Molecular basis for control of antibiotic production by a bacterial hormone.

Actinobacteria produce numerous antibiotics and other specialized metabolites that have important applications in medicine and agriculture1. Diffusible hormones frequently control the production of such metabolites by binding TetR family transcriptional repressors (TFTRs), but the molecular basis for this remains unclear2. The production of methylenomycin antibiotics in Streptomyces coelicolor A3(2) is initiated by the binding of 2-alkyl-4-hydroxymethylfuran-3-carboxylic acid (AHFCA) hormones to the TFTR MmfR3. Here we report the X-ray crystal structure of an MmfR-AHFCA complex, establishing the structural basis for hormone recognition. We also elucidate the mechanism for DNA release upon hormone binding through the single-particle cryo-electron microscopy structure of an MmfR-operator complex. DNA binding and release assays with MmfR mutants and synthetic AHFCA analogues define the role of individual amino acid residues and hormone functional groups in ligand recognition and DNA release. These findings will facilitate the exploitation of actinobacterial hormones and their associated TFTRs in synthetic biology and in the discovery of new antibiotics.

What is a hormone?

Starling's original definition of a hormone from 1905 was "a hormone is a substance produced by glands with internal secretion, which serve to carry signals through the blood to target organs". Today, this definition is understood to be lacking, but newer definitions also do not encompass the entire meaning of hormones as specific carriers of information. One main problem is that there is no delineation between hormones and other signaling molecules such as cytokines, growth factors or autacoid compounds. It seems that a precise definition is not even possible, since some cytokines and growth factors, such as the cytokines erythropoietin, lipocalin-2 and asprosin or fibroblast growth factor 23, act as hormones under certain conditions.

Interplay between hormones and exercise on hippocampal plasticity across the lifespan.

The hippocampus is a brain structure known to play a central role in cognitive function (namely learning and memory) as well as mood regulation and affective behaviors due in part to its ability to undergo structural and functional changes in response to intrinsic and extrinsic stimuli. While structural changes are achieved through modulation of hippocampal neurogenesis as well as alterations in dendritic morphology and spine remodeling, functional (i.e., synaptic) changes can be noted through the strengthening (i.e., long-term potentiation) or weakening (i.e., long-term depression) of the synapses. While age, hormone homeostasis, and levels of physical activity are some of the factors known to module these forms of hippocampal plasticity, the exact mechanisms through which these factors interact with each other at a given moment in time are not completely understood. It is well known that hormonal levels vary throughout the lifespan of an individual and it is also known that physical exercise can impact hormonal homeostasis. Thus, it is reasonable to speculate that hormone modulation might be one of the various mechanisms through which physical exercise differently impacts hippocampal plasticity throughout distinct periods of an individual's life. The present review summarizes the potential relationship between physical exercise and different types of hormones (namely sex, metabolic, and stress hormones) and how this relationship may mediate the effects of physical activity during three distinct life periods, adolescence, adulthood, and senescence. Overall, the vast majority of studies support a beneficial role of exercise in maintaining hippocampal hormonal levels and consequently, hippocampal plasticity, cognition, and mood regulation.

A Brief History of Modern Endocrinology and Definitions of a True Hormone.

BACKGROUND AND OBJECTIVE: An overview of the history of endocrinology indicates that definitions of some initially developed concepts, including the term 'hormone' have been changed over time. This review provides a historical overview of current definitions of 'hormone' and the criteria of a true hormone. In addition, a brief history of hormone-related concepts and their transformation over time are discussed. RESULTS: Classically, a hormone is a chemical substance secreted into the bloodstream and acts on distant tissues, usually in a regulatory fashion. Several newly discovered bioregulators and chemical signaling molecules are far from the classical definition of a true hormone and could not fulfill many relevant criteria. Major developments in the field of endocrinology accompanied by the complex terminology, currently used to describe hormonal actions of chemical messengers, underscore the need of the revision of such classical concepts. CONCLUSION: Complex terminology currently used to describe different hormonal actions of chemical messengers, suggests that it is time to conceptualize the term hormone and revise its classical definition.

Colecalciferol regula os parâmetros hematológicos e a produção de citocinas pró-inflamatórias renais em camundongos diabéticos e nas células RAW 264. 7 / Colecalciferol regulates haematological parameters and the production of renal proinflammatory cytokines in diabetic mice and RAW 264. 7 cells

Os efeitos causados pelo tratamento em conjunto da insulina e do colecalciferol em indivíduos diabéticos não estão completamente elucidados. O presente trabalho avaliou o efeito de ambos os hormônios nos rins, no fígado, no coração e nos parâmetros hematológicos de camundongos machos (C57BL/6) sadios e diabéticos, bem como a ação do colecalciferol (in vitro) na resposta imunológica desenvolvida pelas células RAW 264.7 e pelos macrófagos peritoneais (MP) após estímulo com lipopolissacarídeo (LPS). Após dez dias da administração da aloxana (60 mg/kg), animais diabéticos exibiram redução do ganho de peso corporal e hiperglicemia quando comparados aos animais que receberam salina. No sétimo dia do período experimental, foi verificado que animais diabéticos que não receberam nenhum hormônio, em relação aos não diabéticos, exibiram redução do peso corporal, dos níveis de hemoglobina (Hb), hematócrito, hematimetria, insulina, TNF-α e IL-6 (coração) e aumento da glicemia, da relação peso corpóreo/peso rim esquerdo, das concentrações séricas de ureia, creatinina, Fosfatase Alcalina (FAL), Lactato desidrogenase (LDH) e lactato, fator de necrose tumoral (TNF)-α, interleucina (IL)-6 e IL-10 (no rim); o tratamento com insulina (1 UI/300 mg/dL glicemia), em relação aos animais diabéticos não tratados, promoveu aumento do peso corporal, das concentrações séricas de insulina e redução da glicemia, das concentrações séricas de ureia e da razão TNF-α/IL-10 (coração); o tratamento com colecalciferol (800 UI/dia), em relação aos animais diabéticos não tratados, promoveu aumento das concentrações séricas de 25-hidroxicolecalciferol [25(OH)D], Hb, hematócrito, hematimetria, IL-10 (coração) e reduziu IL-6, IL-10, TNF-α e EPO (rim); os animais diabéticos tratados com insulina, em relação aos animais diabéticos suplementados com colecalciferol apresentaram aumento do peso corpóreo, de ureia sérica, IL-6 e TNF-α (coração) e redução da glicemia, das concentrações séricas de lactato, de IL-6, TNF-α, IL-10 e EPO (rim); os animais -que receberam ambos os hormônios, em relação aos animais tratados com insulina, apresentaram aumento sérico de insulina e lactato; os animais diabéticos que receberam ambos os hormônios, em relação aos animais diabéticos tratados com colecalciferol, exibiram aumento sérico de 25(OH)D, de insulina, além da redução das concentrações de IL-10, da razão de TNF-α/IL-10 e TNF-α/IL-6 (coração); animais diabéticos que receberam ambos os hormônios, em relação aos diabéticos não suplementados com colecalciferol, exibiram: aumento de insulina sérica e redução das concentrações séricas de ureia e das razões renal e hepática de TNF-α/IL-6; células RAW 264.7 estimuladas pelo LPS e tratadas com 100 nM colecalciferol exibiram maior expressão da CYP27B1 e redução na liberação de mediadores inflamatórios quando comparadas ao grupo estimulado pelo LPS. Entretanto, não foi observado o mesmo efeito nos MP. Em conjunto, os resultados sugerem que: 1) em animais diabéticos, o colecalciferol pode modular parâmetros hematológicos e que a insulina pode melhorar a função renal, bem como a recuperação do peso corporal; 2) o colecalciferol pode ser metabolizado pelas células RAW 264.7 e modular a resposta imunológica desencadeada pelo LPS

The effects caused by the treatment of insulin and cholecalciferol in diabetic subjects are not completely elucidated. The present study evaluated the effect of both hormones on the kidneys, liver, heart and hematological parameters of healthy and diabetic male mice (C57BL/6), as well as the action of cholecalciferol (in vitro) on the immune response developed by the cells RAW 264.7 and peritoneal macrophages (MP) after stimulation with lipopolysaccharide (LPS). After ten days of alloxan administration (60 mg/kg), diabetic animals exhibited a reduction in body weight gain and hyperglycemia when compared to animals that received saline. On the seventh day of the experimental period, it was verified that diabetic animals that did not receive any hormones, in relation to non-diabetics, showed reduction of body weight, hemoglobin (Hb), hematocrit, hematimetry, insulin, TNF-α and IL- 6 (heart) and increased glycemia, body weight / left kidney weight, serum urea, creatinine, Phosphatase Alkaline, lactate dehydrogenase (LDH) and lactate levels, tumor necrosis factor (TNF) interleukin (IL) -6 and IL-10 (in the kidney); diabetic mice treated with insulin (1 IU / 300 mg/dL glycemia) in relation to untreated diabetic animals promoted increased body weight, serum insulin levels and blood glucose lowering, serum urea levels and TNF-α ratio / IL-10 (heart); diabetic animals treated with cholecalciferol (800 IU/day), in relation to untreated diabetic animals, exhibited increased serum levels of 25-hydroxycholecalciferol [25 (OH) D], Hb, hematocrit, hematimetry, IL-10 (heart) and reduced IL-6, IL-10, TNF-α and EPO (kidney);insulin-treated diabetic animals compared to diabetic animals supplemented with cholecalciferol exhibited an increase of body weight, serum urea, IL-6 and TNF-α (heart) and a reduction of glycaemia, serum lactate levels, IL-6, TNF- α, IL-10 and EPO (kidney); animals that received both hormones, compared to animals treated with insulin exhibited an increase of insulin and lactate serum levels; diabetic animals that received both hormones, compared to diabetic animals treated with cholecalciferol, exhibited an increase of 25(OH)D and insulin serum levels, and a reduction of IL-10, TNF-α/IL-10 and TNF-α/IL-6 ratios (heart); diabetic animals that received both hormones, compared to diabetic animals not supplemented with cholecalciferol, exhibited an increase of insulin and reduced urea serum levels and reduced renal and hepatic TNF-α/IL-6 ratios; LPS-stimulated RAW 264.7 cells and treated with 100 nM cholecalciferol exhibited greater CYP27B1 expression and reduced release of inflammatory mediators when compared to the LPS-stimulated group. However, the same effect was not observed in PM. Taken together, the results suggest that: 1) in diabetic animals, cholecalciferol may modulate hematological parameters and that insulin may improve renal function as well as recovery of body weight; 2) cholecalciferol can be metabolized by RAW 264.7 cells and modulate the immune response triggered by LPS

[Changes in endocrine profile of workers in pulp and paper plant.]

Examination covered 245 individuals and included characteristics of endocrine state of pulp and paper plant workers over 2011-2012, in comparison with data from 1990, as well as comparison with reference groups of male workers with no contact with chemical'industry in Arkhangelsk. Findings are both in main and reference groups general decrease in levels of cortisol, thyroxin;progesterone, testosterone, insulin, somatotropin and increased serum level of estradiol. With that, inside both groups, reliable tendencies to increased levels of cortisol, thyroxin, insulin, SSH and lower concentration of progesterone in the pulp and paper plant workers vs. the reference group members. Positive tendency was absence of abnormal concentrations of insulin, SSH and lower frequency of high cortisol levels in the pulp and paper plant workers nowadays.

Trinucleotide repeat expansions in human breast cancer-susceptibility genes: relevant targets for aspirin chemoprevention?

Purpose. Defining novel molecular mechanisms pertinent to aspirin chemoprevention of breast cancer (BC) and to explain controversial epidemiological results in this regard. Methods. Literature search in relevant databases with the following key words; aspirin, nucleotide repeat expansions, breast cancer. Human genome contains nucleotide repeat expansions and exon-1 of the androgen receptor gene AR contains a CAG string with an average of 20 repeats. Longer AR CAG repeats associate with lower AR protein functioning leading relatively higher estrogen receptor signals and higher risk of hormone receptor-positive BC. Nucleotide repeat expansions also exist in E2F4 and POLG genes in BC. In cell culture models, aspirin reduces CAG.CTG expansions in kidney cells and restores myogenic differentiation in cells obtained from tissues with myotonic dystrophy, a disorder caused by large CTG expansions. Conclusions. We hypothesize that aspirin reduction of trinucleotide repeat expansions in breast cancer-susceptibility genes may be one of the relevant mechanisms of its chemopreventive effects (AU)

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Principles of endocrinology.

The endocrine system plays a major role in human survival. Endocrine glands secrete chemical messengers or hormones that affect every tissue of the body, including the periodontium, during the life of the individual. As the endocrine system influences a broad assortment of biological activities necessary for life, a general understanding of the principal components and functions of this system is essential. A fundamental assessment of hormone structure, mechanism of action and hormone transport, as well as influence on homeostasis is reviewed. A concise evaluation of the functions of the central endocrine glands, the functions of the major peripheral endocrine glands (other than gonadal tissues) and the known relationships of these hormones to the periodontium is examined.

Comparison of the hormonal responses to exhaustive incremental exercise in adolescent and young adult males.

OBJECTIVE: Evaluate hormonal responses to incremental-stage exercise (EX) test to exhaustion in adolescents. SUBJECTS AND METHODS: Adolescents were tested at 16 years of age in Tanner Stage 4 (TS4) and at 17 years of age in Tanner Stage 5 (TS5) (n = 6). Adults were tested at 21 ± 1 y. (X ± SD) (n = 4) and served as controls. Blood samples were taken at rest, at the end of each EX stage. RESULTS: Main effects for EX in cortisol (p < 0.01, increasing with each EX stage) and for subject group for testosterone (T) occurred (p < 0.01; TS4 < TS5, adults). Interaction effect of group by EX stage occurred for GH (p < 0.05). GH increased in response to EX in all groups, however, the magnitude of increase was significantly less for TS5 and adults than TS4. CONCLUSIONS: Differences in T and GH responses for TS4 than those for TS5 and adults reflect the differing maturation levels of the endocrine system between Tanner Stages. TS5 adolescents are more similar to young adults in hormonal responses to EX than are TS4 adolescents.

Comparison of the hormonal responses to exhaustive incremental exercise in adolescent and young adult males / Comparação das respostas hormonais ao exercício incremental até exaustão em adolescentes e adultos jovens do sexo masculino

OBJECTIVE: Evaluate hormonal responses to incremental-stage exercise (EX) test to exhaustion in adolescents. SUBJECTS AND METHODS: Adolescents were tested at 16 years of age in Tanner Stage 4 (TS4) and at 17 years of age in Tanner Stage 5 (TS5) (n = 6). Adults were tested at 21 ± 1 y. (X ± SD) (n = 4) and served as controls. Blood samples were taken at rest, at the end of each EX stage. RESULTS: Main effects for EX in cortisol (p < 0.01, increasing with each EX stage) and for subject group for testosterone (T) occurred (p < 0.01; TS4 < TS5, adults). Interaction effect of group by EX stage occurred for GH (p < 0.05). GH increased in response to EX in all groups, however, the magnitude of increase was significantly less for TS5 and adults than TS4. CONCLUSIONS: Differences in T and GH responses for TS4 than those for TS5 and adults reflect the differing maturation levels of the endocrine system between Tanner Stages. TS5 adolescents are more similar to young adults in hormonal responses to EX than are TS4 adolescents.

OBJETIVO: Avaliar as respostas hormonais ao teste de exercício em estágios incrementais (EX) até exaustão. SUJEITOS E MÉTODOS: Foram examinados adolescentes com 16 anos de idade e índice Tanner 4 (TS4) e com 17 anos de idade e índice Tanner Stage 5 (TS5) (n = 6), e adultos com 21 ± 1 anos de idade. (X ± SD) (n = 4), estes últimos compondo o grupo controle. As amostras de sangue foram retiradas no repouso e ao final de cada estágio EX. RESULTADOS: Os principais efeitos observados no EX ocorreram no cortisol (p < 0,01, aumentou com a elevação do estágio EX) e no grupo de testosterona (p < 0,01; TS4 < TS5, adultos). Houve efeito de interação entre grupos e por estágio de EX no grupo de hormônio de crescimento (p < 0,05). O hormônio de crescimento aumentou em todos os grupos em resposta ao EX, no entanto, a magnitude dos aumentos observados foi significativamente menor em TS5 e nos adultos do que em TS4. CONCLUSÕES: As diferenças verificadas nas respostas dos grupos de testosterona e hormônio de crescimento em TS4 em relação ao TS5 e adultos refletem os diferentes níveis de maturação do sistema endócrino entre os estágios do índice de Tanner. Os adolescentes no TS5 se assimilam mais aos jovens adultos do que aos adolescentes TS4, quanto a suas respostas hormonais ao EX.

Occurrence of steroid hormones and antibiotics in shallow groundwater impacted by livestock waste control facilities.

Wastewater impoundments at concentrated animal feeding operations (CAFOs) represent a potential source of veterinary pharmaceuticals and steroid hormone contamination to shallow groundwater. This study investigates the occurrence of seventeen veterinary pharmaceuticals and thirteen steroid hormones and hormone metabolites in lagoons and adjacent groundwater at operating swine and beef cattle facilities. These sites were chosen because subsurface geology and previous monitoring of nitrate, ammonia and chloride levels in shallow ground water strongly indicated direct infiltration, and as such represent worst cases for ground water contamination by waste water. Pharmaceutical compounds detected in samples obtained from cattle facilities include sulfamerazine; sulfamethazine; erythromycin; monensin; tiamulin; and sulfathiazole. Lincomycin; ractopamine; sulfamethazine; sulfathiazole; erythromycin; tiamulin and sulfadimethoxine were detected in wastewater samples obtained from swine facilities. Steroid hormones were detected less frequently than veterinary pharmaceuticals in this study. Estrone, testosterone, 4-androstenedione, and androsterone were detected in wastewater impoundments at concentrations ranging from 30 to 3600ng/L, while only estrone and testosterone were detected in groundwater samples at concentrations up to 390ng/L. The co-occurrence of veterinary pharmaceutical and steroid hormone contamination in groundwater at these locations and the correlation between pharmaceutical occurrence in lagoon wastewater and hydraulically downgradient groundwater indicates that groundwater underlying some livestock wastewater impoundments is susceptible to contamination by veterinary pharmaceuticals and steroid hormones originating in wastewater lagoons.

Determinação da taxa metabólica basal em cutias, Dasyprocta azarae, por calorimetria indireta / Determination of the basal metabolic rate in agoutis, Dasyprocta azarae, by indirect calorimetry

A melhor ferramenta para comparação fisiológica entre organismos diferentes é a taxa metabólica basal, inter-relação fundamental que existe entre todos os seres vivos. Mensurações diretas das concentrações de oxigênio e dióxido de carbono, pela análise do ar inspirado e expirado, podem ser usadas para a mensuração de taxa metabólica. Este trabalho foi executado com o propósito de aferir as taxas metabólicas basal e específica, e reexaminar o escalonamento do metabolismo basal em cutias (Dasyprocta azarae). Foram utilizadas 34 cutias (D. azarae) adultas sadias, sendo 9 machos não castrados, 9 machos castrados e 16 fêmeas, pertencentes ao plantel do Criadouro Científico do Museu de História Natural Capão da Imbuia, Curitiba, PR. Os animais passaram por jejum prévio de 6 horas e foram acondicionados em caixas especiais, com temperatura ambiente controlada (22,0±1,0ºC), sendo então submetidos à aferição da taxa metabólica basal, por calorimetria indireta. Empregou-se o monitor metabólico Deltatrac®II, (Datex Ohmeda, Finlândia) usualmente indicado para a mensuração da produção de dióxido de carbono (VCO2) e do consumo de oxigênio (VO2) em seres humanos, por meio da mensuração das variações na concentração de VCO2 e de VO2, com uma precisão de 0,01 por cento. Após a aferição da taxa metabólica basal, foi calculada a taxa metabólica específica, e efetuada a análise dos dados por estatística indutiva. Os testes de hipóteses para comparação entre amostras indicaram que a taxa metabólica específica de machos não castrados é maior que a de fêmeas e machos castrados (5 por cento de significância), e que a taxa metabólica específica de fêmeas e machos castrados é equivalente (1 por cento de significância). Constatou-se ainda, com a análise da correlação de pontos experimentais, que outra variável que não o tamanho corporal afeta a taxa metabólica dos machos não castrados (1 por cento de significância), o que indica a necessidade de novos estudos sobre...

The best way to compare different organisms is the basal metabolic rate, a fundamental interrelation existent among all living beings. Direct measures of oxygen and carbon dioxide concentrations by evaluation of inspired and expired air can be used to measure metabolic rate. So, this research was done in order to measure basal and specific metabolic rates in agoutis (Dasyprocta azarae), and reexamine the scaling of basal metabolism in this species. There were used 34 adult healthy agoutis (9 non-castrated males, 9 castrated males, and 16 females), that belong to the wild animal scientific breeding facility of the Natural History Museum of the Curitiba city, State of Paraná, Brazil. After a six-hour fasting the animals were placed in special boxes under controlled temperature (22.0±1.0ºC), and submitted to measuring of the basal metabolic rate, by indirect calorimetry. It was used the Deltatrac®II metabolic monitor, usually indicated to measure carbon dioxide production (VCO2) and oxygen consumption (VO2) in human beings, by measuring variations in the concentration of VCO2 and of VO2, with a precision of 0.01 percent. The specific metabolic rate was calculated after determination of the basal metabolic rate and the obtained data were analyzed by inductive statistics. The hypotheses tests for comparison among samples indicated that the specific metabolic rate is higher in non-castrated males than in females and castrated males (significance of 5 percent), and that the specific metabolic rate of females and castrated males are equivalent (significance of 1 percent). In addition, analysis of the correlation of experimental points indicates that another variable beyond body size affects the metabolic rate of non-castrated males (significance of 1 percent), and therefore new studies on the metabolism of Dasyprocta azarae are required.

Major genomic events and their consequences for vertebrate evolution and endocrinology.

Comparative studies of proteins often face the problem of distinguishing a true orthologue (species homologue) from a paralogue (a gene duplicate). This identification task is particularly challenging for endocrine peptides and neuropeptides because they are short and usually have several invariant positions. For some peptide families, this has led to a terminology with peptide names relating to the first species where a specific peptide sequence was determined, such as chicken or salmon gonadotropin-releasing hormone, or names that highlight amino acid differences, e.g., Lys-vasopressin. With accumulating information from multiple species, such a terminology becomes almost impenetrable for nonexperts and difficult even for aficionados. The sequenced genomes offer a new way to distinguish orthologues and paralogues, namely by location of the genes relative to neighboring genes on the chromosomes. In addition, the genome databases can ideally provide a complete listing of the family members in each species. Many vertebrate gene families have expanded in the two basal tetraploidizations (2R) and the teleost fish third tetraploidization (3R), after which some vertebrate lineages have lost some of the duplicates. We review here some peptide families (neuropeptide Y, oxytocin-vasopressin, and somatostatin) where genomic information helps simplify nomenclature. This approach is useful also for other gene families, such as peptide receptors.

EndoNet: an information resource about regulatory networks of cell-to-cell communication.

EndoNet is an information resource about intercellular regulatory communication. It provides information about hormones, hormone receptors, the sources (i.e. cells, tissues and organs) where the hormones are synthesized and secreted, and where the respective receptors are expressed. The database focuses on the regulatory relations between them. An elementary communication is displayed as a causal link from a cell that secretes a particular hormone to those cells which express the corresponding hormone receptor and respond to the hormone. Whenever expression, synthesis and/or secretion of another hormone are part of this response, it renders the corresponding cell an internal node of the resulting network. This intercellular communication network coordinates the function of different organs. Therefore, the database covers the hierarchy of cellular organization of tissues and organs as it has been modeled in the Cytomer ontology, which has now been directly embedded into EndoNet. The user can query the database; the results can be used to visualize the intercellular information flow. A newly implemented hormone classification enables to browse the database and may be used as alternative entry point. EndoNet is accessible at: http://endonet.bioinf.med.uni-goettingen.de/.

Hormonal profile effects following dehydroepiandrosterone (DHEA) administration to schizophrenic patients.

Dehydroepiandrosterone (DHEA) is an important neurosteroid and has demonstrated efficacy in the improvement of mood and energy. The authors previously reported the efficacy of DHEA augmentation in the management of negative, depressive, and anxiety symptoms of schizophrenia. To characterize further the effects of DHEA administration and to describe any hormonal effects following DHEA augmentation of antipsychotic medication, several hormones were measured (TSH, prolactin, testosterone, insulin, and estradiol) in 27 chronic schizophrenic inpatients receiving DHEA or placebo augmentation for 6 weeks. No significant changes in hormonal blood measures were noted. At the study end point, an association was noted between DHEA-S and TSH levels (P < 0.05) as well as a change in DHEA-S and insulin levels (P < 0.001). A modest nonsignificant decrease in plasma testosterone was observed following DHEA treatment. In subjects receiving DHEA, change in testosterone levels was associated with improvement in anxiety (P < 0.05) and illness severity (P < 0.05). Findings in this preliminary study demonstrate minimal effects on hormonal profiles despite the theoretic possibility that DHEA may elevate various hormones (eg, testosterone) with potential long-term adverse effects. DHEA's clinical efficacy appears to be mediated by other mechanisms, including direct effects on membrane channel-coupled receptors.