Plasma Concentrations Of Dehydroepiandrosterone Research Articles

Improvement of several stress response and sleep quality hormones in men and women after sleeping in a bed that protects against electromagnetic fields

BackgroundThe electromagnetic fields (EMFs) emitted by the technologies affect the homeostatic systems (nervous, endocrine, and immune systems) and consequently the health. In a previous work, we observed that men and women, after 2 months of using a bed with a registered HOGO system, that prevents and drain EMFs, improved their immunity, redox and inflammatory states and rejuvenated their rate of aging or biological age. Since, EMFs can act as a chronic stressor stimulus, and affect the sleep quality. The objective of this work was to study in men and women (23–73 years old) the effect of sleeping for 2 months on that bed in the blood concentrations of several hormones related to stress response and sleep quality as well as to corroborate the rejuvenation of their biological age.MethodsIn 18 men and women, plasma concentration of cortisol, dehydroepiandrosterone (DHEA), catecholamines (epinephrine, norepinephrine and dopamine), serotonin, oxytocin and melatonin were analyzed before and after 2 months of using the HOGO beds. A group of 10 people was used as placebo control. In another cohort of 25 men (20 experimental and 5 placebo), the effects of rest on the HOGO system on the concentration of cortisol and testosterone in plasma were studied. In all these volunteers, the biological age was analyzed using the Immunity Clock model.ResultsThere is a significant increase in plasma concentration of DHEA, norepinephrine, serotonin, oxytocin, and melatonin as well as in testosterone, after resting for 2 months in that bed with the EMFs avoiding system. In addition, decreases in Cortisol/DHEA and Testosterone/cortisol ratio and plasma dopamine concentration were observed. No differences were found in placebo groups. In all participants that slept on HOGO beds, the biological age was reduced.ConclusionsSleeping in a bed that isolates from EMFs and drain them can be a possible strategy to improve the secretion of hormones related to a better response to stress and sleep quality, which means a better endocrine system, and consequently better homeostasis and maintenance of health. This fact was confirmed with the slowdown in the rate of aging checked with a rejuvenation of the biological age.

Abnormal Plasma Levels of Steroids and Their Ratios in Patients With Prurigo Nodularis: A Pilot Study.

Background: It has been suggested that cortisol levels are abnormal in chronic urticaria and atopic dermatitis, but other steroids, such as dehydroepiandrosterone (DHEA) and testosterone, are still unknown, and whether these hormones affect the maintenance of skin homeostasis or the pathogenesis of skin diseases is not fully understood. Limited data are available on steroid levels in prurigo nodularis (PN)-related research, and no study has examined the association between pruritus severity and steroid levels in PN patients. Aims: This pilot study aimed to investigate the differences in the levels of five steroids combined with their ratios in plasma between PN patients and controls and to examine the associations between the biomarkers and pruritus severity. Methods: Plasma concentrations of five steroids, including cortisol, cortisone, testosterone, progesterone, and dehydroepiandrosterone (DHEA), in 36 patients with PN were compared with concentrations in thirty-six and matched healthy controls. The concentrations of steroids were quantitated using liquid chromatography-tandem mass spectrometry. The PN symptoms, including pruritus severity, pain, and life quality, were assessed with the use of the visual analog scale, prurigo score index, numerical rating scale, and verbal rating scale and dermatology life quality index scores. Results: In comparison with controls, PN patients had lower levels of plasma cortisol and cortisone, which negatively correlated with PN symptoms. PN patients had higher levels of cortisone and testosterone to cortisol, which positively correlated with pruritus severity. Additionally, there were no significant differences in plasma concentrations of DHEA and testosterone between the two groups. We found no correlation between plasma concentrations of DHEA and testosterone and pruritus severity. Conclusion: This pilot study suggests that there may be abnormalities in peripheral blood levels of cortisol, and cortisone and the ratios of cortisone and testosterone to cortisol in patients with PN, and they are related to pruritus severity. The plasma concentrations of testosterone and DHEA may be not abnormal in PN patients and may not be associated with pruritus severity.

Oral Contraceptive Use Impairs Muscle Gains in Young Women

Riechman, SE and Lee, CW. Oral contraceptive use impairs muscle gains in young women. J Strength Cond Res 36(11): 3074-3080, 2022-Many active young women use oral contraceptives (OCs), yet their effects on the body composition and exercise performance have not been thoroughly studied. We examined the effects of OCs on muscle responses to a standardized resistance exercise training (RET) program. Two groups of young healthy women (18-29 years old, non-OC: n = 38, OC: n = 34) underwent 10 weeks of whole-body RET (3 days·wk -1 , 3 sets, 6-10 repetitions, at 75% of maximum strength, 13 exercises). Body composition was determined using hydrostatic weighing, and blood samples were taken before and after training to measure dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), IGF-1, and cortisol levels. There were significant differences in lean mass gains between the groups (non-OC: 3.5 ± 0.4% vs. OC: 2.1 ± 0.5% and non-OC: 1.6 ± 0.2 kg vs. OC: 1.0 ± 0.2 kg, p < 0.05). Plasma concentrations of DHEA, DHEAS, and IGF-1 were significantly lower, and cortisol levels were higher in the OC group before and after training ( p < 0.05). In addition, there were significant differences in lean mass gains depending on the androgenicity of progestin between the non-OC and medium-high groups (non-OC: 1.6 ± 0.2 kg, Low = 1.1 ± 0.2 kg, med-high = 0.3 ± 0.5 kg, p < 0.05). Oral contraceptive use impaired lean mass gains in young women after RET and was associated with lower DHEA, DHEAS, and IGF-1 and higher cortisol. The diminished lean mass gain may be related to the effect of OCs on anabolic and catabolic hormone levels or the androgenicity of progestin that may bind to androgen receptors and inhibit its function.

Evidence for fasting induced extra-adrenal steroidogenesis in the male brown anole, Anolis sagrei.

Glucocorticoids (GCs) and dehydroepiandrosterone (DHEA) are steroids secreted by the adrenal glands into circulation to effect distant target tissues and coordinate physiological processes. This classic systemic view of steroids has been challenged by evidence that other tissues can independently synthesize their own steroids. Little is known however regarding circumstances that can promote this extra-adrenal steroidogenesis. Here we tested if fasting can induce tissues to increase GC and DHEA synthesis in the brown anole lizard Anolis sagrei. Lizards fasted for eight days lost body mass and increased fatty acid oxidation. Fasting also increased plasma concentrations of DHEA and corticosterone, but not cortisol. Corticosterone concentration within the adrenals, heart, intestines, lungs and liver exceeded that in plasma, with the latter two increasing with fasting. Levels of DHEA in the adrenals and heart were higher than in plasma, but no significant effect of fasting was observed, expect for a noticeable increase in intestinal DHEA. Two steroidogenic genes, the steroidogenic acute regulatory (Star) protein and Cyp17a1, a cytochrome P450 enzyme, were expressed in several tissues including the liver, lungs and intestines, which were increased with fasting. Continued research should aim to test for expression of additional enzymes further along the steroidogenic pathway. Nonetheless these data document potential extra-adrenal steroidogenesis as a possible mechanism for coping with energy shortages, although much work remains to be done to determine the specific roles of locally synthesized steroids in each tissue.

Behavioral and steroidogenic pharmacology of phenyl ring substituted etomidate analogs in rats

BackgroundCushing’s syndrome is an endocrine disorder characterized by the overproduction of adrenocortical steroids. Steroidogenesis enzyme inhibitors are the mainstays of pharmacological treatment. Unfortunately, they produce significant side effects. Among the most potent inhibitors is the general anesthetic etomidate whose GABAA receptor-mediated sedative-hypnotic actions restrict use. In this study, we defined the sedative-hypnotic and steroidogenesis inhibiting actions of etomidate and four phenyl-ring substituted etomidate analogs (dimethoxy-etomidate, isopropoxy-etomidate, naphthalene-etomidate, and naphthalene (2)-etomidate) that possess negligible GABAA receptor modulatory activities.MethodsIn the first set of experiments, male Sprague-Dawley rats were assessed for loss of righting reflexes (LoRR) after receiving intravenous boluses of either etomidate (1 mg/kg) or an etomidate analog (40 mg/kg). In the second set of experiments, rats were assessed for LoRR and their abilities to produce adrenocortical and androgenic steroids after receiving 2-h infusions (0.5 mg kg− 1 min− 1) of either etomidate or an etomidate analog.ResultsAll rats that received etomidate boluses or infusions had LoRR that persisted for minutes or hours, respectively. In contrast, no rat that received an etomidate analog had LoRR. Compared to rats in the vehicle control group, rats that received etomidate analog infusions had plasma corticosterone and aldosterone concentrations that were reduced by 80–84% and 68–94%, respectively. Rats that received etomidate infusions had plasma corticosterone and aldosterone concentrations that were also significantly reduced (by 92 and 96%, respectively). Rats that received etomidate or isopropoxy-etomidate had significant reductions (90 and 57%, respectively) in plasma testosterone concentrations whereas those that received naphthalene-etomidate had significant increases (1400%) in plasma dehydroepiandrosterone concentrations. Neither etomidate nor any etomidate analog significantly affected plasma androstenedione and dihydrotestosterone concentrations.ConclusionsOur studies demonstrate that the four phenyl-ring substituted etomidate analogs form a novel class of compounds that are devoid of sedative-hypnotic activities and suppress plasma concentrations of adrenocortical steroids but vary in their effects on plasma concentrations of androgenic steroids.

Aerobic exercise training and dehydroepiandrosterone administration increase testicular sex steroid hormones and enhance reproductive function in high-sucrose-induced obese rats

This study assessed the effects of chronic dehydroepiandrosterone (DHEA) administration and exercise training on testicular sex steroid hormone levels and reproductive function in high-sucrose induced obese rats. After 14 weeks of a high-sucrose diet, Wistar male rats were assigned randomly to the control, exercise training (running at 25 m/min for 1 h, 5 days/week), DHEA administration, and combined exercise training and DHEA administration groups (n = 7 each group). Six weeks of DHEA administration and/or exercise training significantly increased plasma concentrations of DHEA and 5α-dihydrotestosterone (DHT) and epididymis DHEA concentrations; however, the expression of steroidogenic enzymes, such as 3β-hydroxysteroid dehydrogenase (HSD), 17β-HSD, and 5α-reductase, did not change following any interventions. Procathepsin L expression, which involved sperm maturation, was significantly lower in the DHEA and combination groups, and glutathione peroxidase 4 (GPx4) expression, which plays a role in protecting sperms from oxidative stress, was significantly increased in the DHEA administration group. Additionally, exercise training and/or DHEA administration-induced increase in procathepsin L expressions were significantly correlated with the epididymis DHEA concentrations. These findings suggest that exercise training and/or DHEA administration-induced increase in epididymis DHEA concentration may improve impairment of reproductive function in high-sucrose obese rats. Additionally, exercise training and/or DHEA administration-induced increase in DHEA concentration may have a role in testicular-specific action, which included protective role from exercise-induced oxidant damage as well as contributed to the enhancement of sperm modification and maturation in obese rats.

Ontogeny of the Adrenal Gland in the Spiny Mouse, With Particular Reference to Production of the Steroids Cortisol and Dehydroepiandrosterone

Synthesis of the androgen dehydroepiandrosterone (DHEA) by the fetal adrenal gland is important for placental estrogen production and may also be important for modulating the effects of glucocorticoids on the developing brain. The presence of cortisol in spiny mouse (Acomys cahirinus) blood led us to determine whether the adrenal gland of this precocial rodent also synthesized DHEA. Cytochrome P450 enzyme 17α-hydroxylase/17,20-lyase (P450c17), cytochrome-b5 (Cytb5), and 3β-hydroxysteroid dehydrogenase (3βHSD) were detected in the adrenal gland from 30 days gestation (term = 39 days), and DHEA, cortisol, and aldosterone were detected in fetal plasma from this time. Plasma DHEA concentrations increased 4-fold, whereas cortisol concentrations decreased from day 30 of gestation until the day of birth. Explant culture of fetal adrenal tissue showed that DHEA was produced from exogenous pregnenolone, and thus, the DHEA in the fetal circulation is likely to be of fetal origin. Clear zonation of the fetal adrenal cortex was evident by 38 days gestation when expression of Cytb5 was present throughout the cortex, and coexpression of P450c17 and Cytb5 occurred in the zona reticularis and fasciculata. 3βHSD was expressed in the cortex from at least 30 days gestation and decreased as term approached, consistent with the fall of cortisol in late gestation in this species. These results show that the spiny mouse adrenal gland, like that of the human fetus, can synthesize and secrete DHEA from at least 30 days (relative gestation length, 30 days of a 39-day gestation, 0.76) of gestation, and DHEA may have important roles in placental biosynthesis of estrogens and in modulating the actions of glucocorticoids in the developing brain in this species.

Altered plasma concentrations of sex hormones in cats infected by feline immunodeficiency virus or feline leukemia virus

Gender differences may affect human immunodeficiency virus (HIV) infection in humans and may be related to fluctuations in sex hormone concentration. The different percentage of male and female cats observed to be infected by feline leukemia virus (FeLV) or feline immunodeficiency virus (FIV) has been traditionally explained through the transmission mechanisms of both viruses. However, sexual hormones may also play a role in this different distribution. To study this possibility, 17β-estradiol, progesterone, testosterone, and dehydroepiandrosterone (DHEA) concentrations were analyzed using a competitive enzyme immunoassay in the plasma of 258 cats naturally infected by FIV (FIV +), FeLV (FeLV +), or FeLV and FIV (F −F +) or negative for both viruses, including both sick and clinically healthy animals. Results indicated that the concentrations of 17β-estradiol and testosterone were significantly higher in animals infected with FIV or FeLV ( P < 0.05) than in negative cats. Plasma concentrations of DHEA in cats infected by either retrovirus were lower than in negative animals ( P < 0.05), and F −F + cats had significantly lower plasma values than monoinfected cats ( P < 0.05). No significant differences were detected in the plasma concentration of progesterone of the four groups. No relevant differences were detected in the hormone concentrations between animal genders, except that FIV + females had higher DHEA concentrations than the corresponding males ( P < 0.05). In addition, no differences were observed in the hormone concentrations between retrovirus-infected and noninfected animals with and without clinical signs. These results suggest that FIV and FeLV infections are associated with an important deregulation of steroids, possibly from early in the infection process, which might have decisive consequences for disease progression.

Seasonal Androgen Cycles in Adult Male American Alligators (Alligator mississippiensis) from a Barrier Island Population1

The seasonal patterns of two primary plasma androgens, testosterone (T) and dehydroepiandrosterone (DHEA), were assessed in adult male alligators from the Merritt Island National Wildlife Refuge, a unique barrier island environment and home to the Kennedy Space Center in Florida. Samples were collected monthly from 2008 to 2009, with additional samples collected at more random intervals in 2007 and 2010. Plasma T concentrations peaked in April, coincident with breeding and courtship, and declined rapidly throughout the summer. Seasonal plasma T patterns in smaller though reproductively active adult males differed from those in their larger counterparts during the breeding season. Both size classes showed significant increases in plasma T concentration from February to March, at the beginning of the breeding season. However, smaller adults did not experience the peak in plasma T concentrations in April that were observed in larger adults, and their concentrations were significantly lower than those of larger males for the remainder of the breeding season. Plasma DHEA concentrations peaked in May and were significantly reduced by June. This is the first study to demonstrate the presence of DHEA in a crocodilian, and the high plasma DHEA concentrations that paralleled the animals' reproductive activity suggest a reproductive and/or behavioral role in adult male alligators. Similar to androgen variations in some birds, plasma DHEA concentrations in the alligators were considerably higher than T concentrations during the nonbreeding season, suggesting a potential role in maintaining nonbreeding seasonal aggression.

The effect of long-term DHEA treatment on glucose metabolism, hydrogen peroxide and thioredoxin levels in the skeletal muscle of diabetic rats

Dehydroepiandrosterone (DHEA) is an endogenous steroid hormone involved in a number of biological actions. This study shows the effects of DHEA on glucose metabolism, hydrogen peroxide and thioredoxin levels in the skeletal muscle of control and diabetic rats. Control and diabetic rats were chronically treated with DHEA (10 mg/kg) diluted in oil. Plasma concentration of DHEA and glucose, glucose uptake and oxidation, hydrogen peroxide, GLUT4, Akt and thioredoxin (Trx) was measured in the muscle. Results showed that there was a decrease in blood glucose in diabetic rats, probably linked to an increase in the glucose oxidation by the muscle or glucose uptake by some tissues. Despite the increase in the expression of GLUT4 in DHEA-treated rats, the glucose uptake was only higher in the control rats, showing that the glucose transporter may be present but not functional in the diabetic rats. The low expression of Trx due to diabetes became even lower with DHEA treatment. Although the reduction in blood glucose may be favorable, the decrease in Akt and Trx displays an environment conducive to redox imbalance. Thus, further studies are needed to ascertain the effects of DHEA treatment in diabetic rats.

Blood concentrations of serotonin, cortisol and dehydroepiandrosterone in aggressive dogs

Canine aggression directed towards people is the most frequent reason for referral to behaviour practices. In order to provide new and improved diagnostic and therapeutic approaches for this problem, it is necessary to make an in-depth investigation of the biological basis of aggression in this species. The serotonergic system and the hypothalamic–pituitary–adrenal (HPA) axis are believed to play an important role in controlling aggression. The aim of the present study was to investigate both systems in aggressive ( n = 80) and control non-aggressive ( n = 19) dogs through the assessment of peripheral parameters, namely serum serotonin (5-HT), and plasma cortisol and dehydroepiandrosterone (DHEA). Moreover, the effect of the category of aggression and gender was investigated. Aggressive dogs showed significantly lower serum concentrations of 5-HT than non-aggressive dogs (278.5 ng/ml vs. 387.4 ng/ml, P < 0.01). The lowest 5-HT concentrations were found in the group of dogs showing defensive forms of aggression. Aggressive animals showed significantly higher plasma concentrations of cortisol than non-aggressive dogs (21.4 ng/ml vs. 10.6 ng/ml, P = 0.05). Finally, males as a whole showed significantly higher plasma concentrations of DHEA and DHEA/cortisol ratio values than did females (DHEA: 90.9 ng/ml vs. 29.8 ng/ml, P < 0.05; ratio: 9.5 vs. 3.8, P < 0.01). The present results suggest that aggressive dogs might differ from non-aggressive dogs in the activities of the serotonergic system and the HPA axis.

Plasma Dehydroepiandrosterone and Risk of Myocardial Infarction in Women

In this study we prospectively evaluated the relationships between plasma concentrations of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) and subsequent myocardial infarction in women. Using case-control sampling, we selected participants from the Nurses' Health Study cohort. Blood samples were collected from 1989 to 1990 when the women were 43 to 69 years old. During follow-up through June 1998, 239 women were diagnosed with myocardial infarction (fatal and nonfatal). We matched cases 1:2 by age, cigarette smoking status, fasting status, and month of blood collection and used conditional logistic regression to adjust for potential confounders, including anthropometric factors and dietary intake. Baseline median (10th, 90th percentiles) concentrations of DHEA were 17.1 (4.3, 46.7) nmol/L among women who subsequently developed myocardial infarction and 16.6 (6.1, 37.9) among controls. The risk of myocardial infarction increased with plasma concentrations of DHEA and its sulfate. Women in the highest DHEA quartile had a rate ratio (RR) of 1.27 (95% CI 0.92-1.74, P for trend = 0.008) for myocardial infarction compared with those in the lowest quartile, after adjusting for covariates. The results did not vary significantly by menopausal status, postmenopausal estrogen therapy, fasting status, or age at time of blood collection. Similar relationships between concentrations of DHEA-S and risk were observed, with an RR of 1.58 (95% CI 1.13-2.21; P for trend = 0.06) for myocardial infarction in the highest vs lowest quartile. We observed a modest positive relationship between plasma concentrations of DHEA and its sulfate and the risk of subsequent myocardial infarction among predominantly postmenopausal women.

Plasma DHEA levels in wild, territorial red squirrels: Seasonal variation and effect of ACTH

In many species, territorial behavior is limited to the breeding season and is tightly coupled to circulating gonadal steroid levels. In contrast, both male and female red squirrels ( Tamiasciurus hudsonicus) are highly aggressive in both the breeding and non-breeding seasons in defense of food stores on their individual territories throughout the boreal and northern forests of North America. Dehydroepiandrosterone (DHEA), an androgen precursor, is secreted from the adrenal cortex in some mammals, and DHEA has been linked to aggression in non-breeding songbirds. Here, we examined plasma DHEA levels in a natural population of red squirrels in the Yukon, Canada. Plasma DHEA levels in both males and females reached high concentrations (up to 16.952 ng/ml in males and 14.602 ng/ml in females), markedly exceeding plasma DHEA concentrations in laboratory rats and mice and similar to plasma DHEA concentrations in some primates. Circulating DHEA levels showed both seasonal and yearly variation. Seasonal variation in male plasma DHEA levels was negatively correlated with testes mass. Yearly variation in male DHEA levels was positively correlated with population density. In both males and females, circulating DHEA rapidly increased after ACTH treatment, implying an adrenal origin. This is the first examination of plasma DHEA concentrations in a wild rodent and the first field experiment on the regulation of plasma DHEA in any wild mammal. These data lay the foundation for future studies on the role of DHEA in non-breeding territoriality in this species and other mammals.

Elevation of the cortisol/dehydroepiandrosterone ratio in schizophrenia patients

Dehydroepiandrosterone (DHEA) and its sulfate derivative DHEA-S are neurosteroids, produced in the brain, and neuroactive steroids, produced in the adrenals and affecting the brain. We compared the ratios of serum cortisol/DHEA or DHEA-S in schizophrenia patients with normal subjects, and determined the correlation of these ratios with psychopathology and distress. Early morning plasma concentrations of DHEA, DHEA-S, and cortisol were determined by radioimmunassay in 40 medicated schizophrenia inpatients, and 15 healthy subjects with similar age and sex distribution. Subjects were assessed for psychopathology using the Positive and Negative Syndrome Scale (PANSS) and the Montgomery and Asberg Depression Rating Scale (MADRS), anxiety, anger, emotional and somatic distress levels. Schizophrenia inpatients demonstrated significantly higher levels of state and trait anxiety, anger expression index, emotional and somatic self-reported distress scores. Cortisol/DHEA and cortisol/DHEA-S ratios were significantly higher in schizophrenia patients than in healthy comparison subjects. Both ratios correlated positively with age and duration of illness; cortisol/DHEA-S ratio also showed positive association with age of illness onset. When age, illness duration and age of onset were controlled, cortisol/DHEA-S ratio significantly correlated with severity of depression (MADRS, r=0.33, p=0.048), state and trait anxiety (r=0.43, p=0.008 and r=0.40, p=0.014, respectively), trait anger (r=0.41, p=0.012), angry temperament (r=0.46, p=0.004), anger expression index (r=0.36, p=0.033), and hostility (r=0.42, p=0.010). No significant association was found between these ratios and severity of psychopathology, and type or dosage of antipsychotic agents. Thus, elevated cortisol/DHEA and/or cortisol/DHEA-S ratios in schizophrenia patients are positively associated with higher scores for anxiety and anger, depression and hostility, age and age of onset/duration of illness, but are independent of severity of psychopathology (PANSS) and antipsychotic treatment.

The increase in plasma C 19Δ 5 steroids in subcutaneous abdominal and jugular veins of dairy cattle during pregnancy is unrelated to estrogenic activity

Plasma concentrations of dehydroepiandrosterone (DHEA), 5-androstene-3β,17β-diol (AED), and 17β-estradiol (E2) in dairy cows and heifers and AED binding to uterine cytosolic estrogen receptor (ER) were studied. Plasma samples were collected from the subcutaneous abdominal (SA) and jugular (J) veins of heifers and cows in the non-pregnant state and at 15–45, 90–120, 180–210, and 250–280 days of pregnancy ( N=5–12). Plasma DHEA, AED, and E2 were determined by RIA. DHEA and AED significantly increased ( P<0.001) in heifers and cows throughout pregnancy. The stage of pregnancy significantly ( P<0.001) affected the three steroids in heifers and cows. Plasma DHEA increased throughout pregnancy in both heifers and cows, and in heifers it was significantly greater in SA than in J veins at 90–120 days ( P<0.01). Plasma AED was greater in heifers than in cows in J veins at 90–120 days ( P<0.01) and 180–210 days ( P<0.05), and in SA veins, at 15–45 days ( P<0.01) and 90–120 days ( P<0.05). In heifers, circulating AED showed concentration values significantly greater than those in non-pregnant animals from 90 to 120 days ( P<0.05) and was significantly greater in SA than in J veins at 90–120 days ( P<0.05). In cows, plasma AED was significantly greater than in non-pregnant animals at 250–280 days ( P<0.01). In heifers, plasma E2 was significantly greater in the SA than in the J veins from 180–210 to 250–280 days ( P<0.01). In cows, differences between E2 plasma concentrations in J and SA veins were observed only at 250–280 days of pregnancy. At 250–280 days, in both animal types plasma E2 was significantly greater than in non-pregnant animals ( P<0.001). We suggest that AED originates primarily from the feto-placental unit, while mammary E2 synthesis near term can affect plasma concentrations. Binding data showed that AED is a weak competitor for cytosolic ER (IC 50 range: 1.44×10 −5 to 3.71×10 −5 M). These results suggest that a direct estrogenic activity for AED is unlikely in dairy cattle, and the physiological role of AED needs to be elucidated.

Territorial aggression and hormones during the non-breeding season in a tropical bird

The hormonal control of territorial aggression in male and female vertebrates outside the breeding season is still unresolved. Most vertebrates have regressed gonads when not breeding and do not secrete high levels of sex steroids. However, recent studies implicate estrogens in the regulation of non-breeding territoriality in some bird species. One possible source of steroids during the non-breeding season could be the adrenal glands that are known to produce sex steroid precursors such as dehydroepiandrosterone (DHEA). We studied tropical, year-round territorial spotted antbirds ( Hylophylax n. naevioides) and asked (1) whether both males and females are aggressive in the non-breeding season and (2) whether DHEA is detectable in the plasma at that time. We conducted simulated territorial intrusions (STIs) with live decoys to male and female free-living spotted antbirds in central Panama. Non-breeding males and females displayed robust aggressive responses to STIs, and responded more intensely to decoys of their own sex. In both sexes, plasma DHEA concentrations were detectable and higher than levels of testosterone (T) and 17β-estradiol (E 2). In males, plasma DHEA concentrations were positively correlated with STI duration. Next, we conducted STIs in captive non-breeding birds. Captive males and females displayed robust aggressive behavior. Plasma DHEA concentrations were detectable in both sexes, whereas T was non-detectable (E 2 was not measured). Plasma DHEA concentrations of males were positively correlated with aggressive vocalizations and appeared to increase with longer STI durations. We conclude that male and female spotted antbirds can produce DHEA during the non-breeding season and DHEA may serve as a precursor of sex steroids for the regulation of year-round territorial behavior in both sexes.

Elevation of the cortisol/dehydroepiandrosterone ratio in schizophrenia patients

Dehydroepiandrosterone (DHEA) and its sulfate derivative DHEA-S are neurosteroids, produced in the brain, and neuroactive steroids, produced in the adrenals and affecting the brain. We compared the ratios of serum cortisol/DHEA or DHEA-S in schizophrenia patients with normal subjects, and determined the correlation of these ratios with psychopathology and distress. Early morning plasma concentrations of DHEA, DHEA-S, and cortisol were determined by radioimmunassay in 40 medicated schizophrenia inpatients, and 15 healthy subjects with similar age and sex distribution. Subjects were assessed for psychopathology using the Positive and Negative Syndrome Scale (PANSS) and the Montgomery and Asberg Depression Rating Scale (MADRS), anxiety, anger, emotional and somatic distress levels. Schizophrenia inpatients demonstrated significantly higher levels of state and trait anxiety, anger expression index, emotional and somatic self-reported distress scores. Cortisol/DHEA and cortisol/DHEA-S ratios were significantly higher in schizophrenia patients than in healthy comparison subjects. Both ratios correlated positively with age and duration of illness; cortisol/DHEA-S ratio also showed positive association with age of illness onset. When age, illness duration and age of onset were controlled, cortisol/DHEA-S ratio significantly correlated with severity of depression (MADRS, r=0.33, p=0.048), state and trait anxiety ( r=0.43, p=0.008 and r=0.40, p=0.014, respectively), trait anger ( r=0.41, p=0.012), angry temperament ( r=0.46, p=0.004), anger expression index ( r=0.36, p=0.033), and hostility ( r=0.42, p=0.010). No significant association was found between these ratios and severity of psychopathology, and type or dosage of antipsychotic agents. Thus, elevated cortisol/DHEA and/or cortisol/DHEA-S ratios in schizophrenia patients are positively associated with higher scores for anxiety and anger, depression and hostility, age and age of onset/duration of illness, but are independent of severity of psychopathology (PANSS) and antipsychotic treatment.

In vivo dehydroepiandrosterone restores age-associated defects in the protein kinase C signal transduction pathway and related functional responses.

Elderly subjects are at increased risk of pneumonia, influenza, and tuberculosis. Besides the known age-related decrease in mechanisms for mechanical clearance of the lungs, impaired alveolar macrophage function contributes to the increased risk of illness in the elderly. We have previously shown that age-induced macrophage immunodeficiencies are associated with a defective system for anchoring protein kinase C. Castration of young male rats produces effects on alveolar macrophages similar to those of aging, suggesting a relationship between circulating sex hormones, particularly androgens, and the decreases in the receptor for activated C kinase (RACK-1) and macrophage function observed. The aging process in humans and rats is associated with a decline in the plasma concentrations of dehydroepiandrosterone (DHEA) and its sulfate, among other steroid hormones. We report here that in vitro and in vivo administration of DHEA to rats restores the age-decreased level of RACK-1 and the LPS-stimulated production of TNF-alpha in alveolar macrophages. DHEA in vivo also restores age-decreased spleen mitogenic responses and the level of RACK-1 expression. These findings suggest that the age-related loss in immunological responses, linked to defective pathways of signal transduction, are partially under hormonal control and can be restored by appropriate replacement therapy.

Longitudinal changes in dehydroepiandrosterone concentrations in men and women

Dehydroepiandrosterone, an adrenal steroid, has many purported roles in the body and has been used as an oral supplement in the treatment of various illnesses. Because little is known about normal changes over time in dehydroepiandrosterone concentrations, we studied the 5-year change in plasma dehydroepiandrosterone concentrations in 614 free-living adults. Two hundred seventy-three males and 341 females had dehydroepiandrosterone and dehydroepiandrosterone sulfate concentrations measured in 1989 and 1994. Demographic data were also obtained. Dehydroepiandrosterone concentrations differed significantly by sex and 5-year age group. The average decline in dehydroepiandrosterone was 5.6%/year, and the rate of decline was directly related to age but not to sex, measures of adiposity, or serum glucose. Dehydroepiandrosterone sulfate concentrations differed significantly by sex and age group. The average decline in the sulfated hormone was 2.0%/year and was not related to age, sex, measures of adiposity, or serum glucose. Knowledge of the natural course of age-related changes in dehydroepiandrosterone and dehydroepiandrosterone sulfate concentrations is essential to our understanding of the relationship of dehydroepiandrosterone to chronic diseases.

Response of dehydroepiandrosterone to corticotropin-releasing hormone stimulation in alcohol-dependent subjects

Dehydroepiandrosterone (DHEA) is the most abundant steroid in humans, and has been shown to reduce low-density lipoprotein levels (Nestler et al 1988), alter hepatic enzymatic activity (Cleary 1990), display antidiabetic properties (Coleman et al 1984), and improve memory (Flood et al 1988). Low plasma concentrations of DHEA and DHEA-sulfate (DHEA-S, the major metabolite of DHEA) have been associated with various medical and psychiatric chronic illnesses (Barrett-Connor et al 1986; Lopez et al 1976; Merrill et al 1989; Tourney and Hatfield 1972), as well as early mortality from all causes (Barrett-Connor et al 1986). The adrenal reserve of DHEA, in contrast to that of the glucocorticoids, has also been shown to be attenuated in various disease states (Parker et al 1985). The pathophysiologic states associated with low DHEA levels bear similarities to the disease processes associated with excessive alcohol consumption. We therefore hypothesized that the chronic course of alcoholism may induce disturbances in DHEA secretion similar to those observed in other chronic illnesses. Attenuated levels of DHEA in alcohol-dependent patients could subsequently be causally related to alcohol-associated physiologic impairments.