Serum Dehydroepiandrosterone Sulfate Concentrations Research Articles

Antidepressant Treatment and Dehydroepiandrosterone Sulfate: Different Effects of Amitriptyline and Paroxetine

Background: There is evidence for activation of the hypothalamus-pituitary-adrenal system in depressed patients to be associated with increased secretion of adrenal androgens. However, there is only limited information about the effect of different classes of antidepressants on the course of adrenal androgens. Methods: Dehydroepiandrosterone sulfate (DHEA-S) serum concentrations were measured in 80 patients being treated with amitriptyline (AMI) or paroxetine (PAROX) for a period of 35 days. Results: Using analysis of variance with repeated measures, we found a significant effect of treatment upon DHEA-S serum concentrations that declined more in AMI-treated (before vs. after: 1.89 ± 1.16 vs. 1.46 ± 0.96 mg/l), compared to PAROX-treated patients (1.56 ± 1.09 vs. 1.50 ± 1.04 mg/l). Conclusions: Our results show changes in DHEA-S serum concentrations during antidepressant treatment to depend on medication.

Association of the (AU)AT-rich element polymorphism in PPP1R3 with hormonal and metabolic features of polycystic ovary syndrome.

Insulin resistance, a key factor in the pathogenesis of polycystic ovary syndrome (PCOS), is associated with a reduction in activation of muscle glycogen synthase. A 5-bp insertion-deletion polymorphism in the (AU)AT-rich element (ARE) within the 3'-untranslated region of the gene encoding the muscle-specific glycogen-targeting subunit of protein phosphatase 1 (PPP1R3) has been associated with insulin resistance and type 2 diabetes. The present study was undertaken to examine the relationship of the ARE polymorphism with clinical and hormonal characteristics of women with PCOS. We studied 186 women with PCOS who had undergone a standard 75-g oral glucose tolerance test and measurement of serum androgen and SHBG levels. Among the largest cohort of nondiabetic subjects (Caucasian, n = 112), the presence of the deletion allele (ARE-2) was associated with insulin resistance and hyperandrogenemia. There was no association of the ARE polymorphism with body mass index or blood glucose concentration during the oral glucose tolerance test. Subjects who were homozygous for the insertion allele (ARE-1/1) had a mean insulin area under the curve (99,116 +/- 6,625 pmol/liter.min) that was significantly lower than that in either the heterozygous (ARE-1/2) (132,195 +/- 12,340 pmol/liter.min) or homozygous (ARE-2/2) (164,661 +/- 24,219 pmol/liter.min) deletion groups. In addition, ARE-1/1 subjects had significantly lower serum concentrations of dehydroepiandrosterone sulfate compared with ARE-2/2 subjects (4.2 +/- 0.3 vs. 6.6 +/- 0.7 micromol/liter) and a trend toward lower levels of free testosterone (78.8 +/- 6.5 vs. 114.1 +/- 30.8 pmol/liter). Studies of diabetic and nondiabetic PCOS women of other racial and ethnic backgrounds will be necessary to assess the impact of this and other variants in PPP1R3 upon the phenotype and natural history of women with PCOS.

Resting serum dehydroepiandrosterone sulfate level increases after 8-week resistance training among young females.

This study examined changes among young females of resting serum dehydroepiandrosterone sulfate (DHEAS) concentration after an 8-week period of resistance training. Nineteen healthy untrained young females [training group: age 18.9 (0.3) years, n=10, control group: age 19.3 (1.0) years, n=9; mean (SD)] were recruited in this study. The training group participated in an 8-week resistance training program (2 days per week on nonconsecutive days). The control group did not involve in any resistance training or regular exercise during the study period. Muscular strength, anthropometry, and resting hormonal levels were measured before and after training in both groups. Serum concentrations of DHEAS, dehydroepiandrosterone (DHEA), testosterone and cortisol were measured by radioimmunoassay. Body mass (2.4%) and lean body mass (2.4%) were significantly increased in the training group ( P<0.05), but not in the control group. The training also significantly increased one-repetition maximum (1-RM) values ( P<0.05). In the training group, resting concentration of serum DHEAS significantly increased after training ( P<0.05). Percent change of DHEAS in the training group was greater than that of the control group ( P<0.05). In the training group, the change of DHEAS level was positively correlated with the change of lean body mass during the training ( r=0.61; P<0.05). Serum DHEA, testosterone and cortisol concentrations did not change in either group during the training. The dramatic increase of resting serum DHEAS concentration after training indicates that DHEAS might be an anabolic hormone marker of adaptation to resistance training among young females. Results are presented as mean (SD).

Serum concentrations of dehydroepiandrosterone sulfate and leptin in obese patients with normal serum cholesterol

Normal (< 200 mg/dL) serum concentrations of cholesterol and a favorable ratio of cholesterol/high-density lipoprotein (HDL)-cholesterol are frequently seen in morbidly obese (body mass index [BMI] > 35 kg/m2) patients. Because it is unknown whether this subgroup is characterized by differences in other potential markers of cardiovascular disease, serum concentrations of dehydroepiandrosterone sulfate (DHEAS) and leptin were determined in 155 obese patients (BMI > 35 kg/m2, aged 20 to50 years) with normal (n = 72) or with elevated (n = 83) total serum cholesterol. We found that seemingly negative marginal correlations between serum concentrations of DHEAS and cholesterol, as well as between DHEAS and the ratio cholesterol/HDL-cholesterol, were not any more apparent after correction for age, sex, and BMI. A negative correlation between serum leptin concentrations and the ratio cholesterol/HDL-cholesterol persisted after correction for age, sex, and BMI. In morbid obesity, there appears to be an association between serum concentrations of leptin and a more favorable lipid profile, whereas there is no direct interrelation between serum concentrations of cholesterol and DHEAS. Copyright 2003, Elsevier Science (USA). All rights reserved.

Dehydroepiandrosterone sulfate and growth axis hormones in patients after surgery.

We selected 38 patients scheduled for cholecystectomy and studied their serum concentrations of dehydroepiandrosterone (DHEA) and growth axis hormones [growth hormone/insulin-like growth factor-1 (GH/IGF-1)]. We aimed to determine whether alterations in these concentrations resulted from surgical stress or, on the contrary, preceded surgery and were themselves a cause of chronic diseases that reduce life expectancy. We measured the serum concentrations of DHEA sulfate (DHEA-S), ACTH, cortisol, human GH (hGH), IGF-1, and IGF-1 binding protein-3 (IGFBP-3) preoperatively and then 2 and 7 days after surgery; we also compared the preoperative findings with those of a healthy control group. The results were analyzed by gender because DHEA and GH/IGF-1 are known to present sexual dimorphism. There were no significant differences between the preoperative and control results for any of the parameters studied. We found a significant reduction in the concentrations of DHEA-S and IGF-1 on days 2 and 7 after surgery versus the preoperative values. We conclude that the decrease in DHEA-S in patients after surgery is a result of surgical trauma and does not precede surgical stress. The decrease in hormone levels observed in patients with chronic disease may therefore be a result, not a cause, of disease, as some have claimed. Further studies with a later endpoint would be of interest to assess any subsequent return of DHEA-S levels to baseline measurements.

Adrenopause or decline of serum adrenal androgens with age in women living at sea level or at high altitude.

The present study aimed to determine adrenopause or reduction of serum adrenal androgens with age at high altitude and at sea level. It was a cross-sectional study performed in 210 women resident at high altitude (4340 m) and 123 women living in Lima (150 m), aged 20-70 years. Fasting early morning blood samples were obtained. Serum dehydroepiandrosterone (DHEA), DHEA sulphate (DHEAS), androstenedione, testosterone and estradiol were measured by radioimmunoassay. Serum testosterone concentrations were greater in women living at high altitude than in those resident at sea level. Serum concentrations of DHEA, DHEAS and androstenedione were lower in women living at high altitude than in those living at sea level. The DHEAS/DHEA ratio was significantly greater, and the androstenedione/testosterone ratio was lower in samples from women living at high altitude. Among women older than 50 years of age, a greater decline in serum concentrations of DHEA was observed in those living at high altitude than in those living at sea level. Among women 60-70 years of age, serum concentrations of DHEA at high altitude were 46.9% of those in women of the same age living at sea level. Decay of DHEAS at sea level and at high altitude occurred from the age of 40 years. The decline was faster at high altitude than at sea level, and in women aged 60-70 years serum values of DHEAS at high altitude were 56% of those at sea level. In the same age group, serum concentrations of androstenedione among those native to high altitudes were 27.34% of the value at sea level. At sea level, serum testosterone concentrations did not change with age from 20 to 70 years. In women aged 20-39 years and 50-59 years, serum testosterone concentrations were greater at high altitude than at sea level (P<0.05). In those aged 60-70 years, the concentrations were similar in those living at sea level and at high altitude. At sea level and at high altitude, the serum testosterone/estradiol ratio increased with age (P<0.0034 and P<0.0001 respectively). This ratio increased at an earlier age among those living at high altitude (40-49 years) than among those living at sea level (50-59 years). Multivariate analysis showed that altitude (P<0.0001) and greater chronological age (P<0.001) were associated with lower serum DHEAS concentrations. DHEAS was related to chronological age (P<0.0001). Low serum androstenedione concentrations were related to living at high altitude at birth and greater chronological age (P<0.0001). In conclusion, adrenopause is attained earlier and is of greater magnitude at high altitude than at sea level.

Genetics of Serum Dehydroepiandrosterone Sulfate and Its Relationship to Insulin in a Population-Based Cohort of Twin Subjects

Previous studies have shown a significant effect of insulin administration on serum dehydroepiandrosterone sulfate (DHEA-S) concentration and its metabolic rate, with evidence for the effect in men, but not in women. This could lead to differences in the sources of variation in serum DHEA-S between men and women and in its covariation with insulin concentration. This study aimed to test whether these hypotheses were supported in a sample of healthy adult twins. Serum DHEA-S (n = 2287) and plasma insulin (n = 2436) were measured in samples from adult male and female twins recruited through the Australian Twin Registry. Models of genetic and environmental sources of variation and covariation were tested against the data. DHEA-S showed substantial genetic effects in both men and women after adjustment for covariates, including sex, age, body mass index, and time since the last meal. There was no significant phenotypic or genetic correlation between DHEA-S and insulin in either men or women. Despite the experimental evidence for insulin infusion producing a reduction in serum DHEA-S and some effect of meals on the observed DHEA-S concentration, there were no associations between insulin and DHEA-S at the population level. Variations in DHEA-S are due to age, sex, obesity, and substantial polygenic genetic influences.

Diurnal rhythm and effects of oral contraceptives on serum dehydroepiandrosterone sulfate (DHEAS) are related to alterations in serum albumin rather than to changes in adrenocortical steroid secretion

Dehydroepiandrosterone sulfate (DHEAS), which is of almost exclusive adrenal origin, is important for the androgen status in women and prepubertal children, and DHEAS assays are used in the investigation of hyperandrogenism. There are conflicting reports concerning a diurnal variation in serum DHEAS. Although of adrenocortical origin, serum DHEAS levels are decreased by oral contraceptives (OCs). DHEAS is strongly bound to serum albumin and has a very low metabolic clearance rate. The present study was performed in order to investigate whether a diurnal variation in serum DHEAS exists and, if so, whether this diurnal variation and the decreased DHEAS levels following OC use are related to alterations in adrenocortical steroids or to changes in serum albumin. Serum concentrations of DHEAS, dehydroepiandrosterone (DHEA), cortisol and albumin were determined in blood samples taken every half hour over a 24-h period in 10 healthy women before and during use of combined OCs. Significant and frequently synchronous diurnal variations in serum DHEAS and albumin were found before as well as during OC use. These variations were not synchronous with the diurnal variation in DHEA. OCs significantly decreased serum DHEAS and albumin levels. A multiple regression analysis showed changes in albumin to be the most decisive factor for the diurnal variation as and for OC-induced changes in DHEAS. Changes in serum DHEAS during the day and following OC use are related to alterations in its main binding protein, serum albumin, rather than to changes in adrenocortical steroid secretion.

Serum Dehydroepiandrosterone Sulfate Concentration as an Indicator of Adrenocortical Suppression in Asthmatic Children Treated with Inhaled Steroids

ACTH regulates adrenal androgen production, which may thus be reduced during glucocorticosteroid therapy. Dehydroepiandrosterone sulfate is the most abundant androgen secreted by the adrenals. We wished to evaluate whether serum levels of dehydroepiandrosterone sulfate can be used as an indicator of adrenal suppression during inhaled steroid treatment in children. Sixty school-aged children with newly diagnosed asthma were randomly divided into budesonide (n = 30) and fluticasone propionate (n = 30) groups. Fifteen cromone-treated children served as a control group. The budesonide dose was 800 μg/d during the first 2 months and 400 μg/d thereafter. The respective fluticasone propionate doses were 500 and 200μ g/d. Serum dehydroepiandrosterone sulfate concentrations were measured before and after 2 and 4 months of treatment. In the budesonide group, serum dehydroepiandrosterone sulfate decreased from the baseline by a mean of 21% (95% confidence interval, 13–29%; P < 0.001) after 2 months of high dose treatment and by 16% (95% confidence interval, 8–25%; P < 0.001) after 4 months of treatment. In the fluticasone propionate group, the respective figures were 10% (95% confidence interval, 4–16%; P < 0.01) and 6% (95% confidence interval, 16% decrease–3% increase; P = NS). A low dose ACTH test indicated adrenocortical suppression at 4 months in 14 (23%) steroid-treated children. In these children, dehydroepiandrosterone sulfate decreased by a mean of 21% (95% confidence interval, 14–28%), whereas in those 46 steroid-treated children with normal ACTH test results, dehydroepiandrosterone sulfate decreased by 8% (95% confidence interval, 0–16%; P < 0.05 between these groups). In the control group, dehydroepiandrosterone sulfate levels tended to increase (by a mean of 26%), reflecting the normal physiological change at this age. In conclusion, inhaled steroid treatment suppresses dehydroepiandrosterone sulfate production in a dose-dependent manner. Monitoring of serum dehydroepiandrosterone sulfate concentrations can be used as a practical method to follow adrenocortical function and to detect its suppression during inhaled steroid treatment in children.

Effects of hormone replacement therapy on endocrine and spirometric parameters in asthmatic postmenopausal women

The aim of the study was to see if there are any correlations between changes in the endocrine system and clinical condition of asthmatic patients ,in particular their lung function ,caused by hormone replacementtherapy (HRT). Fifty-five asthmatic and 20 healthy postmenopausal women (aged 48–60) were studied before HRT and after 6 months of cyclical transdermal 17β-estradiol and medroxyprogesteroneacetate treatment. Serum estradiol ,cortisol and dehydroepiandrosterone sulfate (DHEAS) concentrations were assessed with the use of RIA ,and spirometry parameters were measured.Statistically significantdiminution of asthma exacerbations ,reduced consumption of inhaled glucocorticosteroids and improvement in all investigated spirometry parameters was shown in patients treated with glucocorticosteroidsduring HRT. A reduction in mean 24-hour serum estradiol levels in asthmatic women was noted ,whereas cortisol and DHEAS serum concentrations were decreased in asthmatic patients treated with glucocorticosteroidscompared with the control group ,before HRT. HRT produced increases in the concentrations of estradiol ,cortisol and DHEAS in serum. Significant positive correlations were noted between estradiol concentrationsand small and medium bronchi tests.In conclusion ,HRT in postmenopausal asthmatic women has a favorable influence on the course of asthma ,reduces daily use of glucocorticosteroids and frequency ofasthma exacerbations and normalizes serum concentrations of estradiol ,cortisol and DHEAS ,which were decreased before HRT.

Serum dehydroepiandrosterone sulfate concentrations across the life span of laboratory-housed rhesus monkeys.

Cross-sectional studies of humans have shown that dehydroepiandrosterone sulfate (DHEAS) peaks shortly after sexual maturation and declines thereafter, suggesting that the progressive reduction in DHEAS may play a role in the aging process and in the development of age-related morbidity. The present study examines changes in DHEAS concentrations across the life span of rhesus monkeys as part of the development of this primate model for studies of aging. Serum concentrations of DHEAS were measured in 792 laboratory-housed rhesus monkeys (Macaca mulatta) aged 0.5-36 years (527 females, 265 males). DHEAS concentrations in all monkeys were used to formulate an equation that describes two levels of decline of DHEAS with age. The most rapid decline occurs from infancy until approximately 5 years of age. The decline then occurs gradually with increasing age. There were no signs of an andrenarche just prior to sexual maturation, as is seen in humans or the great apes. This equation can be used to predict the expected mean serum DHEAS concentration and normal ranges of male or female rhesus monkeys at any age greater than 5 months.

Serum dehydroepiandrosterone sulfate concentrations in men with erectile dysfunction

Objectives. In 1994, the Massachusetts Male Aging Study presented the finding of an inverse correlation of the serum levels of dehydroepiandrosterone sulfate (DHEAS) and the incidence of erectile dysfunction (ED). Prompted by the positive results of a pilot study on the treatment of ED with dehydroepiandrosterone (DHEA), we performed a detailed investigation on the serum DHEAS levels in men with ED according to age category. Methods. Inclusion criteria included a history of ED for more than 6 months, a body mass index less than 30, and a state of good general health. Serum DHEAS concentrations were determined in 309 patients with ED and 133 healthy volunteers. All participants were carefully screened to assess medical factors known or suspected to alter endocrine function. Questions 3 and 4 of the International Index of Erectile Function were used to evaluate erectile function. Results. The mean serum levels of DHEAS in patients with ED were lower than in healthy volunteers until 60 years of age. The shape of the curve of the patients with ED indicated a quadratic decrease of DHEAS with age in contrast to a more linear decrease of DHEAS with age in the control group. Conclusions. Our results suggest that until the age of 60 years, the mean serum level of DHEAS is lower in patients with ED than in healthy volunteers.

Serum Dehydroepiandrosterone, Dehydroepiandrosterone Sulfate, and Pregnenolone Sulfate Concentrations in Patients with Hyperthyroidism and Hypothyroidism

Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) have been suggested to have protective effects against cardiovascular disease, cancer, immune-modulated diseases, and aging. We examined serum concentrations of DHEA, DHEA-S, and pregnenolone sulfate (PREG-S) in patients with thyroid dysfunction. Steroids extracted with methanol from serum sample were separated into an unconjugated fraction (DHEA) and a monosulfate fraction (DHEA-S and PREG-S), using a solid-phase extraction and an ion-exchange column. After separation of unconjugated steroids by HPLC, the DHEA concentration was measured by enzyme immunoassay. The monosulfate fraction was treated with arylsulfatase, and the freed steroids were separated by HPLC. The DHEA and PREG fractions were determined by gas chromatography-mass spectrometry, and the concentrations were converted into those of DHEA-S and PREG-S. Serum concentrations of DHEA, DHEA-S, and PREG-S were all significantly lower in patients with hypothyroidism (n = 24) than in age- and sex-matched healthy controls (n = 43). By contrast, in patients with hyperthyroidism (n = 22), serum DHEA-S and PREG-S concentrations were significantly higher, but the serum DHEA concentration was within the reference interval. Serum concentrations of these three steroids correlated with serum concentrations of thyroid hormones in these patients. Serum albumin and sex hormone-binding globulin concentrations were not related to these changes in the concentration of steroids. Serum concentrations of DHEA, DHEA-S, and PREG-S were decreased in hypothyroidism, whereas serum DHEA-S and PREG-S concentrations were increased but DHEA was normal in hyperthyroidism. Thyroid hormone may stimulate the synthesis of these steroids, and DHEA sulfotransferase might be increased in hyperthyroidism.

Exaggerated Adrenarche and Hyperinsulinism in Adolescent Girls Born Small for Gestational Age

Serum dehydroepiandrosterone-sulfate (DHEAS) is a classic marker for adrenarche and, subsequently, for the individual hormonal milieu. We have tested the hypothesis that prenatal growth reduction is followed by exaggerated adrenarche. Serum DHEAS, androstenedione and insulin concentrations were determined together with fasting glycemia in matched populations of asymptomatic, non-obese, post-menarcheal girls (mean age 14 yr) who were born either with a strictly appropriate weight for gestational age (AGA) or small for gestational age (SGA). When compared to AGA girls, the SGA girls had identical glucose levels, higher values for insulin and androstenedione (p<0.01), and a two-fold rise of DHEAS concentrations (p<0.0001). In conclusion, girls with prenatal growth reduction were found to be prone to develop, besides hyperinsulinism, a variant of exaggerated adrenarche. It remains to be verified whether the exaggerated adrenarche in adolescence is followed by adrenal hyperandrogenism throughout adulthood and senescence.

Biochemical mechanisms responsible for the attenuation of diabetic and obese conditions in ob/ob mice treated with dopaminergic agonists.

We previously reported that a two week treatment with SKF 38393 (SKF, a dopamine D1 receptor agonist), plus bromocriptine (BC, a dopamine D2 receptor agonist) acted synergistically to normalize hyperphagia, body fat, hyperglycaemia and hyperlipidaemia in ob/ob mice. The present study further investigates the biochemical mechanisms triggered by this drug treatment. Six week old female C57BL/6J ob/ob mice were divided into three groups and treated for two weeks with either BC and SKF, vehicle (control), or vehicle and pair fed to match the drug-treated group's daily food intake. BC/SKF treatment reduced food consumption by 55%, and treated mice weighed less than either pair fed or ad libitum fed controls after two weeks of treatment. Moreover, oxygen consumption was increased by 2.4-fold and the respiratory quotient (RQ) decreased from 1.23 to 0.96 (indicating a reduction in de novo lipogenesis) by drug treatment relative to ad libitum fed controls, but these parameters were unaffected by pair feeding control mice. The treatment also reduced blood glucose and free fatty acids (FFA) relative to pair fed and ad libitum fed controls. BC/SKF treatment (but not pair feeding) concurrently reduced lipolysis, lipogenic enzyme activities and hepatic gluconeogenic enzyme activities. Treatment also increased hepatic concentrations of glycogen and xylulose-5-phosphate (X-5-P), a key stimulator of glycolysis. Finally, BC/SKF, but not pair feeding, reduced the circulating concentrations of thyroxine and corticosterone, two hormones known to increase lipolysis, lipogenesis and hyperglycaemia. Drug treatment also increased serum dehydroepiandrosterone (DHEA) sulfate concentrations, an inhibitor of body fat store accumulation. These findings demonstrate that BC/SKF treatment not only normalizes hyperphagia of ob/ob mice, but also redirects several metabolic and endocrine activities, independent of its effects on feeding to improve the obese-diabetic syndrome in ob/ob mice.

Serum dehydroepiandrosterone sulfate concentration and thyroid cancer risk: a matched case control study.

In animal models of carcinogenesis, pharmacological doses of dehydroepiandrosterone (DHEA) treatment appear to reduce the incidence of chemically induced thyroid cancers. DHEA and its sulfate (DHEA-S) are secreted in approximately equal amounts, but serum levels of DHEA-S are 300-500 times higher and have no diurnal variation when compared to DHEA. The hypothesis that serum concentrations of DHEA-S may be associated with thyroid cancer risk was tested in a population-based prospective case control study. Data from the practically complete nationwide Cancer Registry of Norway were linked to the data file of a serum bank comprising blood samples from 300,000 Norwegian men and women obtained through national health surveys. A total of 113 donors, who during the years after blood sampling received a diagnosis of thyroid cancer, were identified in the serum bank and were eligible for the study. Each case was matched with 3 controls. Serum levels of DHEA-S were determined blindly. Controls were divided into tertiles, and odds ratios between cases and controls were determined relative to the group with the lowest serum DHEA-S level. The risk of developing thyroid cancer was determined in women 50 years of age or older, in women below age 50, in men, and in the subgroup of 77 cases who had morphologically verified papillary thyroid cancer. No significant association between prediagnostic serum DHEA-S concentrations and thyroid cancer risk was observed. These data indicate that DHEA-S within physiological concentrations does not reduce the risk of thyroid cancer.

Adrenal steroid hormones in short children born small for gestational age.

Programming of the endocrine axis has been postulated to occur during critical phases of fetal development and is affected by intrauterine growth retardation. The aim of this study was to investigate this hypothesis with regard to adrenal steroid hormones. Thus, serum cortisol and dehydroepiandrosterone sulphate (DHEAS) levels were compared in children born small for gestational age (SGA) who remained short and in children born at an appropriate size for gestational age (AGA), of both short and normal stature. Seven serum samples for cortisol measurements were taken during a 24-h period from a total of 184 prepubertal individuals. The study group comprised 53 children born SGA who remained short (41 boys, 12 girls; mean chronological age, 8.8 +/- 2.5 years). The reference groups of children born AGA were as follows: 75 healthy short children (56 boys, 19 girls; mean chronological age, 10.8 +/- 2.6 years) and 56 healthy children of normal height (37 boys, 19 girls; mean chronological age, 11.3 +/- 1.8 years). A single serum sample for measurement of DHEAS was taken between 1000 and 1400 h in 110 of the 184 children (33 short SGA, 42 short AGA and 35 AGA of normal height). Serum cortisol and DHEAS were measured by radioimmunoassay. No differences were found between children born SGA and children born AGA in either cortisol levels, calculated as area under the curve (AUC), or the circadian cortisol rhythm, estimated from the calculated nadir, the peak and the amplitude. No difference between the groups was found for serum DHEAS concentrations. Serum cortisol levels, expressed as AUC, and serum DHEAS levels did not correlate with size at birth. However, when adjusted for age at investigation, serum DHEAS, but not serum cortisol, correlated with weight at birth. Serum cortisol levels and rhythms do not correlate with size at birth and are similar in children born small for gestational age who remain short and children born appropriate size for gestational age of both short and normal stature. However, DHEAS levels in young children before adrenarche correlated inversely with weight at birth, indicating a relationship with fetal growth.

Effects of Molybdate and Pentachlorophenol on the Sulfation of Dehydroepiandrosterone

Pentachlorophenol (PCP) and molybdate have been shown to inhibit the sulfoconjugation of various chemicals in rats and therefore are useful to examine the role of sulfoconjugation on the toxicity of a chemical. PCP inhibits sulfation by competing with substrates for phenol–sulfotransferases, but not hydroxysteroid–sulfotransferases. In contrast, molybdate decreases sulfation by limiting sulfate availability and thereby decreasing the synthesis of 3′-phosphoadenosine 5′-phosphosulfate (PAPS), which is the obligate cosubstrate for sulfation. Therefore, it was of interest to determine whether PCP or molybdate is effective in decreasing thein vivosulfation of dehydroepiandrosterone (DHEA), which is a substrate for hydroxysteroid–sulfotransferases. PCP (40 μmol/kg ip) or molybdate (7.5 mmol/kg po) was given 45 min and 4 h, respectively, prior to the start of DHEA infusion. The effects of these two sulfation inhibitors on DHEA sulfation were dependent on the rate of DHEA infusion in rats. PCP had different effects on the sulfation of various infusion rates of DHEA in rats. PCP had little effect on the sulfation after the two lowest infusion rates of DHEA (12.5 and 25 mg/kg) and actually increased (233%) DHEA–sulfate serum concentrations with the highest DHEA infusion rate (50 mg/kg). Although molybdate had little affect on the sulfation of the lowest DHEA infusion rate, it significantly decreased (50–85%) DHEA–sulfate serum concentrations with the two higher DHEA infusion rates. These data indicate that molybdate, unlike PCP, decreases the sulfation of DHEA and may be a useful tool to decrease the sulfation of other substrates of hydroxysteroid–sulfotransferases.

Dehydroepiandrosterone sulfate does not prevent spontaneous and iodine-induced lymphocytic thyroiditis and diabetes mellitus in the BB/Wor rat.

Chronic feeding of dehydroepiandrosterone (DHEA) and its sulfated metabolite, dehydroepiandrosterone sulfate (DHEAS), has previously been reported to decrease hyperglycemia, obesity, cancer, and autoantibody generation in a number of animal models and to increase muscle mass and physiological and psychological well-being in elderly humans, although these latter studies remain controversial. The present study was carried out to determine whether large amounts of DHEAS given orally would prevent the occurrence of spontaneous and iodine-induced autoimmune lymphocytic thyroiditis (LT) and/or spontaneous insulin-dependent diabetes mellitus (DM) in male and female BB/Wor rats. DHEAS was administered by gavage (44 mg/rat/day) or in the chow (133 mg/rat/day) to LT- and DM-prone rats from 30 to 120 days of life; some of these rats also received iodine in the drinking water to enhance the incidence and intensity of LT. Onset of DM requiring protamine zinc insulin and its maintenance dose were assessed. Rats were killed at 90 or 120 days of age and blood, thyroid, adrenals, pancreases, testes, and ovaries were removed. Serum glucose, DHEA, DHEAS, thyroxine (T4), tri-iodothyronine (T3) and thyrotropin (TSH) concentrations were measured in all rats in both experiments. Serum DHEAS concentrations were 10-fold higher in the rats given the steroid by gavage or in the diet compared with levels in control rats. DHEAS administered over a prolonged period of time had no significant effect on body weight, incidence and severity of DM, incidence and intensity of spontaneous and iodine-induced LT, and thyroid, pancreas and testes weights but did significantly decrease adrenal and ovarian weights. Serum T4, T3, and TSH concentrations were similar in control and DHEAS-treated rats. In conclusion, DHEAS did not prevent the occurrence of iodine-induced or spontaneous autoimmune LT or spontaneous DM in the BB/Wor rat, at variance with its reported immunosuppressive effects in other animal models.

Fasting suppresses pulsatile luteinizing hormone (LH) secretion and enhances orderliness of LH release in young but not older men.

Pulsatile gonadotropin secretion and sex-steroid concentrations are suppressed reversibly in young fasted or malnourished human subjects. In this study, we investigated the impact of age on the dynamic neuroendocrine mechanisms underlying this stress response in healthy young (age, 28 +/- 3 yr, n = 8) vs. older (age 67 +/- 2 yr, n = 8) men with similar body mass indices (mean, 26 +/- 0.6 vs. 26 +/- 1.3 kg/m2, respectively). Serum LH concentrations were measured by immunoradiometric assay (IRMA) in blood collected at 10-min intervals over 27 h on a control (fed) day and on the third day of a 3.5-day fast (water only) assigned in randomized order. After 24 h of basal sampling, GnRH (10 micrograms i.v. bolus) was administered to test gonadotrope responsiveness. Cortisol, dehydroepiandrosterone sulfate, androstenedione, testosterone, FSH, GH, and PRL were measured in 24-h pooled serum as positive and negative control hormones. Approximate entropy was used to quantitate the orderliness of LH release over 24 h, and a multiple-parameter deconvolution method was applied to quantify pulsatile LH secretion and LH half-life. In the fed state, older men exhibited elevated mean (24-h pooled) serum FSH and cortisol concentrations compared with young controls but equivalent serum LH concentrations and reduced serum GH, free testosterone, androstenedione, and dehydroepiandrosterone sulfate concentrations. Fed older men also manifested a lower frequency and amplitude of 24-h pulsatile LH secretion, and, by approximate entropy calculations, a more disorderly pattern of basal LH release than younger individuals. Three- and one-half days of fasting evoked 40% and 47% increases in mean (24-h) serum cortisol concentrations in young and older men, respectively (P < 0.01 vs. fed, but P = not significant for percentage rise in older vs. young men). Concurrently, fasting induced a 2.1-fold fall in the 24-h endogenous LH production rate in young men (fed 36 +/- 9.7 vs. fasted 17 +/- 2.0 IU/L of distribution volume/day, P < 0.01), but did not significantly affect the daily LH secretion rate in older men (fed 27 +/- 4.5 vs. fasted 21 +/- 3.4 IU/day). The reduced LH production rate in fasting young men was accounted for by a 1.7-fold decline in the mass of LH secreted per burst (fed 2.5 +/- 0.45 vs. fasted 1.5 +/- 0.16 IU/L, P < 0.05), whereas LH burst mass in older men remained unchanged (and low) during fasting. In addition, in young men, during the 3.5-day fast the number of computer-resolved LH secretory bursts per 24 h decreased (fed 15 +/- 0.7 vs. fasted 11 +/- 0.7, P < 0.01), and the interburst interval increased (fed 94 +/- 4.2 vs. fasted 125 +/- 8.7 min, P < 0.05). In contrast, in older men in the fed state, basal LH peak frequency and serum free testosterone concentrations were reduced compared with corresponding values in young men, and did not decline further with fasting. Whereas the orderliness of LH release patterns increased significantly during fasting in the young men, the approximate entropy measure failed to change significantly in unfed older subjects. By cosinor analysis, young men showed lower 24-h mesor (mean of nyctohemeral rhythm of) serum LH concentrations than older volunteers during fasting. Moreover, young but not older men manifested preserved 24-h variations in LH interpulse intervals when fasting. Exogenously stimulated LH release (mean 3-h serum LH concentration or calculated mass of LH secreted) following a single i.v. injection of 10 micrograms GnRH was independent of age and fasting status. We conclude that the metabolic stressor of short-term fasting unmasks specific age-related neuroendocrine contrasts in the stress-responsive control of both the pulsatile and nyctohemeral regulation of the male hypothalamo-pituitary-gonadal-axis.