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At least 19 recordsLinked to original sources
PubMed2001

Dehydroepiandrosterone supplementation in healthy men with an age-related decline of dehydroepiandrosterone secretion.

Serum dehydroepiandrosterone declines with age. Whether this represents a harmful deficiency or an age-related adaptation is not known. Dehydroepiandrosterone replacement in adrenal insufficiency, a state of pathological loss of dehydroepiandrosterone production, improves well-being, mood, and sexuality. To determine the effects of dehydroepiandrosterone in healthy men with a physiological, age-related decline in serum dehydroepiandrosterone sulfate, we conducted a double blind cross-over study in 22 healthy male volunteers (age range, 50-69 yr) with endogenous dehydroepiandrosterone sulfate levels below 4.1 micromol/liter (1500 ng/ml) receiving 4 months of dehydroepiandrosterone (50 mg/d) and 4 months of placebo treatment in random order, with a 1-month washout period. Dehydroepiandrosterone treatment increased serum dehydroepiandrosterone and dehydroepiandrosterone sulfate to concentrations usually found in young men. Circulating androgen levels did not change; however, androgen metabolites increased, indicating enhanced peripheral androgen synthesis. At baseline, psychometric assessment revealed normal well-being and sexuality scores. After 4 months of dehydroepiandrosterone, no effect on sexuality was observed, whereas some mood scores improved slightly, but were not significantly different from scores after placebo. Compared with placebo, dehydroepiandrosterone had no effect on serum lipids, bone markers, body composition, or exercise capacity. Thus, in contrast to previous findings in adrenal insufficiency, we found no obvious benefit of 4 months of dehydroepiandrosterone supplementation in healthy men with a physiological decline of dehydroepiandrosterone production.

Affect↗
PubMed2003

Adrenocortical hormones in survivors and nonsurvivors of severe sepsis: diverse time course of dehydroepiandrosterone, dehydroepiandrosterone-sulfate, and cortisol.

OBJECTIVE: Activation and suppression of immune responses are crucial events during sepsis. Based on substantial new data, a complex picture of differential immune-enhancing and immunosuppressive actions of adrenocortical steroids is emerging. The adrenal androgen dehydroepiandrosterone and its precursor, dehydroepiandrosterone-sulfate, show a considerable decrease with increasing age and serve as functional antagonists to endogenous glucocorticoids. Therefore, we examined time-dependent changes in dehydroepiandrosterone, dehydroepiandrosterone-sulfate, cortisol, adrenocorticotropin, and inflammatory variables in surviving and nonsurviving patients with severe sepsis. DESIGN: Prospective observational study in consecutive patients. SETTING: Medical and interdisciplinary intensive care units in two university hospitals and one city hospital. PATIENTS: Thirty nonsurgical patients (25 men and 5 women) with severe sepsis (American College of Chest Physicians/Society of Critical Care Medicine criteria); 15 survivors (mean age, 54 +/- 14 yrs; Acute Physiology and Chronic Health Evaluation III score, 59 +/- 35) and 15 nonsurvivors (mean age, 63 +/- 15 yrs; Acute Physiology and Chronic Health Evaluation III score, 67 +/- 24) were included. Hormones were compared individually and between survivors/nonsurvivors by sequential blood drawings from early sepsis till time of recovery/death. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: During early sepsis, cortisol (nmol/L) was not significantly higher in survivors than nonsurvivors (750 +/- 121 vs. 454 +/- 92, p <.08) and decreased in survivors (p <.01) during late sepsis. During early sepsis, dehydroepiandrosterone-sulfate (percentage of age-matched normal levels) was higher in survivors than nonsurvivors (85 +/- 19 vs. 22 +/- 7, p <.01). Dehydroepiandrosterone-sulfate decreased in survivors (p =.0001) but remained low in nonsurvivors during late sepsis. Dehydroepiandrosterone (percentage of age-matched normal levels) was not significantly elevated in survivors compared to nonsurvivors during early sepsis (282 +/- 42 vs. 214 +/- 63, p <.08). Dehydroepiandrosterone decreased in survivors (p <.01) but not in nonsurvivors during late sepsis. Linear regression for dehydroepiandrosterone levels showed a reconstitution of age dependence only in survivors during recovery. Adrenocorticotropin levels did not change. The dehydroepiandrosterone-sulfate/cortisol ratio decreased significantly in both survivors and nonsurvivors, whereas dehydroepiandrosterone/cortisol ratio only decreased in survivors during course of sepsis. CONCLUSIONS: During sepsis, adrenal androgens and glucocorticoids show a diverse time-dependent course in survivors and nonsurvivors.

APACHE↗
PubMed1992

Relationship of prediagnostic serum levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate to the risk of developing premenopausal breast cancer.

Dehydroepiandrosterone and dehydroepiandrosterone sulfate are steroids which may be associated with the development of breast cancer. To examine the association between serum levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate and the risk of developing premenopausal breast cancer, we measured hormone levels in 15 women who donated blood to a community-based serum bank in 1974 and who subsequently developed premenopausal breast cancer and in 29 matched controls from the same group of volunteers. The mean serum level of dehydroepiandrosterone among cases was 10% lower than among controls. The risk of developing breast cancer for women in the highest tertile compared with the lowest tertile of serum dehydroepiandrosterone was 0.40 with a suggestion of a dose-response trend with increasing levels. No consistent association between dehydroepiandrosterone sulfate and the risk of premenopausal breast cancer was evident. In contrast to postmenopausal breast cancer, a protective effect of dehydroepiandrosterone against premenopausal breast cancer is suggested, but because of the small sample size, the results of this study need to be replicated by others.

Adolescent↗
PubMed1993

Role of dehydroepiandrosterone and dehydroepiandrosterone sulfate for the maintenance of axillary hair in women.

To delineate the relationship between sex hormones and the axillary hair in women, serum concentrations of dehydroepiandrosterone, dehydroepiandrosterone sulfate and testosterone were measured in 177 normal women (aged 16 to 76 y). Both menstrual cycle and axillary hair were present in all normal women younger than 50 years. In the 6th decade, axillary hair was present in 21 of 42 normal women but menstruation was present only in 8 of the 42 women. In the 7th and 8th decades, axillary hair was present in 36% and 25% of them, respectively. None of the subjects over 60 years of age had a menstrual cycle. Serum dehydroepiandrosterone and dehydroepiandrosterone-sulfate concentrations were significantly higher in axillary hair-positive than in -negative women after 50 years of age. Serum testosterone concentration was low in normal women after 50 years of age compared to those of under 49 years, and it was marginally lower in axillary hair-negative than in -positive normal women. However the difference between the axillary hair-positive and -negative subjects was not statistically significant. It is suggested that weak adrenal androgens such as dehydroepiandrosterone and dehydroepiandrosterone-sulfate, rather than testosterone, play an important role for the maintenance of axillary hair in aged women.

Adolescent↗
PubMedDate not supplied

Serum levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate and the risk of developing gastric cancer.

Although the incidence of gastric cancer varies widely between countries it is nonetheless a leading cause of cancer deaths worldwide. Migration studies indicate that dietary choices are an important exogenous factor. The United States has a very low incidence of gastric cancer, suggesting that exogenous etiological agents are at a minimum and providing a favorable setting for detecting important endogenous etiological factors. Dehydroepiandrosterone and dehydroepiandrosterone sulfate are endogenous steroids produced in the adrenal gland. Epidemiological studies show that the risk of developing specific cancers is related to the serum or urinary levels of these steroids. In addition, dehydroepiandrosterone prevents a variety of spontaneous and chemically induced tumors when administered to laboratory animals. To examine the association between circulating levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate and the development of gastric cancer, we measured the serum levels of these steroids in 13 individuals who donated serum to the Washington County Maryland serum bank in 1974 and who subsequently developed gastric cancer and in 52 matched controls. Prediagnostic serum levels of dehydroepiandrosterone were 38% lower in cases as compared to controls (P = 0.09). The risk of developing gastric cancer increased with decreasing levels of both steroids. Adjustment for confounding factors such as smoking or the interval between blood donation and time to diagnosis did not alter the findings. These results suggest that there may be a role for this steroid in the prevention of gastric cancer.

Adolescent↗
PubMed1992

Administration of pregnenolone and dehydroepiandrosterone to guinea pigs and rats causes the accumulation of fatty acid esters of pregnenolone and dehydroepiandrosterone in plasma lipoproteins.

Steroids were administered continuously to guinea pigs and rats using subcutaneously applied silastic tubing implants, and the effects on circulating steroid and steroid conjugate levels were monitored. Using implants filled with pregnenolone, we observed that pregnenolone had a marked effect on increasing the levels of its fatty acid-esterified derivative, while dehydroepiandrosterone-releasing implants produced a rise in circulating nonconjugated dehydroepiandrosterone, androst-5-ene-3 beta,17 beta-diol, androstenedione, testosterone, and lipoidal derivatives of both dehydroepiandrosterone and androst-5-ene-3 beta,17 beta-diol. Implants filled with androstenedione produced a 20-fold increase in plasma androstenedione levels relative to untreated controls and a corresponding five-fold increase over control testosterone levels. No fatty acid-esterified derivative of testosterone could be detected within the plasma. Lipoproteins were isolated from both rats and guinea pigs treated with implants filled with pregnenolone or dehydroepiandrosterone. The steroid and steroid fatty acid esters present in each fraction were analyzed, revealing that approximately 75% of all the fatty acid esters of pregnenolone recovered in the lipoproteins was localized within the high-density lipoprotein (HDL) fraction of both guinea pig and rat plasma. Similarly, lipoidal dehydroepiandrosterone was found associated predominantly with the low-density lipoprotein and HDL fractions in the guinea pig, while in the rat this steroid conjugate was exclusively within the HDL fraction. High-density lipoprotein-incorporated tritiated pregnenolone fatty acid esters and dehydroepiandrosterone fatty acid esters were injected into castrated male guinea pigs to study the fate of these complexes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1976

Dynamic appearance of [4-14C] dehydroepiandrosterone and [7 alpha-3H] dehydroepiandrosterone sulphate metabolites in urine of normal and obese female subjects.

[4-14C]-Dehydroepiandrosterone and [7 alpha-3H]-Dehydroepiandrosterone sulphate were injected simultaneously to normal and obese female subjects. The percentage recovery of 14C and 3H radioactivies in dehydroepiandrosterone sulphate, androsterone sulphate, etiocholanolone sulphate, androsterone glucuronoside and etiocholanolone glucuronoside was determined in the day-to-day urine collections for 72 hr. Results showed a normal total 3H recovery and a poor 14C recovery in urinary conjugates of obese patients. The rate of appearance of 3H activity was not identical in the individual metabolites of normal subjects, and it was not normal in obesity. Overweight subjects exhibited an acceleration in [7 alpha-3H]-Dehydroepiandrosterone sulphate metabolism to androsterone glucuronoside. The observation regarding the rate of appearance of urinary conjugates bearing 14C isotope correlate with our previous finding in which a glandular overproduction of free dehydroepiandrosterone was found and an uptake of this steroid by the adipose tissue was suggested. Our results showed that the poor recovery of 14C radioactivity in urine of obese female subjects was not an aspecific consequence of illness.

Adult↗
PubMed2003

Clozapine decreases rat brain dehydroepiandrosterone and dehydroepiandrosterone sulfate levels.

We examined the influence of the atypical antipsychotic agent clozapine compared to haloperidol, on levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate ester (both gamma-aminobutyric acid(A) (GABA(A)) receptor allosteric antagonists) in the rat cortex. i.p. injections of clozapine (5 and 15 mg/kg), but not haloperidol (1 mg/kg), for 8 days decreased rat brain cortical dehydroepiandrosterone and dehydroepiandrosterone sulfate levels. These findings support the role of neurosteroids and possibly GABA(A) receptor modulation in the mechanism of action of clozapine.

Animals↗
PubMed1990

Relationship of serum levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate to the risk of developing postmenopausal breast cancer.

Dehydroepiandrosterone and dehydroepiandrosterone sulfate are endogenous steroids that are produced in the adrenal cortex. A number of studies have suggested that circulating levels of these hormones are related in some way to the risk of developing breast cancer. We measured serum levels of these steroids in 30 postmenopausal women who donated blood in 1974 for a community-based serum bank and who subsequently, at least 9 years later, developed breast cancer and in 59 matched controls from the same group of volunteers. Significantly elevated serum levels of dehydroepiandrosterone were found among cases prior to diagnosis compared to controls; serum levels of dehydroepiandrosterone sulfate were slightly increased among cases. In controls, current cigarette use was associated with increased serum levels of these steroids, and levels of both steroids decreased with age.

Aged↗
PubMed2005

Synthesis of 7alpha-hydroxy-dehydroepiandrosterone and 7beta-hydroxy-dehydroepiandrosterone.

The fermentation of dehydroepiandrosterone synthesized from the starting material diosgenin using Mucor racemosus produced 7alpha-hydroxy-dehydroepiandrosterone and 7beta-hydroxy-dehydroepiandrosterone. The bioactivity of the microbial metabolites is also discussed. The species M. racemosus was isolated by screening among stains from soil samples collected from various parts of China.

Dehydroepiandrosterone↗
PubMed1975

Synthesis of dehydroepiandrosterone and dehydroepiandrosterone sulphate by the human adrenal.

The role of pregnenolone sulphate in adrenal steroid biosynthesis and the ability of the human adrenal gland to synthesize and secrete dehydroepiandrosterone (DNA) and dehydroepiandrosterone sulphate (DHA sulphate) was investigated. The presence of pregnenolone sulphate and DHA sulphate was demonstrated by measuring their concentrations in human adrenal tissue. Pregnenolone sulphate was metabolized in vitro mainly to free steroids, including DHA and cortisol, as well as directly to DHA sulphate in some cases. Similar results were obtained upon perfusion of the adrenal gland in situ with [14C]pregnenolone and [13H]prenenolone sulphate as the substrates and isolating the metabolites from the adrenal venous blood. Dehydroepiandrosterone sulphate was derived mainly from the sulphation of free DHA. The hydrolysis of DHA sulphate did not appear to make a significant contribution to the amounts of DHA synthesized under these conditions. The adrenal secretion of DHA and DHA sulphate by eight patients undergoing adrenal-ectomy was determined by measuring the concentrations of these compounds in samples of adrenal and peripheral venous blood taken simultaneously. In one patient secretion of DHA and DHA sulphate was equivalent whilst in the remainder there was much greater secretion of DHA.

17-alpha-Hydroxypregnenolone↗
PubMed1988

Dehydroepiandrosterone sulphate and dehydroepiandrosterone in serum: differences related to age and sex.

Serum concentrations of dehydroepiandrosterone sulphate (DHAS) were determined in 590 healthy women aged 20-87 yr. Simultaneous assays of dehydroepiandrosterone (DHA) were performed in 417 of the women. DHA and DHAS levels correlated negatively with age while the DHA/DHAS ratio proved to be unrelated to age. When values for 60 healthy men in the age range 20-84 yr were compared with those obtained in 60 randomly-selected healthy women who were exactly age-matched, the DHAS levels were found to be significantly lower and the DHA/DHAS ratios significantly higher in the women. These results might be of use in establishing normal clinical ranges for serum DHA, DHAS and the DHA/DHAS ratio in women.

Adult↗
PubMed1995

Transport of dehydroepiandrosterone and dehydroepiandrosterone sulphate into rat hepatocytes.

The purpose of the present study was to characterize the transport of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) into hepatocytes at physiological and pharmacological concentrations. Hepatocytes were isolated from female Sprague-Dawley rats by collagenase perfusion. Uptake of [3H]DHEA and [3H]DHEAS at increasing concentrations (3.5 nM-100 microM) was measured by the rapid filtration technique at 30 s intervals up to 120 s. The uptake of DHEAS by hepatocytes was saturable (Km = 17.0 microM; Vmax = 3.7 nmol/min/mg cell protein). In contrast, a specific saturable transport system for DHEA could not be detected in rat hepatocytes. It is suggested that DHEA enters the cell by diffusion. The uptake of DHEAS could be inhibited by antimycin A, carbonylcyanide-m-chlorophenylhydrazone, and dinitrophenol (inhibitors of the mitochondrial respiratory chain), by dinitrofluorobenzene and p-hydroxymercuribenzoate (NH2- and SH-blockers, respectively), and by monensin (Na(+)-specific ionophore). No inhibition was seen in the presence of ouabain (inhibitor of Na(+)-K(+)-ATPase) and phalloidin (inhibitor of cholate transport and actin-blocker). Interestingly, DHEAS uptake was inhibited by bile acids (cholate, taurocholate and glycocholate). Conversely, [3H]cholate uptake was strongly inhibited by DHEAS, which indicates a competition for the same carrier. Replacement of sodium ion with choline markedly decreased uptake velocity at pharmacological DHEAS concentrations. The results suggest that DHEAS uptake is a saturable, energy-dependent, carrier-mediated, partially Na(+)-dependent process, and that DHEAS may be taken up via the multispecific bile acid transport system.

Animals↗
PubMed1996

Effects of joining peptide (1-18) and histamine on dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) production of human adrenocortical cells in vitro.

Joining peptide 1-18 (JP 1-18), added alone in concentrations of 10(-13)-10(-7) M to collagenase-dispersed human adrenocortical cells, did not affect the basal production of corticosterone, cortisol, aldosterone, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS). JP 1-18 potentiated the ACTH-stimulated production of steroids. When administered in combination with histamine (10(-8)-10(-3) M), JP 1-18 (10(-8) or 10(-10) M), enhanced the synthesis of DHEA and DHEAS. JP 1-18, together with histamine, may play a role in the regulation of DHEA and DHEAS production.

Adrenal Cortex↗
PubMed2004

Serum concentrations of dehydroepiandrosterone and dehydroepiandrosterone sulfate and their relation to cytokine production during and after normal pregnancy.

BACKGROUND: Since dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) have been suggested to have immunoregulatory effects, changes in the levels of these substances during and after pregnancy might affect the maternal immune system. We examined serum concentrations of DHEA and DHEAS, and cytokine production during pregnancy and after delivery. METHODS: The subjects were 73 normal pregnant, 76 normal postpartum and 30 normal non-pregnant women. Whole-blood was stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin and the levels of cytokines in the supernatant were measured using enzyme-linked immunosorbent assay (ELISA). DHEA and DHEAS were measured using ELISA and gas chromatography-mass spectrometry (GC-MS), respectively. RESULTS: The serum DHEA levels increased in the first and in the second trimesters and decreased after delivery until 11 months postpartum. DHEAS levels were decreased in the second and in the third trimesters and returned to non-pregnant levels after pregnancy. All measured cytokines (IFN-gamma, IL-2, IL-4 and IL-10) were decreased during pregnancy and subsequently increased postpartum. We found significant negative correlations between DHEA and cytokine levels. CONCLUSIONS: Increase of serum DHEA in the first and the second trimesters may suppress immune reaction during pregnancy, while a decrease of DHEA after delivery may induce postpartum enhancement of the maternal immune system. DHEA may be involved in modifying the maternal immune responses during and after pregnancy.

Adult↗
PubMed1999

Relation of dehydroepiandrosterone and dehydroepiandrosterone sulfate with cardiovascular disease risk factors in women: longitudinal results from the Massachusetts Women's Health Study.

Low circulating levels of the adrenal steroids dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) are thought to be associated with increased risk of cardiovascular disease (CVD) in men. In women, either a positive or null association with CVD has been found. The nature of the relation between DHEAS and CVD risk factors in women is unclear and is based on cross-sectional data. We present results from a longitudinal investigation of serum DHEA and DHEAS and cardiovascular disease risk factors in 236 women, initially 50-60 years old, from a population-based prospective (1986-1995) study of the menopausal transition. We used generalized estimating equations to model the relation of serum DHEA and DHEAS to systolic and diastolic blood pressure and serum levels of total cholesterol, high density lipoprotein cholesterol, and apolipoproteins A and B, adjusting for other factors related to CVD. Both DHEA and DHEAS were positively related to diastolic and systolic blood pressure, and DHEAS was negatively related to apolipoprotein A. DHEA and DHEAS were also positively related to smoking, alcohol use, estrone, and estradiol levels, and inversely related to age. Our results suggest that higher levels of DHEA and DHEAS in middle-aged women may indicate increased CVD risk.

Aged↗
PubMed1984

Plasma dehydroepiandrosterone, dehydroepiandrosterone sulphate and androsterone sulphate levels and their interaction with plasma proteins in rheumatoid arthritis.

Female patients with rheumatoid arthritis (RA) in Steinbrocker's II and III rating scale have been examined. They were without steroid treatment at least six months before observation. Plasma protein picture showed hypoalbuminaemia and hyperglobulinaemia. There was no difference relative to controls either in the total (free + protein bound) plasma dehydroepiandrosterone (D) level, or in its distribution with plasma proteins. In the age group of 18 to 45 years, a statistically significant decrease have been observed in the total plasma dehydroepiandrosterone sulphate (DS) level without any change in its distribution in protein binding. Furthermore, low androsterone sulphate (AS) levels were found irrespective of the age of patients. The results gave further information on the pathomechanism resulting in an abnormal androgen hormone pattern of blood and a low metabolite excretion, observed previously in patients with RA:.

Adolescent↗