Effect of dehydroepiandrosterone on oocyte and embryo yields, embryo grade and cell number in IVF

BACKGROUND: The aim of this study was to investigate the effect of treatment with dehydroepiandrosterone (DHEA) on fertility outcomes among women with diminished ovarian reserve. MATERIALS AND METHODS: This is a case-control study in an academically affiliated private infertility centre. Twenty-five women with significantly diminished ovarian reserve had one IVF cycle before and after DHEA treatment, with otherwise identical hormonal stimulation. Women received 75 mg of DHEA daily (25 mg three times daily) for an average of 17.6 +/- 2.13 weeks. We performed a comparison of IVF outcome parameters, before and after DHEA treatment, including peak estradiol (E(2)) levels, oocyte and embryo numbers, oocyte and embryo quality and embryo transfer statistics. RESULTS: Paired analysis of IVF cycle outcomes in 25 patients, who underwent cycles both before and after DHEA supplementation, demonstrated significant increases in fertilized oocytes (P < 0.001), normal day 3 embryos (P = 0.001), embryos transferred (P = 0.005) and average embryo scores per oocyte (P < 0.001) after DHEA treatment. CONCLUSION: This study confirms the previously reported beneficial effects of DHEA supplementation on ovarian function in women with diminished ovarian reserve.     

Dehydroepiandrosterone Supplementation Combined with Whole-Body Vibration Training Affects Testosterone Level and Body Composition in Mice

Dehydroepiandrosterone (DHEA), the most abundant sex steroid, is primarily secreted by the adrenal gland and a precursor hormone used by athletes for performance enhancement. Whole-body vibration (WBV) is a well-known light-resistance exercise by automatic adaptations to rapid and repeated oscillations from a vibrating platform, which is also a simple and convenient exercise for older adults. However, the potential effects of DHEA supplementation combined with WBV training on to body composition, exercise performance, and hormone regulation are currently unclear. The objective of the study is to investigate the effects of DHEA supplementation combined with WBV training on body composition, exercise performance, and physical fatigue-related biochemical responses and testosterone content in young-adult C57BL/6 mice. In this study, male C57BL/6 mice were divided into four groups (n = 8 per group) for 6-weeks treatment: sedentary controls with vehicle (SC), DHEA supplementation (DHEA, 10.2 mg/kg), WBV training (WBV; 5.6 Hz, 2 mm, 0.13 g), and WBV training with DHEA supplementation (WBV+DHEA; WBV: 5.6 Hz, 2 mm, 0.13 g and DHEA: 10.2 mg/kg). Exercise performance was evaluated by forelimb grip strength and exhaustive swimming time, as well as changes in body composition and anti-fatigue levels of serum lactate, ammonia, glucose, creatine kinase (CK), and blood urea nitrogen (BUN) after a 15-min swimming exercise. In addition, the biochemical parameters and the testosterone content were measured at the end of the experiment. Six-week DHEA supplementation alone significantly increased mice body weight (BW), muscle weight, testosterone level, and glycogen contents (liver and muscle) when compared with SC group. DHEA supplementation alone had no negative impact on all tissue and biochemical profiles, but could not improve exercise performance. However, WBV+DHEA supplementation also significantly decreased BW, testosterone level and glycogen content of liver, as well as serum lactate and ammonia levels after the 15-min swimming exercise when compared with DHEA supplementation alone. Although DHEA supplementation alone had no beneficial effect in the exercise performance of mice, the BW, testosterone level and glycogen content significantly increased. On the other hand, WBV training combined with DHEA decreased the BW gain, testosterone level and glycogen content caused by DHEA supplementation. Therefore, WBV training could inhibit DHEA supplementation to synthesis the testosterone level or may decrease the DHEA supplement absorptive capacity in young-adult mice.     

Effects of vitamin D on ovary in DHEA-treated PCOS rat model: A light and electron microscopic study

Aim: The aim of this study was to investigate the effects of vitamin D treatment on ovary in experimentally designed polycystic ovary syndrome of female rats using light and electron microscopic techniques. Methods: Twenty-four female pre-pubertal rats were divided into control, DHEA and DHEA+Vit.D groups. In DHEA group, the PCOS rat model was developed by 6mg/kg/day dehydroepiandrosterone administration as subcutaneously injections. In DHEA+Vit.D group, 6 mg/kg/day DHEA and 120ng/100g/week 1,25(OH)2D3 was performed simultaneously. Controls were injected with vehicle alone. At the end of the 28 days, blood samples were collected and the ovarian tissues were taken for histological examinations. Results: FSH, LH levels, LH/FSH ratio, and testosterone levels showed a significant increase in DHEA group when compared with the control group. Moreover, these measurements were lower in the treatment group than the DHEA group. In DHEA group, increased number of atretic follicles and cystic follicles were seen with light microscopic analysis. Cystic follicles with attenuated granulosa cell layers and thickened theca cell layers and lipid accumulation in interstitial cells were observed by electron microscope. It is observed that atretic and cystic follicles were decreased as a result of vitamin D treatment. Conclusion: Our results indicate the curative role of vitamin D treatment on the androgen excess in PCOS rat model which causes abnormalities in ovarian morphology and functions. Vitamin D has positive effects on the hormonal and structural changes observed in PCOS, but it has been concluded that long-term use may be more beneficial.     

Uses of DHEA in aging and other disease states

Dehydro-3-epiandrosterone is a steroid hormone synthesized in large quantities by the adrenal gland whose physiologic role remains unclear. The effects of DHEA could be estrogenic or androgenic, depending on the hormonal milieu. Low levels of DHEA are associated with aging, cardiovascular disease in men, and an increased risk of pre-menopausal breast and ovarian cancer. High levels of DHEA might increase the risk of postmenopausal breast cancer. Therapeutically DHEA might be useful for improving psychological well-being in the elderly, reducing disease activity in people with mild to moderate systemic lupus erythematosus and myotonic dystrophy, improving mood in those clinically depressed, and improving various parameters in women with adrenal insufficiency. Although many other claims have been made for DHEA in diverse conditions, such as aging, dementia, and AIDS, no well-designed clinical trials have clearly substantiated the utility and safety of long-term DHEA supplementation.     

Changes in ovarian morphology and serum hormones in the rat after treatment with dehydroepiandrosterone.

This investigation was designed to study ovarian and hormonal changes in the rat after treatment with dehydroeplandrosterone (DHEA). We identified a heterogeneous experimental group of animals with respect to ovarian histology: group I, corpora lutea (Cls) + cysts; group II, CLs + no cysts; group III, no CLs + cysts; group IV, no CLs + no cysts. Histological sections of these ovaries showed healthy and atretic follicles in different stages of cytomorphosis and degeneration. The aforementioned histological groups were also heterogeneous according to their hormonal profiles. Serum androgens, estrogens, and prolactin concentrations are significantly increased in DHEA-treated animals as compared with controls. There was no significant difference in follicle stimulating hormone between rats with cysts and rats without cysts after DHEA treatment. After 20 days of DHEA treatment, rats with CLs have very high levels of luteinizing hormone. Luteinizing hormone and prolactin levels are significantly higher in rats with cysts than in rats without cysts after 10 days of DHEA treatment. As has been shown in this inquiry, androgens and estradiol levels in rats with cysts after DHEA treatment are higher than those in rats without cysts after DHEA treatment. Therefore, this study suggests that the ovarian cystic condition developed after DHEA treatment in rats, is associated with higher levels of circulating androgens, estradiol, and prolactin.     

Changes in ovarian morphology and serum hormones in the rat after treatment with dehydroepiandrosterone

This investigation was designed to study ovarian and hormonal changes in the after treatment with dehydroeplandrosterone (DHEA). We identified a heterogeneous experimental group of animals with respect to ovarian histology: group I, corpora lutea (Cls) + cysts; group II, CLs + no cysts; group III, no CLs + cysts; group IV, no CLs + no cysts. Histological sections of these ovaries showed healthy and atretic follicles in different stages of cytomorphosis and degeneration. The aforementioned histological groups were also heterogeneous according to their hormonal profiles. Serum androgens, estrogens, and prolactin concentrations are significantly increased in DHEA-treated animals as compared with controls. There was no significant difference in follicle stimulating hormone between the with cysts and rats without cysts after DHEA treatment. After 20 days of DHEA treatment, rats with CLs have very high levels of luteinizing hormone. Luteinizing hormone and prolactin levels are significantly higher in rats with cysts than in rats without cysts after 10 days of DHEA treatment. As has been shwon in this inquiry, androgens and estradiol levels in rats with cysts after DHEA treatment are higher than those in rats without cysts after DHEA treatment. Therefore, this study suggests that the ovarian cystic condition developed after DHEA treatment in rats, is associated with higher levels of circulating androgens, estradiol, and prolactin.     

Neuroendocrine effect of a short-term treatment with DHEA in postmenopausal women

Objectives: A progressive decline of plasma dehydroepiandrosterone (DHEA) levels occurs in women during aging related to the reduction of adrenocortical secretion. A specific action of DHEA on the central nervous system (CNS) is suggested by the improvement of psychological and physical well-being in postmenopausal women after DHEA supplementation. The aim of the present study was to investigate the neuroendocrine effects of short-term DHEA supplementation in postmenopausal women, evaluating changes of plasma β-endorphin (β-EP) and growth hormone (GH) before and after oral DHEA (100 mg/day) for 7 days in postmenopausal women (n=6). Methods: Before and after 7 days of DHEA supplementation, postmenopausal women underwent a neuroendocrine test with clonidine, an 2 presinaptic agonist for adrenergic system, (1.25 mg i.v.). Basal plasma DHEA, androstenedione (A), testosterone (T), estrone (E₁) and estradiol (E₂) levels were evaluated before and after treatment, while plasma β-EP and GH levels were measured before and 15, 30, 45, 60 and 90 min after clonidine injection. Results: Basal plasma β-EP and GH levels did not show a significant difference before and after short-term DHEA administration, while circulating A, T, E₁ and E₂ significantly increased after treatment. The clonidine test induced a significant increase of plasma β-EP levels in women after receiving DHEA supplementation but not before; conversely, plasma GH levels increased both before and after treatment. Conclusions: The present study indicates that short-term DHEA supplementation in postmenopausal women is able to restore the impaired response of pituitary β-EP to clonidine, an 2 presinaptic agonist. According to these data it is possible to hypothesize that DHEA could play a role in the psychological and physical well-being of postmenopausal women acting via a restoration of neuroendocrine control of antero-pituitary β-EP secretion.     

DHEA as a miracle drug in the treatment of poor responders; hype or hope?

Dehydroepiandrosterone (DHEA) is being presented as a miracle-drug for the treatment of women responding poorly to gonadotrophin stimulation, while the debate on its actual effectiveness is still ongoing. We would like to present how insufficient the current evidence of acceptable quality is to warrant a conclusion that DHEA supplementation is an effective treatment for women with diminished ovarian reserve. We believe that large-scale, well-designed confirmatory studies are necessary to prove the efficacy of DHEA before it can be recommended for routine use.     

脱氢表雄酮可以改善卵巢低反应患者的体外受精结局

目的探讨卵巢低反应患者补充脱氢表雄酮（DHEA）后卵巢储备指标及体外受精结局的变化。方法纳入50名前次IVF—ET治疗失败,证明是卵巢低反应,并再次要求IVF—ET治疗的患者。采用前瞻性单因素自身对照研究。入选患者接受DHEA75mg／日,至少治疗3个月后,每个患者采用与前一周期相同的卵巢刺激方案和FSH起始剂量促排卵。比较DHEA治疗前后,月经周期第三天AFC数量、FSH、抑制素B、抗苗勒氏管激素水平等卵巢储备指标;比较前后周期血清雌二醇（E2）峰值、HCG日〉15mm卵泡数量、回收卵母细胞和MII卵母细胞的数量、胚胎的数量和质量等治疗反应指标;比较治疗前后,临床妊娠率、流产率、活产率等体外受精周期结局差异。结果50例患者DHEA治疗前后AFC数量显著增加（P〈0．05）,月经第3天FSH、抑制素B和抗苗勒氏管激素水平无明显改变（P〉0．05）;补充DHEA后,卵巢刺激反应得到了显著改善,E2峰值水平、〉15mm的卵泡数量、获卵数、MII的卵子数量均有显著增加（P〉0．05）,治疗前后受精率相似（分别为67±42％和72±30％,P〉0．05）,可移植胚胎数量显著增加,由平均数量0．85个增至2．0个（P〈0．05）,可移植胚胎的优胚率由26％增至47％,但没有统计学意义（P〉0．05）。由于反应不良取消周期的比例显著降低（P〈0．05）,使用DHEA后周期妊娠率为30％,活产率为20％。50例患者对DHEA耐受良好,无严重不良反应。结论补充DHEA后可以增加胚胎数量,改善胚胎质量,提高临床妊娠率,改善卵巢低反应体外受精结局。其改善结局的机制可能是通过减少2—10mm的窦卵泡闭锁,增加AFC途径实现的。     

The effect of dehydroepiandrosterone on Zucker rats selected for fat food preference

When allowed to select between macronutrients in a 1-h-a-day meal paradigm, Zucker rats consume 20–80% of their total caloric intake as fat. If they receive an intraperitoneal injection of DHEA 2 h before such a test meal, they consume fewer total calories. The magnitude of this effect on each macronutrient depends upon the animal's initial preference for fat; the higher the initial fat preference, the more profound is the decrease in caloric intake and the more pronounced the effect on fat consumption. Doses as low as 25 mg DHEA/kg body weight are effective. Lean Zucker rats that prefer to consume a high-fat diet have higher epinephrine and dopamine levels in select regions of the hypothalamus known to control food intake. Administration of DHEA to such animals 2 h before decapitation reduces the content of norepinephrine and these monoamines to levels that mimic the values found in the low-fat-preferring animals. It is hypothesized that exogenous DHEA causes the acute release of norepinephrine, epinephrine, and dopamine in select regions of the hypothalamus, and this release causes a decrease in food intake, particularly fat.     

Asthma and Dehydroepiandrosterone (DHEA): Facts and Hypotheses

Dehydroepiandrosterone (DHEA) is considered as an important immunomodulating and anti-inflammatory hormone. Despite the continuing interest in DHEA replacement therapy, our knowledge of its effects upon asthma is very limited. DHEA is able to reverse cytokine imbalances associated with asthma, may prevent and attenuate allergic inflammation in airways, and does not possess the undesirable side effects of glucocorticoids; therefore, it may be potentially applied in the treatment of asthma. The steroid-sparing effect observed with DHEA clinically could appear especially favorable in asthmatic patients receiving oral treatment and those inhaling high doses of glucocorticoids. In addition, DHEA and its analogs might prove useful in reversing relative glucocorticoids insensitivity in patients with corticosteroid-resistant asthma. In this review we have focused specifically on DHEA’s role in asthma.     

Dehydroepiandrosterone-dependent induction of peroxisomal proliferation can be reduced by aspartyl esterification without attenuation of inhibitory bone loss in ovariectomy animal model

The purpose of this study was to determine whether esterification of dehydroepiandrosterone with aspartate (DHEA-aspartate) could reduce peroxisomal proliferation induced by DHEA itself, without loss of antiosteoporotic activity. Female Sprague-Dawley rats were ovariectomized, then DHEA or DHEA-aspartate was administered intraperitoneally at 0.34 mmol/kg BW 3 times a week for 8 weeks. DHEA-aspartate treatment in ovariectomized rats significantly increased trabeculae area in tibia as much as DHEA treatment. Urinary Ca excretion was not significantly increased by DHEA or DHEA-aspartate treatment in ovariectomized rats, while it was significantly increased by ovariectomy. Osteocalcin concentration and alkaline phosphatase activity in serum and cross linked N-telopeptide type I collagen level in urine were not significantly different between DHEA-aspartate and DHEA treated groups. DHEA-aspartate treatment significantly reduced liver weight and hepatic palmitoyl-coA oxidase activity compared to DHEA treatment. DHEA-aspartate treatment maintained a nearly normal morphology of peroxisomes, while DHEA treatment increased the number and size of peroxisomes in the liver. According to these results, it is concluded that DHEA-aspartate ester has an inhibitory effect on bone loss in ovariectomized rats with a marked reduction of hepatomegaly and peroxisomal proliferation compared to DHEA.     

Effects of dietary dehydroepiandrosterone on food intake and body weight in rats with medial hypothalamic knife cuts

Dehydroepiandrosterone (DHEA) is a steroid which has been reported to have anti-obesity effects when added to the diets of rats and mice. In this report, rats made hyperphagic with medial hypothalamic knife cuts were placed on a diet containing 0.45% DHEA or a control diet. Knife cut rats on the control diet ate more food and gained more weight than sham-operated rats on the control diet. In contrast, knife cut rats fed the DHEA diet weighed the same as shams on the DHEA diet and were only observed to be hyperphagic on one of eight 24 hour measurements taken during a five week period. Dietary DHEA reduced food intake and body weight of both knife cut and sham-operated rats, though the effects were smaller in shams. As these effects of DHEA were reminiscent of the effects of dietary quinine adulteration on intake by knife cut rats, a second experiment measured the food intake of unoperated rats when given a choice between a control high-fat diet and one adulterated with various concentrations of DHEA. Even at a concentration of 0.05%, rats clearly identified and avoided the DHEA-adulterated diet. While these results do not rule out effects of DHEA on metabolic rate or lipogenesis, they do indicate that the unpalatability of DHEA-adulterated diets may be a contributing factor in the observed effects on food intake and body weight.     

Effects of beta‐hydroxy‐beta‐methylbutyrate supplementation on skeletal muscle in healthy and cirrhotic rats

Beta‐hydroxy‐beta‐methylbutyrate (HMB) is a leucine metabolite with protein anabolic effects. We examined the effects of an HMB‐enriched diet in healthy rats and rats with liver cirrhosis induced by multiple doses of carbon tetrachloride (CCl4). HMB increased branched‐chain amino acids (BCAAs; valine, leucine and isoleucine) in blood and BCAA and ATP in muscles of healthy animals. The effect on muscle mass and protein content was insignificant. In CCl4‐treated animals alterations characteristic of liver cirrhosis were found with decreased ratio of the BCAA to aromatic amino acids in blood and lower muscle mass and ATP content when compared with controls. In CCl4‐treated animals consuming HMB, we observed higher mortality, lower body weight, higher BCAA levels in blood plasma, higher ATP content in muscles, and lower ATP content and higher cathepsin B and L activities in the liver when compared with CCl4‐treated animals without HMB. We conclude that (1) HMB supplementation has a positive effect on muscle mitochondrial function and enhances BCAA concentrations in healthy animals and (2) the effects of HMB on the course of liver cirrhosis in CCl4‐treated rats are detrimental. Further studies examining the effects of HMB in other models of hepatic injury are needed to determine pros and cons of HMB in the treatment of subjects with liver cirrhosis.     

Synergistic anorectic effect of dehydroepiandrosterone and d-Fenfluramine on the obese Zucker rat.

Fasted obese, female Zucker rats accustomed to eating a single high fat meal within 1 h a day were treated with intraperitoneal injections of dehydroepiandrosterone (DHEA) and dextrofenfluramine (d-fen), either individually or in combination. Caloric intake was measured over a 1-h period 2 h after drug administration, and results compared to that of vehicle-treated controls. At 50 mg/kg body weight, DHEA did not affect food intake. At doses of < or = 2 mg/kg d-fen did not affect food intake. Together, however, DHEA 50 mg/kg and d-fen < or = 2 mg/kg significantly decreased food intake. At doses of > or = 3 mg/kg d-fen diminished caloric intake by itself, and the addition of DHEA significantly augmented this effect. Neurotransmitter levels in select regions of the hypothalamus of animals treated using a similar drug protocol showed several changes in the levels of serotonin and its metabolite 5 hydroxyindole acetic acid (5-HIAA). It is hypothesized that DHEA augments the production of serotonin while d-fenfluramine enhances its release, and together these two actions may account for the synergistic action of DHEA and d-fenfluramine.     

Synergistic effects of dehydroepiandrosterone and fluoxetine on proliferation of progenitor cells in the dentate gyrus of the adult male rat

The 5-HT re-uptake inhibitor (SSRI) fluoxetine and the adrenal hormone dehydroepiandrosterone (DHEA) both increase the proliferation of progenitor cells in the adult hippocampus and also have antidepressant activity. This paper explores the combined ability of fluoxetine and DHEA to affect this process in the dentate gyrus of adult rats. We show that DHEA can render an otherwise ineffective dose of fluoxetine (2.5 mg/kg) able to increase progenitor cell proliferation to the same extent as doses four times higher (10 mg/kg). This synergistic action does not appear to be mediated by alterations in brain-derived neurotrophic factor (BDNF) gene expression; or by TrkB, mineralocorticoid, glucocorticoid, or 5-HT (5HT1A) receptor expression in the dentate gyrus; or by altered levels of plasma corticosterone. In a second experiment, the synergism between DHEA and fluoxetine was replicated. Furthermore, flattening the diurnal rhythm of plasma corticosterone by implanting additional corticosterone pellets s.c. prevented the effect of fluoxetine on progenitor cell division. This was not overcome by simultaneous treatment with DHEA, despite the latter's reported anti-glucocorticoid actions. The cellular mechanism for the potentiating action of DHEA on the pro- proliferative effects of fluoxetine in the adult hippocampus remains to be revealed. Since altered neurogenesis has been linked to the onset or recovery from depression, one consequence of these results is to suggest DHEA as a useful adjunct therapy for depression.     

Effect of acute DHEA administration on free testosterone in middle-aged and young men following high-intensity interval training

With advancing age, plasma testosterone levels decline, with free testosterone levels declining more significantly than total testosterone. This fall is thought to underlie the development of physical and mental weakness that occurs with advancing age. In addition, vigorous exercise can also lower total and free testosterone levels with the decline greatest in physically untrained men. The purpose of the study was to evaluate the effect of oral DHEA supplementation, a testosterone precursor, on free testosterone in sedentary middle-aged men during recovery from a high-intensity interval training (HIIT) bout of exercise. A randomized, double-blind, placebo-controlled crossover study was conducted for 8 middle-aged participants (aged 49.3 ± 2.4 years) and an additional 8 young control participants (aged 21.4 ± 0.3 years). Each participant received DHEA (50 mg) and placebo on separate occasions one night (12 h) before a 5-session, 2-min cycling exercise (100 % $\dot{V} {\rm O}_{2{\rm max}}$ ). While no significant age difference in total testosterone was found, middle-aged participants exhibited significantly lower free testosterone and greater luteinizing hormone (LH) levels than the young control group. Oral DHEA supplementation increased circulating DHEA-S and free testosterone levels well above baseline in the middle-aged group, with no significant effect on total testosterone levels. Total testosterone and DHEA-S dropped significantly until 24 h after HIIT for both age groups, while free testosterone of DHEA-supplemented middle-aged men remained unaffected. These results demonstrate acute oral DHEA supplementation can elevate free testosterone levels in middle-aged men and prevent it from declining during HIIT. Therefore, DHEA supplementation may have significant benefits related to HIIT adaptation.     

Induction and modulation of hepatic preneoplasia and neoplasia in the rat by dehydroepiandrosterone

Dehydroepiandrosterone (DHEA), the main adrenal steroid in humans and a precursor in androgen and estrogen biosynthesis, acts as a peroxisome proliferator and as a hepatocarcinogen in rats. Neoplasms emerge from a glycogenotic/amphophilic/basophilic preneoplastic cell lineage. A higher female tumor incidence suggests a relevant influence of sex hormones. DHEA enhances hepatocarcinogenesis induced by N-nitrosomorpholine (NNM), which is characterized by the glycogenotic/basophilic cell lineage. The tumor promoting effect is related to an additional amphophilic/basophilic preneoplastic lesion sequence and to faster proliferation of the basophilic preneoplastic lesions. Nevertheless, hepatocellular carcinomas provided under DHEA treatment seem to have a less malignant phenotype compared to tumors induced by NNM only. Further, DHEA treatment reduces growth and generation of glycogen storage foci (GSF) in initial NNM-treated rats. Thus, DHEA treatment results in both, a growth stimulation of the late basophilic lesion type with an additional amphophilic lesion sequence, and in a growth inhibition of early preneoplastic lesions, addressing especially GSF. DHEA also inhibits the growth of physiologically proliferating liver tissue. This might be explained by a DHEA related cellular metabolism, which results in significant energy consumption. Additionally, a DHEA-induced alteration of cytokine levels might contribute to this growth inhibition as well.     

Dehydroepiandrosterone-mediated decrease in caloric intake by obese Zucker rats is not due to changes in serum entrostatin-like immunoreactivity

To understand the mechanism(s) of appetite modulation by DHEA, we have undertaken a series of studies to examine the effects of DHEA on neurotransmitters and neuropeptides known to affect appetitive behavior. Here, we report the effect of DHEA on serum enterostatin-VPDPR or E, a pentapeptide known to cause selective diminution in fat intake. Four-week-old lean (fa/+) and obese (fa/fa) Zucker rats were divided into control and treatment groups. DHEA-treated groups received powdered chow containing 0.6% DHEA ad lib for 16 weeks. Another group of obese rats was pair fed to match the intake of the obese DHEA-treated rats. At the end of this period, trunk blood was collected from fasted rats for assay of E-like immunoreactivity (E-LI) by ELISA. DHEA treatment caused a significant diminution in circulating E-LI in both lean (control: 2030 +/- 226; treated: 752 +/- 145 ng/mL; n = 10, p < 0.0001) and obese (control: 2489 +/- 391, n = 6; treated: 1123 +/- 185 ng/mL, n = 7; p = 0.0003) rats. Because DHEA treatment decreases caloric intake and body weight, we examined the effect of caloric intake and body weight on E-LI levels. Serum ELI levels were lower in the obese DHEA-treated group compared to that of obese pair fed (pair fed: 1589 +/- 313, n = 6; DHEA: 1123 +/- 185 ng/mL, n = 7), but the differences were statistically insignificant (p = 0.185). Also, both weight-matched lean and obese control rats had significantly (p < 0.008) higher E-LI than their DHEA-treated counterparts. To examine whether the decrease in serum E-LI following DHEA treatment could be due to increased peptide metabolism, the rate of disappearance of endogenous E-LI from serum (obese control and DHEA-treated) at 37 degrees C was evaluated. The results show an attenuation of peptide metabolism in serum from DHEA-treated rats, a finding contrary to our expectations. In summary, DHEA treatment lowers serum E-LI levels both in lean and obese Zucker rats. This decrement in peptide level is not secondary to changes in body weight or caloric intake due to DHEA, or due to altered serum peptide metabolism. Although DHEA appears to be a potent modulator of E-LI levels, the relationship between DHEA and E-LI in relation to appetitive behavior remains to be clarified.