PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “DHEAS”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 55 records · Page 3Linked to original sources
PubMed1992

Dehydroepiandrosterone (DHEA) and synthetic DHEA analogs are modest inhibitors of HIV-1 IIIB replication.

Down-regulation of Epstein-Barr virus (EBV) induced transformation of human lymphocytes in vitro by dehydroepiandrosterone (DHEA), a naturally occurring human steroid secreted by the adrenal gland has been demonstrated. This article reports on the effects of DHEA and its novel synthetic analogs 16 alpha-fluoro-5-androsten-17-one (8354) and 3 beta-hydroxy-16 alpha-fluoro-5 alpha-androstan-17-one (OH8356) on human immunodeficiency virus (HIV-1) replication. Treatment with DHEA, 8354, or OH8356 resulted in a modest down-regulation of HIV-1 replication in phytohemagglutinin-stimulated peripheral blood lymphocytes as measured by syncytia formation, release of p24 antigen, and accumulation of reverse transcriptase activity. DHEA and 8354 also reduced syncytia formation in HIV-1-infected SupT1 lymphoblasts. DHEA and synthetic analogs of DHEA, which have been shown previously to have antiproliferative effects, now are shown to reduce HIV-1 replication. DHEA or synthetic analogs of DHEA could provide an alternative and/or adjuvant for HIV-1 infection.

Androstenes↗
PubMed2005

Impact of gastric banding on plasma ghrelin, growth hormone, cortisol, DHEA and DHEA-S levels.

BACKGROUND: Several endocrine abnormalities are reported in obesity. Some are considered as causative factors, whereas others are considered to be secondary effects of obesity. In the current study, we explored the changes in cortisol, growth hormone (GH), DHEA, DHEA-S and GH releasing hormone (ghrelin) plasma levels in morbidly obese subjects who lost abundant weight following laparoscopic adjustable gastric banding (LAGB). METHODS: 12 morbidly obese adult patients (15 females), age 21-56 years with BMI 46.0+/-4.4 kg/cm(2), were studied. Blood samples were collected before, 6 and 14 months after LAGB. The levels of DHEA, DHEA-S, cortisol, GH, and ghrelin were determined by commercial kits. Statistical analysis was based on one-way repeated measures ANOVA, followed by Student-Newman-Keuls post-hoc test. RESULTS: Mean BMI reduced significantly along the study course (P=.000). Cortisol plasma levels significantly decreased 6 months after surgery (from 541.4+/-242.4 nM to 382.4+/-142.1 nM, P=.004), but did not change further after 14 months (460.2+/-244.9 nM), despite further reduction in BMI (P=.050). GH constantly increased throughout the study from 0.076+/-0.149 ng/ml, to 0.410+/-0.509 ng/ml at 6 months (NS), to 1.224+/-1.738 ng/ml at 14 months after surgery (P=.001). DHEA, DHEA-S and ghrelin plasma levels remained stable throughout the study. CONCLUSIONS: GH levels showed a persistent increase during the 14 months following LAGB in association with the weight loss, while a transient decrease in cortisol levels occurred at the 6-months time-point. In contrast, ghrelin, DHEA and DHEA-S were not altered after surgery. The association between GH and cortisol secretion and surgical- and nonsurgical-induced weight reduction merits further investigation.

Adult↗
PubMed1988

Dehydroepiandrosterone sulfate (DHEA-S) and DHEA-S-like compounds in fibrocystic disease of the breast.

We assayed Type 1 (high K+) and Type 2 (high Na+) human breast cyst fluids for DHEA-S. When an antibody specific for the 3-sulfoconjugate end of DHEA-S was used, Type 1 cyst fluids (n = 18) showed a content of 114 +/- 68 micrograms/mL (mean +/- sigma) and Type 2 cyst fluids (n = 14) of 35 +/- 17 micrograms/mL (P less than 0.01). Using an antibody specific for the D-ring, the results were 151 +/- 91 micrograms/mL and 51 +/- 32 micrograms/mL, respectively (P less than 0.01). The apparent concentrations of DHEA-S were statistically different, even though both assays gave equal results in serum from normal adults. The presence of other compounds in individual cyst fluid samples was examined by extraction and chromatography. DHEA-S immunoreactivity was found in both early and late eluting fractions in Type 1 cyst fluids and in late eluting fractions from Type 2 cyst fluids. Only the late eluting fraction from Type 2 fluids had approximately equal immunoreactivity with both antibodies. In addition to authentic DHEA-S, breast cyst fluids contain other materials that react with DHEA-S antibodies. Radioimmunoassays for DHEA-S in cyst fluid must be specifically validated because of the presence of these compounds.

Body Fluids↗
PubMed2000

Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue.

The secretion and the blood levels of the adrenal steroid dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) decrease profoundly with age, and the question is posed whether administration of the steroid to compensate for the decline counteracts defects associated with aging. The commercial availability of DHEA outside the regular pharmaceutical-medical network in the United States creates a real public health problem that may be resolved only by appropriate long-term clinical trials in elderly men and women. Two hundred and eighty healthy individuals (women and men 60-79 years old) were given DHEA, 50 mg, or placebo, orally, daily for a year in a double-blind, placebo-controlled study. No potentially harmful accumulation of DHEAS and active steroids was recorded. Besides the reestablishment of a "young" concentration of DHEAS, a small increase of testosterone and estradiol was noted, particularly in women, and may be involved in the significantly demonstrated physiological-clinical manifestations here reported. Bone turnover improved selectively in women >70 years old, as assessed by the dual-energy x-ray absorptiometry (DEXA) technique and the decrease of osteoclastic activity. A significant increase in most libido parameters was also found in these older women. Improvement of the skin status was observed, particularly in women, in terms of hydration, epidermal thickness, sebum production, and pigmentation. A number of biological indices confirmed the lack of harmful consequences of this 50 mg/day DHEA administration over one year, also indicating that this kind of replacement therapy normalized some effects of aging, but does not create "supermen/women" (doping).

Absorptiometry, Photon↗
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↗
PubMed1998

Dehydroepiandrosterone (DHEA) and DHEA-S interact with 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) to stimulate human osteoblastic cell differentiation.

DHEA, an adrenocortical steroid, and its sulfate derivative (DHEA-S), have been implicated in many biological functions, including the regulation of bone mass. In this study, we examined whether DHEA/DHEA-S are capable of directly affecting bone cell proliferation and differentiation, and compared this with the effects of, and interaction with, the established bone cell modulating steroid, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). Two in vitro models of human osteoblastic cells were used, viz. MG63 osteosarcoma cell line and normal primary osteoblast-like cells (HOB). Our results show that DHEA and DHEA-S failed on their own to exert direct, independent significant effects on the growth and differentiation of human osteoblastic cells, but treating the cells in conjunction with 1,25(OH)2D3 resulted in enhancement of specific A1P activity. Moreover, 1,25(OH)2D3-induced osteocalcin production was potentiated by the adrenal steroids in both cell models. DHEA-S proved in general to be more potent than DHEA. In conclusion, this study shows that the effects of DHEA/DHEA-S on osteoblastic cell growth and differentiation are likely to be mediated via an effect on 1,25(OH)2D3-induced changes in bone cells, suggesting a distinctive role for these steroids in the regulation of bone metabolism.

Calcitriol↗
PubMed2000

Conversion of pregnenolone to DHEA by human 17alpha-hydroxylase/17, 20-lyase (P450c17). Evidence that DHEA is produced from the released intermediate, 17alpha-hydroxypregnenolone.

Most previous studies using reconstituted systems and fast kinetics suggest that the conversion of pregnenolone to dehydroepiandrosterone (DHEA; the precursor of androgen and estrogen biosynthesis) by P450c17 does not require the release of the intermediate 17alpha-OHPreg (a precursor of cortisol biosynthesis). With such a mechanism, it is difficult to conceive how high amounts of DHEA may be produced in some cells or tissues, such as the testis and cells from the adrenal reticularis, while in other tissues such as the fasciculata zone, high levels of 17alpha-OHPreg are synthesized. In this report, we address this matter using intact transfected cells, which better reflect the actual cellular conditions. Furthermore, by using transfected cells, we can conveniently analyze human enzymes, as we are not restricted by the availability of human tissues as in the case of methods using purified or partially purified enzymes. Using intact HEK-293 cells transfected with human P450c17 in culture, we showed, in a time course study of the transformation of pregnenolone, that there is an accumulation of 17alpha-OHPreg, and that, subsequently, the accumulated 17alpha-OHPreg decreases with a concomitant increase in DHEA production. The DHEA/17alpha-OHPreg ratio changes from 0.1 :1 after 1 h incubation to 50 : 1 after 20 h. This result strongly suggests that the transformation of Preg to DHEA proceeds through two steps in which DHEA is produced from the released intermediate 17alpha-OHPreg. We also show that high levels of substrate vs. enzyme concentration will lead to high hydroxylase activity whereas the reverse will increase the lyase activity. The result is in good agreement with recent observations suggesting that surrounding enzymes and steroids could modulate the lyase activity. Cotransfection of vectors expressing cytochrome b5 and NADPH cytochrome P450 reductase indicates that both are required for an optimum production of DHEA.

17-alpha-Hydroxypregnenolone↗
PubMed1998

Dehydroepiandrosterone (DHEA) and DHEA-sulfate (DS) as therapeutic options in menopause.

In recent years, there has been increasing interest in the potential of androgen replacement in menopausal women and specifically adrenal androgen replacement. There is unfortunately increasing unmonitored use of dehydroepiandrosterone (DHEA) among adults in the United States with only limited and preliminary human data. An extensive body of literature in laboratory animals exists to suggest DHEA used in extremely large doses has multifaceted effects; though the inapplicability of this data to humans is not appreciated, as the physiology of adrenal androgens in humans and a few primates is unique. Currently, there is much international and multidisciplinary interest in the physiology and use of DHEA "replacement" in men and menopausal women. The scientific community anxiously await the results of these investigations, but in the interim DHEA and/or DHEA-Sulfate (DHEAS) supplementation is not recommended as a therapeutic option in menopause outside of clinical trials.

Adult↗
PubMed1985

Discordance of plasma DHEA-S, DHEA, and cortisol responses with various ACTH regimens.

The origin and time course of ACTH-stimulated adrenal androgens are controversial. Since previous protocols have used differing ACTH preparations and routes of administration, we sought to compare plasma DHEA and DHEA-S responses to four ACTH regimens. Fourteen young men underwent the following five three-day study periods: (1) placebo, (2) alpha 1-24 ACTH, 400 micrograms intravenously (IV); (3) alpha 1-39 ACTH, 400 micrograms intramuscularly (IM); (4) alpha 1-18 (D-Ser1, Lys17, Lys18) ACTH, 400 micrograms IM; and (5) alpha 1-18 ACTH, 400 micrograms IV. alpha 1-18 ACTH IV had the most potent and prolonged corticotropic effect, listing more than 24 hours, as measured by plasma cortisol, 17-OHCS, and cortisol secretion rates. alpha 1-39 ACTH and alpha 1-18 ACTH IM were corticotropic up to 12 hours, and alpha 1-24 ACTH IV was corticotropic only up to one hour. Plasma DHEA rose acutely at one hour with all of the ACTH regimens (P less than 0.05). This response was correlated with cortisol (r = 0.62, P less than 0.01) and reflected the relative corticotropic potency of each of the ACTH regimens. Plasma DHEA-S, on the other hand, did not rise acutely at one hour with any of the regimens. DHEA-S did rise at 12 hours with three of the ACTH regimens (alpha-1-24, alpha 1-39, alpha 1-18 IM), but this response was not synchronous with cortisol (r = 0.14, P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗
PubMed2005

The involvement of dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) in blocking the therapeutic effect of electroconvulsive shocks in an animal model of depression.

Depressed patients with resistance to electroconvulsive treatment (ECT) had high basal serum levels of dehydroepiandrosterone (DHEA) sulfate (DHEAS). To clarify the role of DHEA/S in the ECT resistance, Flinder Sensitive Line (FSL) rats, which are a genetic animal model of depression, were injected i.p. with 2 mg/kg DHEA daily for 13 days to overload their serum and brain DHEA/S levels. Thereafter, rats were exposed to electroconvulsive shock (ECS), which is analogue to ECT in humans. Both ECS and DHEA displayed an antidepressive-like effect, as assessed by immobility time in forced swim test. However, combined DHEA and ECS treatment abolished these antidepressive-like effects. In addition, the levels of neurosteroids, corticosterone and adrenocorticotropin in selected brain regions were evaluated and compared to serum levels. The present study supports our assumption that high basal levels of DHEA/S play a role in the resistance to ECS and maybe ECT in humans.

Adrenocorticotropic Hormone↗
PubMed2005

Dehydroepiandrosterone (DHEA) metabolism in the brain: identification by liquid chromatography/mass spectrometry of the delta-4-isomer of DHEA and related steroids formed from androstenedione by mouse BV2 microglia.

Studies to elucidate the role of dehydroepiandrosterone (DHEA) metabolism in neuroprotection have compared its relative 7-hydroxylation against estrogen formation by way of 4-androstenedione (AD) in various rodent brain cell lines. In all cases, the 7alpha- and 7beta-hydroxy epimers of DHEA were found to be the dominant products with one notable exception. BV2 mouse microglia were virtually unable to hydroxylate DHEA at C-7 and converted AD to a major unknown metabolite not observed with mouse BHc hippocampal cells. In this paper, we describe the identification of this compound based on its physical properties and analysis by TLC and HPLC. Its identity as 3beta-hydroxy-4-androstene-17-one, the Delta(4)-isomer of DHEA, was confirmed by mass spectrometry (LC/MS), as well as by reverse isotope dilution analysis involving co-crystallization with the synthetic steroid. Possible mechanisms for the formation of this isomer of DHEA by BV2 microglia are proposed, together with that of other C-19 steroids detected which include testosterone (T), 5alpha-dihydrotestosterone and 5alpha-androstanedione.

Adjuvants, Immunologic↗
PubMed2005

Beneficial effects and side effects of DHEA: true anti-aging and age-promoting effects, as well as anti-cancer and cancer-promoting effects of DHEA evaluated from the effects on the normal and cancer cell telomeres and other parameters.

The author evaluated the effects of DHEA (Dehydroepiandrosterone) on the amount of telomeres of normal cells and cancer cells and found the following: Contrary to the literature, which often recommended 25-50 mg of DHEA daily for the average adult human being, the author found that, depending on the individual, the maximum increase of normal cell telomere was obtained by a single optimal dose of 1.25-12.5 mg. This was examined in 50 people, both males and females, between the ages of 20-80 years old. When one optimal dose was given to each individual, the average telomere amount in normal tissues, measured in Bi-Digital O-Ring Test units, often increased from anywhere between 25-300 ng to between 500-530 ng. Cancer cell telomere reduced from higher than 1100 ng to less than 1 yg (=10(-24) g) with equally significant normalization of abnormal cancer parameters (such as Integrin alpha5beta1, Oncogen C-fosAb2, Acetylcholine, etc.). Circulatory improvement and an increase in grasping force of up to 25% were also detected, along with the changing of a few white hairs to black hairs. The beneficial effects of one optimal dose of DHEA generally lasted between 1 to 4 months, though in some individuals it lasted for a much shorter period of time due to a number of negative factors such as excessive stress/work, excessive exposure to low temperatures and toxic substances, or use of common pain medicines. On the other hand, if a patient took an excessive dose of DHEA, the amount of normal cell telomere decreased, while there was an increase in cancer cell telomere. It was found that those who took an overdose of 25-50 mg daily for more than 3 months had a high incidence of cancer of the prostate gland, breast, colon, lung, and stomach. Also, when the average normal cell telomere levels were less than 110 ng, compared with a normal value of 120-130 ng, and when DHEA in different parts of the body was also extremely low (less than 1-2 ng), one could suspect the possible presence of a malignant tumor somewhere in the body. When normal cell telomere was less than 110 ng, most individuals felt very weary with marked tiredness in the eyes, and grasping force was often reduced.

Adjuvants, Immunologic↗
PubMed2002

Dehydroepiandrosterone (DHEA) as a possible source for estrogen formation in bone cells: correlation between bone mineral density and serum DHEA-sulfate concentration in postmenopausal women, and the presence of aromatase to be enhanced by 1,25-dihydroxyvitamin D3 in human osteoblasts.

A significant positive correlation between bone mineral density (BMD) and serum dehydroepiandrosterone sulfate (DHEA-S) was found in 120 postmenopausal women (51-99 years old) but no correlation was seen between BMD and serum estradiol. In subset analysis, strong positive correlation of serum DHEA-S and estrone with BMD was observed in postmenopausal women aged less than 69 years old. To study a possible role of DHEA-S in preventing osteoporosis, we characterized aromatase activity converting androgens to estrogens in human osteoblasts, because postmenopausal women maintain considerable levels of adrenal androgens. Glucocorticoids at 10(-9) to 10(-7) M induced transiently the expression of and the enzymatic activity of aromatase cytochrome P450 (P450AROM) in primary cultured osteoblasts. 1,25-Dihydroxyvitamin D3 (1,25-(OH)(2)D(3)) alone did not induce the aromatase activity, but enhanced and maintained the glucocorticoid-induced P450AROM gene expression. Analysis of the activity of P450AROM gene 1b (I.4) promoter, which is used dominantly in human osteoblasts, indicated that the region from -888 bp to -500 bp, which does not contain a typical vitamin D responsive element, is responsible for the enhancing effect of 1,25-(OH)(2)D(3). These results may suggest that adrenal androgen, DHEA, is converted to estrone in osteoblast by P450AROM, which is positively regulated by glucocorticoid and 1,25-(OH)(2)D(3), and is important in maintaining BMD in the sixth to the seventh decade, after menopause.

24,25-Dihydroxyvitamin D 3↗
PubMed1981

Effect of prolactin on the secretion of dehydroepiandrosterone (DHEA), its sulfate (DHEA-S), and cortisol by the human fetal adrenal in vitro.

The effect of prolactin on the secretions of dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) as well as that of cortisol were studied in vitro in order to investigate the possible regulatory role of prolactin on steroidogenesis of the human fetal adrenal at mid-gestational age. The addition of 0.5 microgram/ml of human prolactin to the incubation medium produced a significant (P less than 0.05) increase in DHEA, DHEA-S, and cortisol secretion. These results indicate that prolactin has a regulatory role in steroidogenesis in the human fetal adrenal at mid-gestation.

Adrenal Glands↗
PubMed1986

Pituitary function and DHEA-S in male acne and DHEA-S, prolactin and cortisol before and after oral contraceptive treatment in female acne.

Pituitary function (TRH-LHRH stimulation test) was investigated in male acne patients and serum levels of dehydroepiandrosterone sulphate (DHEA-S), sex hormone binding globulin (SHBG) and other biochemical parameters were investigated in male acne patients and in female acne patients before and after treatment with an oral contraceptive. The TRH-LHRH stimulation test was performed with 15 male patients suffering from severe cystic acne and 7 healthy volunteers. Basal and stimulated prolactin, LH and FSH levels were statistically similar in the patients and control groups. However, the stimulated LH levels of the patients were 60% higher than those in controls. SHBG levels were significantly) higher in the patient group compared to those in the control group. Thirty-three female acne patients were randomly divided into two groups and treated for six months with an oral contraceptive containing 0.030 mg ethinylestradiol (EE) plus 0.150 mg levonorgestrel or 0.150 mg levonorgestrel. After six months' treatment a 30% decrease in DHEA-S levels were observed in the desogestrel/EE group and a 15% decrease in the levonorgestrel/EE group; the difference was not statistically significant. At the same time serum total cortisol increased by 75-100% and free testosterone fell by 30-40% in both groups, whereas SHBG elevated 250% in the desogestrel/EE group and 30% in the levonorgestrel/EE group. Acne improved significantly in both groups, desogestrel/EE showing greater improvement. A decrease in SHBG and increase in DHEA-S levels appear to be the most common hormonal changes in acne. Oral contraceptive treatment induces an increase in SHBG and decrease in DHEA-S and also improves acne.

Acne Vulgaris↗
PubMed2005

Theoretical study of DHEA: comparative HF and DFT calculations of the electronic properties of a complex between DHEA and serotonin.

Molecular parameters (interatomic distances and angles, total atomic charge, dipole moments) of DHEA (Dehydroepiandrosterone), serotonin and of their putative complex including its heat of formation, have been computed in an ab initio comparative study involving HF and DFT calculations. The 6-31G* basis set and the B3LYP functional were employed. The aim of this study is to emphasize by DFT calculation the possible existence of a complex between DHEA and serotonin that may have the properties of a new drug. A Natural Bond Orbital analysis description offers supplementary details for the structure of the molecular units and their interaction.

Binding Sites↗
PubMed1993

Inhibition of HIV-1 latency reactivation by dehydroepiandrosterone (DHEA) and an analog of DHEA.

The initial infection with human immunodeficiency virus type 1 (HIV-1) in most individuals usually results in the establishment of a latent or chronic infection before eventual progression toward acquired immunodeficiency syndrome. HIV-1 can also establish a latent or persistent infection in some T cell lines that show minimal constitutive virus expression. However, activation of the T cell lines leading to enhanced HIV-1 replication can be induced by antigens, mitogens, and cytokines (tumor necrosis factor alpha [TNF-alpha], interleukin 1, and interleukin-2). Various gene products from other viruses (HTLV-1, HSV, EBV, CMV, HBV, and HHV-6) can also enhance HIV-1 long terminal repeat (LTR)-driven reporter gene activity. On the basis of these observations, it has been proposed that reactivation of latent HIV-1 harbored in chronically infected T lymphocytes, monocytes, or macrophages plays an important role in the pathogenesis of AIDS. So far, there are no drugs or therapy available that can provide protection against HIV-1 latency reactivation. ACH-2, derived from a human T cell line (CEM), is chronically infected with HIV-1, with low levels of constitutive virus expression. ACH-2 can be converted to productive infection by stimulation of the cells with 12-O-tetradecanoylphorbol-13-acetate (TPA), mitogen or cytokines (TNF-alpha), or infection with HSV. Therefore the ACH-2 cell line is a good candidate for studying the effects of drugs on HIV-1 activation. Previously, we have reported that DHEA and synthetic analogs of DHEA can be modest inhibitors of HIV-1 IIIB replication in phytohemagglutinin-stimulated peripheral blood lymphocyte cultures.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗