conditions of suppressed gonadotropic secretion. Inhibition of gonadotropic secretion leads to decrease of estrogen secretion in the ovaries and does not affect the adrenal glucocorticoid function. Activation of adrenal androgen production by the delta-5 pathway was observed in 57% patients under conditions of gonadotroph inhibition. Three months after busereline was discontinued, adrenal steroidogenesis normalized. The results permit a conclusion that prolonged inhibition of gonadotropic secretion with GnRH agonist does not change the bLH/iLH ratio but can lead to activation of adrenal androgen production in part of patients with POS.
Цель. Изучение влияния андрогенного дефицита на эритропоэз и коррекция его с помощью комбинированной терапии препаратами эритропоэтина и тестостерона. Материалы и методы. В исследование включено 43 мужчины с сахарным диабетом 1 типа, получающих терапию ПГД. Пациенты были разделены на 2 группы в соответствии с возрастным критерием: группа 1 ? моложе 40 лет; группа 2 ? старше 40 лет. Всем пациентам проводилось определение антропометрических показателей (рост, вес, индекс массы тела). Выполнена оценка состояния углеводного обмена, гемопоэза. Для оценки андрогенного дефицита выполнено исследование уровней: лютеинизирующего гормона (ЛГ), ОТ, секс-стероид, связывающего глобулина (СССГ). Дополнительно мужчинам у которых выявлялось снижение уровня тестостерона, проводилось исследование уровня пролактина в крови . Результаты. При распределении мужчин по возрастным группам получены данные, демонстрирующие, что прогрессивное снижение концентрации Т с возрастом не сопровождается повышением уровня ЛГ выше нормы ? это свидетельствует о вторичности процесса или о нарушении механизма отрицательной обратной связи. Полученные в исследовании данные позволили установить, что андрогенный дефицит и его коррекция не влияли на компенсацию сахарного диабета. Получено значимое увеличение уровня гемоглобина на 16,2% у мужчин, которые получали комбинированную терапию. Заключение. андрогенный дефицит у мужчин, получающих лечение ПГД, является широко распространенным состоянием. Более выраженное влияние терапии препаратом Т получено в старшей возрастной группе с лабораторно подтвержденным андрогенным дефицитом.
The daily time course of changes In the secretion of dehydroepiandrosterone, its sulfate, and Cortisol, as well as their precursors (17-α-hydroxypregnenolone, 17-α-hydroxyprogesterone, and 11-deoxycortisol) was studied in patients with Itsenko-Cushing syndrome and disease. The mean daily blood concentrations were calculated for each hormone. The activity of the enzymatic systems of steroidogenesis was estimated from the ratio of the mean daily concentrations of the precursor of an enzymatic reaction to those of its product. The findings suggest that production of elevated concentrations of corticosteroids (both Cortisol and androgens) through the Δ5-pathway with the enhanced activity of 11β-hydroxylase and sulfatase is characteristic of patients with Itsenko-Cushing disease. In patients with Itsenko-Cushing syndrome, the generation of higher Cortisol levels is accomplished through the Δ4-pathway whereas the synthesis of androgens through the Δ5-pathway is minimal due to the decreased activity of 17,20-desmolase.
The serum concentration of total testosterone were measured in 100 male patients aged 19-65 years who had visited the clinic and polyclinic of the Endocrinology Research Center, Russian Academy of Medical Sciences for complaints about different dysfunctions of the endocrine glands. Testosterone was measured by the well-known currently available technologies: automatic Vitros ECi, Architect, and Access multianalyzers, manual Delfia and DRS enzyme immunoassay kits, and radioimmunoassay (RIA) that had been developed within the framework of the WHO Human Reproduction Programme and adjusted by the reference assay (gas chromatography/mass spectroscopy). The closest results were obtained when determining the level of testosterone by RIA and by means of the Vitros ECi multianalyzer (13.1 vs 13.0 nmol/l, medians). All other technologies demonstrated a low correlation with RIS and had positive biases, especially with the use of the Delfia kits (as high as 60 and, at low concentrations, 100%). The positive bias tends to decrease in patients with higher testosterone levels ( > 10 nmol/l) for all studied methods.
The study was undertaken to assess a potential risk of the elevated levels of dioxins in the town of Chapayevsk on reproductive function in adolescents during sexual maturation and in adults. It was ascertained that there was a regular trend for retarded sexual development by the Tanner stages in the adolescents living in the polluted areas as compared with control individuals of the same age. The incidence of cryptorchidism, varicocele, and inguinal hernias was 2-3 times higher in the boys from Chapayevsk than in those from Samara. However, the level of gonadotropic hormone was much higher in the Chapayevsk adolescents than that in the control group. Polluted area-living males with normal levels of reproductive hormones showed a drastic deterioration in the quality of sperm, mainly the morphological index with a characteristic reduction of the acrosomal area of the head of spermatozoons. They also displayed a decrease in the levels of dehydroepiandrosterone (DHEA) sulfate and increases in the level of cortisol and in cortisol/ DHEA sulfate ratios. The above deviations in the balance of corticosteroids suggest impaired adaptive homeostasis, which is one of the mechanisms responsible for a potential human health risk of polychlorinated hydrocarbons.
Relationships between the secretion of gonadotropic hormones of the pituitary gland, the androgenic and glucocorticoidal functions of the adrenals and the steroidogenic function of the ovaries were studied in 21 patients with the ovarian polycystic syndrome (OPS) and in 7 healthy women in test with buserelin, a gonadotropin-releasing agonist. When stimulated with corti- sole, the secretion remained unchanged. Depending on the baseline level of dehydroepiandrosterone sulfate (DHAS), a change was found in the secretion of dehydroepiandrosterone (DHA) and its precursor 17-OH-pregnenolone. With the normal baseline level of DHAS, the content of hormones increases while with its high level, their content does not change. The stimulation of gonadotropic secretion results in a higher dissociation in the secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in patients with OPS, by increasing the LH/FSH ratio that is most significant in patients with the normal level of DHAS. Under stimulation, aromatase activity becomes higher in patients with high DHAS levels and remains unchanged in the other group of patients. The findings may lead to the conclusion that buserelin-induced stimulation of gonadotropic secretion may be accompanied by the activated synthesis of adrenal androgens in some patients with OPS. Depending on the baseline androgenic activity of the adrenals, buserelin-induced stimulation of gonadotropic secretion is attended by a higher aromatase activity.
The papers examines the specific features ofsteroidogenesis in the adrenal cortex ofpatients with different types of tumors and analyzes the ratio of ∆4- to ∆5-pathways of corticosteroid biosynthesis, which is a governing factor in the development of adrenal cortical hyperfunction. The levels of all major corticosteroids (cortisol, aldosterone, androgens of the adrenals) and their precursors were studied in the peripheral blood of patients with corticosteroma, aldosteroma, androsteroma, and hormonally inactive tumors (in the morning and in the evening). Based on the calculation of the mean daily concentration of steroids and the ratio of product/substrate of an enzymatic reaction in the biosynthesis of corticosteroids, the authors determined the activity of some enzymes and analyzed the changes found in this activity as compared with the normal values. The findings indicate that in corticosteroma, the higher activity of 11β-hydroxylase and the lower activity of 17,20-desmolase leads to a biosynthesis shift to ∆4-pathway; in virilizing tumor, the enhanced activity of Зβ-olsteroid dehydrogenase results in the same shift; in aldosteroma, the ratio of biosynthesis pathways does not differ from the normal values. The significant scatter in the individual values when the blood concentrations were determined in patients with hormonally inactive tumors fails to make an unambiguous conclusion about the activity of steroidogenic enzymes and about the direction of biosynthesis in these patients.
Sixty-nine males aged 18-57 years, who had different impaired reproductive function and the body mass index (BMI) in the range of 20 to 40 kg/m2, were examined. In the patients, the baseline values of leptin, cortisole, corticosterone, dehydroepiandrosterone (DHA) and dehydroepiandrosterone sulfate (DHAS), progesterone, 17-hydroxyprogesterone, testosterone, and insulin were measured by using current radioimmunoassay and enzyme immunoassay. In the examinees, the mean values of all the hormones varied in the physiological normal range with deviations being in some patients. The patients with higher leptin levels were found to have also elevated adrenal hormones, such as corticosterone, cortisole, DHA and DHAS vice versa. This was not accompanied by differences in BMI and in the levels of insulin and testosterone. Analysis of the content of hormones in relation to the level of insulin indicated that there is a positive correlation of the level of insulin and leptin. However, this relationship was multifactorial, which had a possible modifying effects of BMI and the level of testosterone.
Hormonal and semen parameters in 416 men aged 25-45 years were examined: 328 were men who cleaned the territory around the Chernobyl nuclear reactor (called 'liquidators') and 88 were healthy age-matched controls. The dose of radiation received by the liquidators was 0.16 +/- 0.08 Gy. LH, FSH, prolactin, testosterone and cortisol levels were assayed using WHO-matched reagents. Semen analyses were performed according to the WHO Manual (1992). The mean concentration of all hormones in liquidators and controls were within the WHO-defined normal range. The mean levels of LH and cortisol in liquidators were significantly lower (p = 0.013 and p < 0.001, respectively) and testosterone significantly higher (p = 0.023) than in controls. The variations in hormone levels in liquidators were not correlated with the acquired doses of radiation as measured by personal dosimeters (film badges). Semen parameters in a subgroup of 70 liquidators were within the normal WHO-defined range. The percentage of normal forms of spermatozoa in liquidators (35.0 +/- 13.1%) was significantly lower (p < 0.015) than in a control group (42.8 +/- 8.9%). The study has shown that exposure of men to relatively short-term radiation did not cause long-lasting disruption of their endocrine status and spermatogenesis. The study was 7-9 years retrospective and it is therefore impossible to infer what the immediate effects of the radiation exposure were on these parameters.
The purpose of this work was to study metabolism and peripheral blood content of the main adrenal and gonadal androgens (dehydroepiandrosterone (DHEA) and DHEA sulfate and testosterone, respectively) in men of different age treated by insulin. Thirty-five diabetics type I aged 15-52 years and 34 age-matched healthy controls were examined. The levels of DHEA and DHEA sulfate in the peripheral blood were decreased in the diabetics in comparison with healthy men, the differences being the most pronounced at the age of 15-45years. In parallel with this, hydrocortisone levels were increased in the patients. Opposite changes in the levels of adrenal androgens and hydrocortisone cause a drastic shift in these hormones balance in the patients with type I diabetes. The content of testosterone was normal (20.6 ± 1.2 nmol/liter) in 28 of 35patients during insulin therapy, while in 7 with higher glycaemia values the mean testosterone content was no higher than 6.3 + 1.1 nmol/liter. Presumably, the content of testosterone remains normal in diabetics during insulin therapy in the presence of adequate metabolic control, while the content of adrenal androgens decreases
The purpose of present investigation was to determine the relationship of leptin level with BMI, insulin, sex hormones and C21 steroids in men with different reproductive failure. We studied 69 patients (33+/-1 yr.) with BMI 20-40 kg/m(2), insulin 2.7-117 mU/L, testosterone (T) 1.9-36.8 nmol/L, LH 0.6-41 IU/L, FSH 0.5-33.5 IU/L, cortisol 114-1389 nmol/L, corticosterone 5.7-72.6 nmol/L, DHEA 8-61.3 nmol/L, DHEAS 0.9-7.8 mumol/L and leptin 0.8-106 ng/ml. Significant positive correlations were observed between leptin and BMI (p=0.021), insulin (p=0.02), corticosterone (p=0.045), DHEA (p=0.007), DHEAS (p=0.01), LH (p=0.000), FSH (p=0.001) and negative one with testosterone (p=0.0044). In non-obese patients cortisol, corticosterone, DHEA, DHEAS are more powerful predictors of leptin variations than sex hormones. In obese patients 67% of leptin variations are affected by LH, and testosterone levels and BMI. In obese men with low testosterone levels LH is the most powerful positive modulator of leptin levels.
Daily changes in aldosterone secretion and its mean daily blood level were studied in patients with Icenko-Cushing disease with and without arterial hypertension and the relationship between aldosterone secretion, plasma renin activity, and blood hydrocortisone and ACTH level in such patients were studied. Two groups of patients with Icenko-Cushing disease were examined: with and without pronounced hypertension. Serum aldosterone, hydrocortisone, ACTH, and plasma renin activity were radioimmunoassayed simultaneously. Blood samples were collected at 8.00, 16.00, and 23.00, and the mean concentrations of hormones were calculated. Increase of hydrocortisone secretion was paralleled by increased secretion of aldosterone. Daily time course of blood aldosterone concentrations in patients with Icenko-Cushing disease complicated by hypertension was paradoxical: they were maximum in the evening and night hours. Development of hypertension in patients with Icenko-Cushing disease was closely associated with the duration and severity of disease and patient’s age.
The level of leptin production was measured in relation to the concentrations of adrenal androgens, testosterone, and gonadotropins in patients with various disorders of the male reproductive system and obesity. LH, FSH, prolactin, testosterone, estradiol, hydrocortisone, dihydroepiandrosterone (DHEA) and DHEA sulfate were radioimmunoassayed and leptin was measured by enzyme immunoassay. Body weight index (ВИД) in 66 examined patients varied from 20 to 40 kg/m2 and leptin content from 0.8 to 106 ng/ml. In general, the level of leptin directly correlated with the levels of BWI, LH, FSH, and DHEA sulfate and inversely with testosterone level. The highest levels of leptin were observed in patients with obesity combined with androgenic insufficiency, while in patients with obesity or androgenic insufficiency alone leptin levels were lower. No significant differences in leptin concentrations in relation to gonadotropin levels were detected. Normal fluctuations in the levels of adrenal androgens did not affect leptin production. These data indicate a possible involvement of testosterone in regulation of leptin production.
This paper reports the findings of search for probable hormone markers needed for diagnosis and choice of treatment strategy for patients with adrenal tumors without characteristic endocrine symptoms. Thirty women and 11 men with hormonally inactive tumors (HIT) and a control group matched for age and sex were examined. Steroid hormones were radioimmunoassayed. Tumor sizes varied from 1.3 to 10 cm according to ultrasonic examination, computer tomography, and results of surgery. The concentrations of the main steroid hormones and their precursors were virtually the same in patients with light-cell adenoma, HIT without morphological diagnosis, and controls. Some patients had high levels of corticosterone, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfonate (DHEA-S), which indicates the presence of adrenal hormonally-active tumors which were not diagnosed by standard hormone analysis including measurements of hydrocortisone and aldosterone. These data necessitate addition of measurements of corticosterone, DHEA, and DHEA-S in the protocol of examination of patients with HIT.
Endocrine parameters and spermatogenesis values were assessed in 328 men aged 25-45 years who participated in liquidation of the Chernobyl aftermath and in 88 age-matched healthy controls. The mean radiation dose in liquidators was 0.16+0.006 Gy. LH, FSH, prolactin, testosterone, and hydrocortisone were radioimmunoassayed using standard WHO reagents. Spermograms were analyzed according to WHO recommendations (1992). The mean hormone levels in the blood of liquidators were within the normal range and did not differ from those in the controls. Individual deviations in hormone content did not correlate with radiation dose and their incidence was compatible with that in the control group. The most frequent disorders of spermatogenesis in the liquidators were teratospermia (29%) and oligospermia (23%). Spermogram abnormalities did not depend on the absorbed dose. Thus, there are no appreciable shifts in the mechanisms of endocrine regulation of the reproductive function and in spermatogenesis 7-9 years after radiation exposure.