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1.
Mini Rev Med Chem ; 23(8): 941-952, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36121077

RESUMO

Dehydroepiandrosterone (DHEA) is the most abundant steroid hormone in primates, which is predominantly synthesized in the adrenal cortex. A characteristic curve of growth and decline of its synthesis during life was observed, together with the corresponding formation of its sulphate ester (DHEAS). High levels of plasma circulating DHEA are suggested as a marker of human longevity, and various pathophysiological conditions lead to a decreased DHEA level, including adrenal insufficiency, severe systemic diseases, acute stress, and anorexia. More recent studies have established the importance of DHEA in the central nervous system (CNS). A specific intranuclear receptor for DHEA has not yet been identified; however, highly specific membrane receptors have been detected in endothelial cells, the heart, kidney, liver, and the brain. Research shows that DHEA and DHEAS, as well as their metabolites, have a wide range of effects on numerous organs and organ systems, which places them in the group of potential pharmacological agents useful in various clinical entities. Their action as neurosteroids is especially interesting due to potential neuroprotective, pro-cognitive, anxiolytic, and antidepressant effects. Evidence from clinical studies supports the use of DHEA in hypoadrenal individuals and in treating depression and associated cognitive disorders. However, there is also an increasing trend of recreational DHEA misuse in healthy people, as it is classified as a dietary supplement in some countries. This article aims to provide a critical review regarding the biological and pharmacological effects of DHEA, its mechanism of action, and potential therapeutic use, especially in CNS disorders.


Assuntos
Desidroepiandrosterona , Células Endoteliais , Animais , Humanos , Desidroepiandrosterona/farmacologia , Desidroepiandrosterona/uso terapêutico , Células Endoteliais/metabolismo , Sulfato de Desidroepiandrosterona/metabolismo , Sulfato de Desidroepiandrosterona/farmacologia , Encéfalo/metabolismo , Esteroides
2.
Front Endocrinol (Lausanne) ; 13: 892270, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35733782

RESUMO

Dehydroepiandrosterone (DHEA) is an androgen synthesized by the adrenal cortex, which is an intermediary in the biosynthesis of sex hormones, such as testosterone and estradiol. DHEA mostly circulates as a conjugated ester, in the form of sulfate (DHEA-S). There exist several endogenous factors able to influence its synthesis, the most common ones being the corticotrophin-releasing hormone (CRH), adrenocorticotrophin (ACTH), growth factors, and proinflammatory cytokines, among others. Like other steroid hormones, DHEA, can alter the functioning of immune cells and therefore the course of diseases exhibiting an immune-inflammatory component, mostly from autoimmune or infectious nature. We herein review the role played by DHEA during a major infectious disease like tuberculosis (TB). Data recorded from TB patients, mouse models, or in vitro studies show that DHEA is likely to be implied in better disease control. This provides a stimulating background for carrying out clinical studies aimed at assessing the usefulness of DHEA as an adjuvant in TB patients.


Assuntos
Córtex Suprarrenal , Tuberculose , Córtex Suprarrenal/metabolismo , Hormônio Adrenocorticotrópico/metabolismo , Androgênios/metabolismo , Animais , Sulfato de Desidroepiandrosterona/metabolismo , Humanos , Camundongos , Tuberculose/tratamento farmacológico
3.
PLoS One ; 16(12): e0261570, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34929017

RESUMO

Previous studies targeting inter-individual differences in pain processing in migraine mainly focused on the perception of pain. Our main aim was to disentangle pain anticipation and perception using a classical fear conditioning task, and investigate how migraine frequency and pre-scan cortisol-to-dehydroepiandrosterone sulfate (DHEA-S) ratio as an index of neurobiological stress response would relate to neural activation in these two phases. Functional Magnetic Resonance Imaging (fMRI) data of 23 participants (18 females; mean age: 27.61± 5.36) with episodic migraine without aura were analysed. We found that migraine frequency was significantly associated with pain anticipation in brain regions comprising the midcingulate and caudate, whereas pre-scan cortisol-to DHEA-S ratio was related to pain perception in the pre-supplementary motor area (pre-SMA). Both results suggest exaggerated preparatory responses to pain or more general to stressors, which may contribute to the allostatic load caused by stressors and migraine attacks on the brain.


Assuntos
Sulfato de Desidroepiandrosterona/metabolismo , Hidrocortisona/metabolismo , Transtornos de Enxaqueca/psicologia , Percepção da Dor , Adulto , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Química Encefálica , Sulfato de Desidroepiandrosterona/análise , Feminino , Neuroimagem Funcional , Humanos , Hidrocortisona/análise , Individualidade , Imageamento por Ressonância Magnética , Masculino , Transtornos de Enxaqueca/epidemiologia , Adulto Jovem
4.
Endocr Regul ; 55(3): 174-181, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34523302

RESUMO

The pathophysiology of COVID comprises an exaggerated pro-inflammatory response. Hypothalamic-pituitary-adrenal (HPA) axis has a crucial role in various inflammatory conditions and modulated immunological response. Limited evidence is available regarding the incidence and the effect of HPA dysfunction in COVID-19. Although the cortisol levels have only been estimated in a few studies, the dehydroepiandrosterone sulfate (DHEAS) release from the adrenal gland has not been explored yet. In this mini review, the authors discuss the role of dehydroepiandrosterone (DHEA) and DHEAS in the acute stress response and immunological modulation. Various effects of DHEAS have been demonstrated in different diseases. The specific inhibitory effect of DHEA on interleukin 6 (IL-6) could be of paramount importance in COVID-19. Further, DHEA supplementation has already been proposed in inflammatory conditions, like rheumatoid arthritis. DHEAS levels in COVID-19 may help to understand the HPA axis dysfunction as well as the possibility of repurposing DHEA as a drug for mitigating the pro-inflammatory COVID-19.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19 , Sulfato de Desidroepiandrosterona/metabolismo , Desidroepiandrosterona/uso terapêutico , Sistema Hipotálamo-Hipofisário , Fatores Imunológicos/uso terapêutico , COVID-19/diagnóstico , COVID-19/imunologia , COVID-19/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/imunologia , Sistema Hipotálamo-Hipofisário/metabolismo
5.
Eur J Nutr ; 59(2): 433-450, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31256251

RESUMO

INTRODUCTION: Polycystic ovary syndrome (PCOS) is among the most prevalent endocrine disorders in women and can lead to many other disorders and chronic diseases. Thus, early diagnosis and treatment of this syndrome is important. Using probiotics, prebiotics, and synbiotics supplementations to treat PCOS seems appropriate because of their useful effects and low complications. AIMS: To assess the effects of probiotics, prebiotics, and synbiotics on hormonal indices such as testosterone, dehydroepiandrosterone sulfate (DHEA-S), sex hormone binding globulin, Free Androgen Index (FAI), and inflammatory indices, such as high sensitive C reactive protein (hsCRP), malondialdehyde (MDA), total glutathione (GSH), nitric oxide (NO), and total antioxidant capacity (TAC) as the primary outcomes and the hirsutism score as the secondary outcome. METHODS: All published articles from the beginning until 10 November 2018 in English (Cochrane Library, Web of Sciences, Google Scholar, PubMed, Scopus, and ProQuest) and Persian (SID and Magiran) databases were searched. The effect of interventions on the outcomes was reported with a standard mean difference (SMD) and confidence interval of 95%. In case of high heterogeneity, the random effect model was used instead of the fixed effect model. The statistical heterogeneity of the included clinical trials was tested using the Chi square test and I2. RESULTS: Thirteen studies with 855 participants with PCOS(438 women in the intervention group and 417 women in the control group) were included in the meta-analysis. Results of the meta-analysis showed that the SHBG (SMD: 0.56; 95% CI 0.26-0.86; P = 0.0002) and NO (SMD: 0.38; 95% CI 0.09-0.68; P = 0.01) concentration increased significantly in the probiotics and synbiotics groups compared to the placebo group. FAI (SMD: - 0.58; 95% CI - 0.95 to - 0.21; P = 0.002) and MDA (SMD: - 0.76; 95% CI - 1.46 to - 0.05; P = 0.03) concentration in the probiotics and synbiotics groups reduced significantly compared to the placebo group. The results of meta-analyses on other hormonal and inflammatory indices such as testosterone, DHEAS, GSH, hsCRP, TAC, and hirsutism score showed that there were no significant differences between the intervention and control groups. CONCLUSION: Using synbiotics and probiotics in women with polycystic ovary syndrome improve hormonal (FAI, SHBG) and inflammatory (NO, MDA) indices in these patients.


Assuntos
Hormônios/metabolismo , Inflamação/tratamento farmacológico , Síndrome do Ovário Policístico/tratamento farmacológico , Prebióticos/administração & dosagem , Probióticos/farmacologia , Simbióticos/administração & dosagem , Androgênios/metabolismo , Sulfato de Desidroepiandrosterona/metabolismo , Feminino , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/metabolismo , Probióticos/administração & dosagem , Globulina de Ligação a Hormônio Sexual/efeitos dos fármacos , Globulina de Ligação a Hormônio Sexual/metabolismo , Testosterona/metabolismo
6.
Medicine (Baltimore) ; 98(37): e17186, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517876

RESUMO

BACKGROUND: Ashwagandha (Withania somnifera (L.) Dunal) is a herb traditionally used to reduce stress and enhance wellbeing. The aim of this study was to investigate its anxiolytic effects on adults with self-reported high stress and to examine potential mechanisms associated with its therapeutic effects. METHODS: In this 60-day, randomized, double-blind, placebo-controlled study the stress-relieving and pharmacological activity of an ashwagandha extract was investigated in stressed, healthy adults. Sixty adults were randomly allocated to take either a placebo or 240 mg of a standardized ashwagandha extract (Shoden) once daily. Outcomes were measured using the Hamilton Anxiety Rating Scale (HAM-A), Depression, Anxiety, and Stress Scale -21 (DASS-21), and hormonal changes in cortisol, dehydroepiandrosterone-sulphate (DHEA-S), and testosterone. RESULTS: All participants completed the trial with no adverse events reported. In comparison with the placebo, ashwagandha supplementation was associated with a statistically significant reduction in the HAM-A (P = .040) and a near-significant reduction in the DASS-21 (P = .096). Ashwagandha intake was also associated with greater reductions in morning cortisol (P < .001), and DHEA-S (P = .004) compared with the placebo. Testosterone levels increased in males (P = .038) but not females (P = .989) over time, although this change was not statistically significant compared with the placebo (P = .158). CONCLUSIONS: These findings suggest that ashwagandha's stress-relieving effects may occur via its moderating effect on the hypothalamus-pituitary-adrenal axis. However, further investigation utilizing larger sample sizes, diverse clinical and cultural populations, and varying treatment dosages are needed to substantiate these findings. TRIAL REGISTRATION: Clinical Trials Registry-India (CTRI registration number: CTRI/2017/08/009449; date of registration 22/08/2017).


Assuntos
Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Estresse Psicológico/tratamento farmacológico , Adulto , Ansiolíticos/efeitos adversos , Ansiedade/metabolismo , Sulfato de Desidroepiandrosterona/metabolismo , Método Duplo-Cego , Feminino , Humanos , Hidrocortisona/metabolismo , Masculino , Fitoterapia , Extratos Vegetais/efeitos adversos , Estresse Psicológico/metabolismo , Testosterona/metabolismo , Resultado do Tratamento
7.
Oxid Med Cell Longev ; 2018: 5758191, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30228856

RESUMO

Tribulus terrestris (TT) has been considered as a potential stimulator of testosterone production, which has been related with steroidal saponins prevailing in this plant. Cyclophosphamide (CP) is the most commonly used anticancer and immunosuppressant drug, which causes several toxic effects, especially on the reproductive system. Patients who need to use CP therapy exhibit reduced fertility or infertility, which impacts both physically and emotionally on the decision to use this drug, especially among young men. We hypothesized that the treatment with TT dry extract would protect the male reproductive system against CP toxicity. Mice received dry extract of TT (11 mg/kg) or vehicle by gavage for 14 days. Saline or CP was injected intraperitoneally at a single dose (100 mg/kg) on the 14th day. Animals were euthanized 24 h after CP administration, and testes and epididymis were removed for biochemical and histopathological analysis and sperm evaluation. The dry extract of TT was evaluated by HPLC analysis and demonstrated the presence of protodioscin (1.48%, w/w). CP exposure increased lipid peroxidation, reactive species, and protein carbonylation and altered antioxidant enzymes (SOD, CAT, GPx, GST, and GR). Moreover, acute exposure to CP caused a reduction on 17 ß-HSD activity, which may be related to the reduction in serum testosterone levels, histopathological changes observed in the testes, and the quality of the semen. The present study highlighted the role of TT dry extract to ameliorate the alterations induced by CP administration in mice testes, probably due to the presence of protodioscin.


Assuntos
Ciclofosfamida/efeitos adversos , Substâncias Protetoras/farmacologia , Reprodução/efeitos dos fármacos , Tribulus/química , 17-Hidroxiesteroide Desidrogenases/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Sulfato de Desidroepiandrosterona/metabolismo , Diosgenina/análogos & derivados , Diosgenina/análise , Masculino , Camundongos , Extratos Vegetais/farmacologia , Padrões de Referência , Saponinas/análise , Sêmen/metabolismo , Túbulos Seminíferos/efeitos dos fármacos , Túbulos Seminíferos/patologia , Espermatozoides/efeitos dos fármacos , Espermatozoides/metabolismo , Testosterona/sangue
8.
Vitam Horm ; 108: 223-250, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30029728

RESUMO

Steroid hormones form an integral part of normal development in mammalian organisms. Cholesterol is the parent compound from which all steroid hormones are synthesized. The product pregnenolone formed from cholesterol serves as precursor for mineralocorticoids, glucocorticoids, as well as dehydroepiandrosterone (DHEA) and its derived sexual hormones. DHEA assumes the prohormone status of a predominant endogenous precursor and a metabolic intermediate in ovarian follicular steroidogenesis. DHEA supplementation has been used to enhance ovarian reserve. Steroids like estradiol and testosterone have long been contemplated to play important roles in regulating meiotic maturation of oocytes in conjunction with gonadotropins. It is known that oocyte priming with estrogen is necessary to develop calcium (Ca2+) oscillations during maturation. Accruing evidence from diverse studies suggests that DHEA and its sulfate (dehydroepiandrosterone sulfate, DHEA-S) play significantly vital role not only as intermediates in androgen and estrogen formation, but may also be the probable 'oocyte factor' and behave as endogenous agonists triggering calcium oscillations for oocyte activation. DHEA/DHEA-S have been reported to regulate calcium channels for the passage of Ca2+ through the oocyte cytoplasm and for maintaining required threshold of Ca2+ oscillations. This role of DHEA/DHEA-S assumes critical significance in assisted reproductive technology and in-vitro fertilization treatment cycles where physical, chemical, and mechanical methods are employed for artificial oocyte activation to enhance fertilization rates. However, since these methods are invasive and may also cause adverse epigenetic modifications; oral or culture-media supplementation with DHEA/DHEA-S provides a noninvasive innate mechanism of in-vitro oocyte activation based on physiological metabolic pathway.


Assuntos
Sulfato de Desidroepiandrosterona/metabolismo , Desidroepiandrosterona/metabolismo , Mamíferos/fisiologia , Animais , Humanos , Oócitos/fisiologia , Interações Espermatozoide-Óvulo , Esteroides/metabolismo
9.
Artigo em Inglês | MEDLINE | ID: mdl-27387253

RESUMO

Androgen excess (AE) is a key feature of polycystic ovary syndrome (PCOS) and results in, or contributes to, the clinical phenotype of these patients. Although AE will contribute to the ovulatory and menstrual dysfunction of these patients, the most recognizable sign of AE includes hirsutism, acne, and androgenic alopecia or female pattern hair loss (FPHL). Evaluation includes not only scoring facial and body terminal hair growth using the modified Ferriman-Gallwey method but also recording and possibly scoring acne and alopecia. Moreover, assessment of biochemical hyperandrogenism is necessary, particularly in patients with unclear or absent hirsutism, and will include assessing total and free testosterone (T), and possibly dehydroepiandrosterone sulfate (DHEAS) and androstenedione, although these latter contribute limitedly to the diagnosis. Assessment of T requires use of the highest quality assays available, generally radioimmunoassays with extraction and chromatography or mass spectrometry preceded by liquid or gas chromatography. Management of clinical hyperandrogenism involves primarily either androgen suppression, with a hormonal combination contraceptive, or androgen blockade, as with an androgen receptor blocker or a 5α-reductase inhibitor, or a combination of the two. Medical treatment should be combined with cosmetic treatment including topical eflornithine hydrochloride and short-term (shaving, chemical depilation, plucking, threading, waxing, and bleaching) and long-term (electrolysis, laser therapy, and intense pulse light therapy) cosmetic treatments. Generally, acne responds to therapy relatively rapidly, whereas hirsutism is slower to respond, with improvements observed as early as 3 months, but routinely only after 6 or 8 months of therapy. Finally, FPHL is the slowest to respond to therapy, if it will at all, and it may take 12 to 18 months of therapy for an observable response.


Assuntos
Acne Vulgar/metabolismo , Alopecia/metabolismo , Androstenodiona/metabolismo , Sulfato de Desidroepiandrosterona/metabolismo , Hirsutismo/metabolismo , Hiperandrogenismo/metabolismo , Síndrome do Ovário Policístico/metabolismo , Testosterona/metabolismo , Inibidores de 5-alfa Redutase/uso terapêutico , Acne Vulgar/tratamento farmacológico , Acne Vulgar/etiologia , Alopecia/tratamento farmacológico , Alopecia/etiologia , Antagonistas de Androgênios/uso terapêutico , Anticoncepcionais Orais Combinados/uso terapêutico , Anticoncepcionais Orais Hormonais/uso terapêutico , Eflornitina/uso terapêutico , Feminino , Remoção de Cabelo , Hirsutismo/tratamento farmacológico , Hirsutismo/etiologia , Humanos , Hiperandrogenismo/tratamento farmacológico , Hiperandrogenismo/etiologia , Inibidores da Ornitina Descarboxilase/uso terapêutico , Síndrome do Ovário Policístico/complicações
10.
Mol Cell Endocrinol ; 428: 133-41, 2016 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-27033324

RESUMO

The sodium-dependent organic anion transporter SOAT specifically transports sulfated steroid hormones and is supposed to play a role in testicular steroid regulation and male fertility. The present study aimed to identify novel specific SOAT inhibitors for further in vitro and in vivo studies on SOAT function. More than 100 compounds of different molecular structures were screened for inhibition of the SOAT-mediated transport of dehydroepiandrosterone sulfate in stably transfected SOAT-HEK293 cells. Twenty-five of these with IC50 values covering four orders of magnitude were selected as training set for 3D pharmacophore modelling. The SOAT pharmacophore features were calculated by CATALYST and consist of three hydrophobic sites and two hydrogen bond acceptors. By substrate database screening, compound T 0511-1698 was predicted as a novel SOAT inhibitor with an IC50 of 15 µM. This value was confirmed by cell-based transport assays. Therefore, the developed SOAT pharmacophore model demonstrated its suitability in predicting novel SOAT inhibitors.


Assuntos
Sulfato de Desidroepiandrosterona/metabolismo , Avaliação Pré-Clínica de Medicamentos , Modelos Moleculares , Transportadores de Ânions Orgânicos/antagonistas & inibidores , Transportadores de Ânions Orgânicos/química , Relação Quantitativa Estrutura-Atividade , Ácidos e Sais Biliares/química , Ácidos e Sais Biliares/farmacologia , Células HEK293 , Humanos , Concentração Inibidora 50 , Reprodutibilidade dos Testes
11.
JAMA Oncol ; 1(4): 495-504, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26181260

RESUMO

IMPORTANCE: Statin use has been associated with improved prostate cancer outcomes. Dehydroepiandrosterone sulfate (DHEAS) is a precursor of testosterone and a substrate for SLCO2B1, an organic anionic transporter. We previously demonstrated that genetic variants of SLCO2B1 correlated with time to progression (TTP) during receipt of androgen deprivation therapy (ADT). Statins also use SLCO2B1 to enter cells, and thus we hypothesized that they may compete with DHEAS uptake by the tumor cells. OBJECTIVE: To evaluate whether statin use prolongs TTP during ADT for hormone-sensitive prostate cancer. DESIGN, SETTING, AND PARTICIPANTS: In vitro studies were performed using prostate cancer cell lines at an academic, comprehensive cancer center. Statin use was retrospectively analyzed in 926 patients who had received ADT for biochemical or metastatic recurrence or de novo metastatic prostate cancer between January 1996 and November 2013. MAIN OUTCOMES AND MEASURES: To determine whether statins interfere with DHEAS uptake, we performed in vitro studies using prostate cancer cell lines. Next, we queried our institutional clinical database to assess for an association between statin use and TTP during ADT using multivariable Cox regression analysis and adjusted for known prognostic factors. RESULTS: In vitro, we demonstrated that statins block DHEAS uptake by competitively binding to SLCO2B1. In our ADT cohort of 926 patients, 283 (31%) were taking a statin at ADT initiation. After a median follow-up of 5.8 years, 644 patients (70%) had experienced disease progression while receiving ADT. Median TTP during ADT was 20.3 months (95% CI, 18-24 months). Men taking statins had a longer median TTP during ADT compared with nonusers (27.5 [95% CI, 21.1-37.7] vs 17.4 [95% CI, 14.9-21.1] months; P < .001). The association remained statistically significant after adjusting for predefined prognostic factors (adjusted hazard ratio, 0.83 [95% CI, 0.69-0.99]; P = .04). The positive statin effect was observed for both patients with and without metastases (adjusted hazard ratio, 0.79 [95% CI, 0.58-1.07] for M0 disease and 0.84 [95% CI, 0.67-1.06] for M1 disease; P for interaction = .72). CONCLUSIONS AND RELEVANCE: Statin use at the time of ADT initiation was associated with a significantly longer TTP during ADT even after adjustment for known prognostic factors. Our in vitro finding that statins competitively reduce DHEAS uptake, thus effectively decreasing the available intratumoral androgen pool, affords a plausible mechanism to support the clinical observation of prolonged TTP in statin users.


Assuntos
Antagonistas de Androgênios/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Ligação Competitiva , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Distribuição de Qui-Quadrado , Sulfato de Desidroepiandrosterona/metabolismo , Progressão da Doença , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/metabolismo , Masculino , Análise Multivariada , Neoplasias Hormônio-Dependentes/genética , Neoplasias Hormônio-Dependentes/metabolismo , Neoplasias Hormônio-Dependentes/patologia , Transportadores de Ânions Orgânicos/genética , Transportadores de Ânions Orgânicos/metabolismo , Modelos de Riscos Proporcionais , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Interferência de RNA , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Transfecção , Resultado do Tratamento
12.
J Steroid Biochem Mol Biol ; 145: 206-12, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24704255

RESUMO

The dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEA-S) concentrations during acute and chronic exercise (training) have been investigated only fairly recently. DHEA is generally preferred to DHEA-S for exploring the acute exercise repercussions in laboratory or field tests because of its shorter elimination half-life. Conversely, DHEA-S is preferred to estimate chronic adaptations. Both can be measured noninvasively in saliva, and it is therefore possible to follow these hormone responses in elite athletes during competitive events and in healthy and pathological populations, without imposing additional stress. Indeed, the correlation between saliva and serum concentrations is high for steroid hormones, both at rest and during exercise. In this review, we will first summarize the current knowledge on the DHEA/DHEA-S responses to exercise and examine the potential modulating factors: exercise intensity, gender, age, and training. We will then discuss the ergogenic effects that athletes expect from the exogenous administration of DHEA and the antidoping methods of analysis currently used to detect this abuse.


Assuntos
Envelhecimento , Desidroepiandrosterona/metabolismo , Dopagem Esportivo , Exercício Físico , Fatores Etários , Atletas , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona/metabolismo , Suplementos Nutricionais , Feminino , Humanos , Masculino , Detecção do Abuso de Substâncias
13.
Endocrinology ; 154(6): 2114-28, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23554453

RESUMO

The sulfated neurosteroids pregnenolone sulfate (Δ(5)PS) and dehydroepiandrosterone sulfate (DHEAS) are known to play a role in the control of reproductive behavior. In the frog Pelophylax ridibundus, the enzyme hydroxysteroid sulfotransferase (HST), responsible for the biosynthesis of Δ(5)PS and DHEAS, is expressed in the magnocellular nucleus and the anterior preoptic area, two hypothalamic regions that are richly innervated by GnRH1-containing fibers. This observation suggests that GnRH1 may regulate the formation of sulfated neurosteroids to control sexual activity. Double labeling of frog brain slices with HST and GnRH1 antibodies revealed that GnRH1-immunoreactive fibers are located in close vicinity of HST-positive neurons. The cDNAs encoding 3 GnRH receptors (designated riGnRHR-1, -2, and -3) were cloned from the frog brain. RT-PCR analyses revealed that riGnRHR-1 is strongly expressed in the hypothalamus and the pituitary whereas riGnRHR-2 and -3 are primarily expressed in the brain. In situ hybridization histochemistry indicated that GnRHR-1 and GnRHR-3 mRNAs are particularly abundant in preoptic area and magnocellular nucleus whereas the concentration of GnRHR-2 mRNA in these 2 nuclei is much lower. Pulse-chase experiments using tritiated Δ(5)P and DHEA as steroid precursors, and 3'-phosphoadenosine 5'-phosphosulfate as a sulfonate moiety donor, showed that GnRH1 stimulates, in a dose-dependent manner, the biosynthesis of Δ(5)PS and DHEAS in frog diencephalic explants. Because Δ(5)PS and DHEAS, like GnRH, stimulate sexual activity, our data strongly suggest that some of the behavioral effects of GnRH could be mediated via the modulation of sulfated neurosteroid production.


Assuntos
Sulfato de Desidroepiandrosterona/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Hipotálamo/metabolismo , Pregnenolona/metabolismo , Sequência de Aminoácidos , Animais , Linhagem Celular , Diencéfalo/efeitos dos fármacos , Diencéfalo/metabolismo , Perfilação da Expressão Gênica , Hormônio Liberador de Gonadotropina/farmacologia , Hibridização In Situ , Masculino , Microscopia Confocal , Dados de Sequência Molecular , Neurônios/metabolismo , Hipófise/metabolismo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Ranidae , Receptores LHRH/genética , Receptores LHRH/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Homologia de Sequência de Aminoácidos , Sulfotransferases/metabolismo
14.
Ethn Dis ; 23(2): 149-54, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23530294

RESUMO

OBJECTIVES: Dehydroepiandrosterone sulfate (DHEAS) declines with age and low endogenous DHEAS concentrations have been associated with obesity. In addition, DHEAS has been studied for its role in mood and wellbeing. However, limited data are available on salivary DHEAS concentrations in African Americans. Thus, we examined age-related changes in morning salivary DHEAS and the association between DHEAS and obesity risk factors among African Americans. DESIGN: Salivary DHEAS samples (n=170) were obtained from men and women divided into three age groups: 18 to 30 (young), 31 to 45 (middle) and 46 to 60 (older) years. Anthropometric, blood glucose, high sensitivity c-reactive protein (hsCRP), and blood pressure measures were obtained. Participants completed the Center for Epidemiologic Studies Depression (CESD), Beck Depression Inventory (BDI), Daily Hassles Scale (DHS), Perceived Stress Scale (PSS) and Pittsburgh Sleep Quality Index (PSQI) scales to assess depression, daily hassles, stress and quality of sleep, respectively. RESULTS: Mean salivary DHEAS concentrations decreased significantly with increasing age: mean values were 25.8 +/- 2.4, 21.9 +/- 1.9, and 14.4 +/- .9 nmol/L for young, middle, and older groups, respectively. Like DHEAS, PSQI, DHS, CESD, MAP, WC, BMI, systolic and diastolic BP and fasting blood glucose values differed significantly in the older compared to the young and middle groups. Women had significantly lower salivary DHEAS than men (P< or =.05). CONCLUSION: The age-related decline in salivary DHEAS in African Americans is associated with cardiovascular risk factors, sleep quality, hassles and mood. Whether supplementing DHEAS levels in aging African Americans will improve health remains to be determined.


Assuntos
Negro ou Afro-Americano , Sulfato de Desidroepiandrosterona/metabolismo , Saliva/metabolismo , Adolescente , Adulto , Afeto , Fatores Etários , Glicemia/análise , Pressão Sanguínea/fisiologia , Proteína C-Reativa/análise , Depressão/etnologia , Depressão/fisiopatologia , Feminino , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Sono/fisiologia , Estresse Psicológico/fisiopatologia , Adulto Jovem
15.
Nutr J ; 11: 77, 2012 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-22995464

RESUMO

BACKGROUND: Royal jelly is a widely ingested supplement for health, but its effects on humans are not well known. The objective was to evaluate the effects of long-term royal jelly ingestion on humans. METHODS: We conducted a randomized placebo-controlled, double-blind trial. A total of 61 healthy volunteers aged 42-83 years were enrolled and were randomly divided into a royal jelly group (n = 31) and a control group (n = 30). Three thousand mg of royal jelly (RJ) or a placebo in 100 ml liquid/day were ingested for 6 months. The primary outcomes were changes in anthropometric measurements and biochemical indexes from baseline to 6 months after intervention. RESULTS: Thirty subjects in the RJ group and 26 in the control group were included in the analysis of endpoints. In an adjusted mean change of the variables from the baseline, significant differences between the two groups could be found in red blood cell counts (+0.16x106/µL for the RJ group vs. -0.01x106/µL for the control group, P = 0.0134), hematocrit (+0.9% vs. -0.8%, P = 0.0251), log (fasting plasma glucose) (+0.01 ± 0.01 log mg/dL vs. +0.05 ± 0.01 log mg/dL, P = 0.0297), log (insulinogenic index) (+0.25 vs. -0.13, P = 0.0319), log dehydroepiandrosterone sulfate (DHEA-S) (+0.08 log µg/dL vs. +0.20 log µg/dL, P = 0.0483), log testosterone (T) (+0.12 ± 0.04 log ng/mL vs. -0.02 ± 0.05 log ng/mL, P = 0.0416), log T/DHEA-S ratio (+0.05 ± 0.05 vs. -0.23 ± 0.59, P = 0.0015), and in one of the SF-36 subscale scores, mental health (MH) (+4 vs. -7, P = 0.0276). CONCLUSIONS: Six-month ingestion of RJ in humans improved erythropoiesis, glucose tolerance and mental health. Acceleration of conversion from DHEA-S to T by RJ may have been observed among these favorable effects.


Assuntos
Suplementos Nutricionais , Ácidos Graxos/administração & dosagem , Hematínicos/administração & dosagem , Resistência à Insulina , Saúde Mental , Adulto , Idoso , Idoso de 80 Anos ou mais , Androstenodiona/sangue , Androstenodiona/metabolismo , Sulfato de Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona/metabolismo , Método Duplo-Cego , Eritropoese , Feminino , Humanos , Análise de Intenção de Tratamento , Japão , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica , Fatores de Tempo
16.
Ear Hear ; 33(3): 430-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-21971082

RESUMO

OBJECTIVES: Tinnitus interferes with sleep and concentration which is associated with depression; however, no drug has been effective in treating tinnitus. Our purpose is to evaluate our hypothesis that the treatment with lyophilized powder of enzymolyzed honeybee larvae as a complementary medicine may provide a therapeutic effect on tinnitus-related symptoms. DESIGN: Sixty tinnitus sufferers participated in a randomized double-blind placebo-controlled trial using the lyophilized powder of enzymolyzed honeybee larvae or a placebo. The Tinnitus Handicap Inventory, a visual analog scale to rate the severity of tinnitus, hearing levels, and hypothalamus-pituitary-adrenal axis-related hormones drawn early in the morning were measured upon entry into the study and after 12 wk of follow-up. RESULTS: The lyophilized powder of enzymolyzed honeybee larvae was not superior to placebo with regard to the total score on the Tinnitus Handicap Inventory and the visual analog scale. However, subjects in the honeybee larvae group showed significant improvements in some items about depression associated with tinnitus, whereas subjects in the placebo group showed no improvement in any items. The honeybee larvae group showed significant improvements in the hearing levels at 2 and 4 kHz in the audiogram of the better ear. The intervention of the lyophilized powder of enzymolyzed honeybee larvae was associated with lower serum cortisol levels, serum prolactin levels, and cortisol/dehydroepiandrosterone sulfate ratios. The ratios in the placebo group significantly were increased. CONCLUSIONS: Our results suggest that the lyophilized powder of enzymolyzed honeybee larvae represents an effective complementary medicine to alleviate depression associated with tinnitus by regulating the activity of the hypothalamus-pituitary-adrenal axis.


Assuntos
Apiterapia/métodos , Abelhas , Audição , Larva , Zumbido/terapia , Idoso , Animais , Ansiedade/terapia , Abelhas/crescimento & desenvolvimento , Corticosterona/metabolismo , Sulfato de Desidroepiandrosterona/metabolismo , Depressão/terapia , Enzimas , Feminino , Liofilização , Humanos , Sistema Hipotálamo-Hipofisário/fisiologia , Masculino , Pessoa de Meia-Idade , Sistema Hipófise-Suprarrenal/fisiologia , Pós , Zumbido/psicologia
17.
J Sex Med ; 8(11): 2960-82; quiz 2983, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22032408

RESUMO

INTRODUCTION: The circulation of large amounts of dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEA-S) suggests a physiological role in human physiology. In the central nervous system, DHEA is considered a neurosteroid with a wide range of functions. AIM: The goal of this review is to discuss metabolism, biochemical, and physiological mechanism of DHEA action and the potential role of DHEA in aging and in ameliorating a host of pathological conditions, associated with aging. METHODS: We examined preclinical and clinical data reported in various studies from the available literature concerning the effects of DHEA in normal and pathological conditions. MAIN OUTCOME MEASURES: Data reported in the literature were analyzed, reviewed, and discussed. RESULTS: DHEA mediates its action via multiple signaling pathways involving specific membrane receptors and via transformation into androgen and estrogen derivatives (e.g., androgens, estrogens, 7α and 7ß DHEA, and 7α and 7ß epiandrosterone derivatives) acting through their specific receptors. These pathways include: nitric oxide synthase activation, modulation of γ-amino butyric acid receptors, N-methyl D-aspartate, receptors sigma receptors (Sigma-1), differential expression of inflammatory factors, adhesion molecules and reactive oxygen species, among others. Clinical and epidemiological studies suggested that low DHEA levels might be associated with ischemic heart disease, endothelial dysfunction, atherosclerosis, bone loss, inflammatory diseases, and sexual dysfunction. Most importantly, no significant adverse or negative side effects of DHEA were reported in clinical studies of men and women. CONCLUSIONS: DHEA modulates endothelial function, reduces inflammation, improves insulin sensitivity, blood flow, cellular immunity, body composition, bone metabolism, sexual function, and physical strength in frailty and provides neuroprotection, improves cognitive function, and memory enhancement. DHEA possesses pleiotropic effects and reduced levels of DHEA and DHEA-S may be associated with a host of pathologies; however, the clinical efficacy of DHEA supplementation in ameliorating patho-physiological symptoms remains to be evaluated.


Assuntos
Desidroepiandrosterona/fisiologia , Envelhecimento/fisiologia , Animais , Composição Corporal/fisiologia , Osso e Ossos/metabolismo , Doenças Cardiovasculares/fisiopatologia , Desidroepiandrosterona/biossíntese , Desidroepiandrosterona/metabolismo , Sulfato de Desidroepiandrosterona/metabolismo , Depressão/fisiopatologia , Endotélio Vascular/fisiologia , Feminino , Humanos , Imunidade Celular/fisiologia , Inflamação/fisiopatologia , Masculino , Comportamento Sexual/fisiologia , Pele/metabolismo
18.
Curr Opin Endocrinol Diabetes Obes ; 18(3): 171-6, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21478748

RESUMO

PURPOSE OF REVIEW: Levels of dehydroepiandrosterone (DHEA) are known to decline with age. In an era of increasing use of supplements to better life, the benefits of DHEA in the aging female population are controversial. The goal of this article is to critically review published studies to determine if there is a role for DHEA supplementation in postmenopausal women. RECENT FINDINGS: Daily administration of oral DHEA achieves serum concentrations similar to those of women in their 20s. Several observational studies have shown that lower DHEA levels are associated with increased cardiovascular risk in women; however, interventional trials show no improvement in atherosclerosis or cardiovascular risk factors, and a lowering of HDL cholesterol levels. DHEA supplementation modestly increases bone mineral density in conjunction with adjuvant therapies and improves cognition in those with mild-to-moderate cognitive impairment, but does not affect cognition in unimpaired women. Use of intravaginal DHEA, but not oral DHEA, alleviates vaginal atrophy and improves sexual function in postmenopausal women. SUMMARY: On the basis of current evidence, there is no role for oral DHEA supplementation in healthy, postmenopausal women. Where benefits have been shown, long-term studies are needed to confirm these benefits and verify the safety profile of DHEA.


Assuntos
Sulfato de Desidroepiandrosterona/metabolismo , Pós-Menopausa/metabolismo , Atrofia/prevenção & controle , Densidade Óssea , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Transtornos Cognitivos/prevenção & controle , Sulfato de Desidroepiandrosterona/administração & dosagem , Suplementos Nutricionais , Feminino , Humanos , Risco , Vagina/patologia
19.
Neuropharmacology ; 61(7): 1172-81, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21251916

RESUMO

Studies have shown that anabolic androgenic steroids (AASs) can induce profound changes to mental health. Commonly reported psychiatric side effects among AAS users include aggression, anxiety, depression, drug abuse and cognitive disabilities. In experimental animals, many of these effects have been associated with alterations in a number of neurotransmitter systems. We have observed that chronic administration of the AAS nandrolone (nandrolone decanoate) can affect excitatory amino acids as well as monoaminergic and peptidergic pathways in a way that is compatible with nandrolone-induced behavioural changes. The aim of the present work was to further explore the mechanisms underlying nandrolone-induced effects, with a particular focus on components known to be involved in aggression and cognitive function. Male rats were given daily injections of nandrolone decanoate for 14 days and the effects on neurosteroid interactions with sites on the N-methyl-D-aspartyl (NMDA) and sigma receptors were examined. These receptors were chosen because of their involvement in aggressive and cognitive behaviors and the hypothesis that nandrolone might affect the brain via interaction with neurosteroids. Radiolabelled [³H]ifenprodil was used in the binding studies because of its significant affinity for the NMDA and sigma receptors. The results indicated that [³H]ifenprodil binds to both sigma-1 and sigma-2 sites and can be displaced to a certain extent from both sites by the neurosteroids pregnenolone sulphate (PS), pregnanolone sulphate (3α5ßS) and dehydroepiandrosterone sulphate (DHEAS). The remainder of the [³H]ifenprodil was displaced from the sigma-1 site by the sigma-1 receptor-selective ligand (+)-SKF 10,047. Chronic nandrolone treatment changed the sigma-1 receptor target for the neurosteroids but not for ifenprodil. The sigma-2 receptor site was unaltered by treatment with nandrolone decanoate. The results also indicated that the neurosteroid-induced allosteric modulation of the NMDA receptor subunit NR2B was not affected by nandrolone treatment. We conclude that chronic treatment with nandrolone changes the affinity of the neurosteroids PS, 3α5ßS and DHEAS at the sigma-1 site but not at the sites on the sigma-2 receptor or the NMDA receptor subunit NR2B.


Assuntos
Anabolizantes/farmacologia , Androgênios/farmacologia , Lobo Frontal/efeitos dos fármacos , Nandrolona/farmacologia , Neurotransmissores/metabolismo , Receptores sigma/metabolismo , Regulação Alostérica/efeitos dos fármacos , Anabolizantes/administração & dosagem , Anabolizantes/efeitos adversos , Androgênios/administração & dosagem , Androgênios/efeitos adversos , Animais , Sulfato de Desidroepiandrosterona/metabolismo , Lobo Frontal/metabolismo , Cinética , Masculino , Nandrolona/administração & dosagem , Nandrolona/efeitos adversos , Nandrolona/análogos & derivados , Decanoato de Nandrolona , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Pregnanolona/análogos & derivados , Pregnanolona/metabolismo , Pregnenolona/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/metabolismo , Receptor Sigma-1
20.
Neurosci Lett ; 483(2): 123-6, 2010 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-20691758

RESUMO

The study has shown that in aged (22-24 months) rat brains an elevation of homocysteine level (42%) and a decrease in dehydroepiandrosterone sulphate (DHEA-S) content (32%) occur compared to those in the brains of young rats (4-6 months). Such changes in the brain levels of homocysteine and DHEA-S in aged rats are prevented, when the diet daily of the rats is supplemented with a combination of antioxidants (N-acetyl cysteine 50 mg, alpha-lipoic acid 3 mg and alpha-tocopherol 1.5 mg - each per 100 g of body weight) starting from 18 months until these are sacrificed between 22 and 24 months. The brain content of reduced glutathione is also decreased in aged rats as compared to that in young ones and the phenomenon can again be prevented completely by the same regimen of antioxidant supplementation. The changes in the levels of homocysteine and DHEA-S in aged rat brain have been related to associated glutathione depletion and oxidative stress and the implications of the results highlighted in the pathogenesis of Alzheimer's disease.


Assuntos
Envelhecimento/metabolismo , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Antioxidantes/metabolismo , Encéfalo/metabolismo , Sulfato de Desidroepiandrosterona/metabolismo , Homocisteína/metabolismo , Envelhecimento/efeitos dos fármacos , Doença de Alzheimer/diagnóstico , Animais , Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Modelos Animais de Doenças , Ratos , Ratos Wistar
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