36 research outputs found

    Prolonged adrenal stimulation does not affect plasma DHEA in the dairy cow

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    Introduction: In primates, adrenal DHEA secretion is episodic and displays a diurnal rhythm in parallel to that of cortisol, and it is responsive to ACTH stimulation. In the dairy cow, circulating DHEA originates primarily from the gonads, while the adrenal contribution has been poorly investigated. The aim of this work was to study DHEA release under prolonged adrenal stimulation in the dairy cow. Materials and Methods: Five healthy non-lactating, non-pregnant Friesian cows were used. The experiment included a control phase followed by a treatment phase with a 30-day resting period in between. During each phase, estrus was synchronized with two injections of cloprostenol (PG) administered 11 days apart. The second PG administration was referred as Day 0. From Day –2 to Day 3, animals received i.m. injections of either saline (control phase) or ACTH analogue (Synacthen depot, 0.7 mg/head/administration; treatment phase) every 12 hours. Plasma cortisol and DHEA concentrations were monitored every 8 hours on Days -3, -2, -1, 2, 3, 5 and 9. On Day 4, hormone release and response to naloxone were studied in plasma samples taken every 10 minutes for 8 hours. Naloxone was administered after 4 hours. Results: During the treatment phase, plasma cortisol was significantly higher (P<0.01) from Day –1 to Day 5, while plasma DHEA was not affected by treatment. Frequent sampling performed on Day 4 did not reveal any pattern of episodic DHEA release. Mean DHEA plasma levels were significantly higher during the treatment phase (P<0.01), but no response to naloxone administration was observed. Mean plasma cortisol significantly increased during the treatment phase (P<0.001), and was significantly reduced by naloxone administration (P<0.05). During the treatment phase, cortisol pulse amplitude was significantly greater before naloxone administration (P<0.05). Conclusions: These data suggest that adrenal over-stimulation has a negligible effect on circulating DHEA in the dairy cow

    Tumor necrosis factor inhibits conversion of dehydroepiandrosterone sulfate (DHEAS) to DHEA in rheumatoid arthritis synovial cells: A prerequisite for local androgen deficiency

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    Objective. Use of anti-tumor necrosis factor (anti-TNF) antibody therapy in rheumatoid arthritis (RA) has expanded our understanding of possible mechanisms by which this treatment reduces inflammation. Beyond its effects on local immune responses, anti-TNF treatment may also modulate the local hormone supply. Because androgens are thought to inhibit immune responses, their presence in inflamed tissue is an additional important antiinflammatory factor. Methods. We investigated conversion of the ubiquitous dehydroepiandrosterone sulfate (DHEAS), the biologically inactive precursor of DHEA, to the androgen DHEA in mixed synovial cells from patients with RA and patients with osteoarthritis (OA), making use of thin-layer chromatography and phosphorimaging. Using immunohistochemical analysis, we detected the key enzyme, steroid sulfatase. Results. DHEAS-to-DHEA conversion in synovial cells from patients with RA was significantly lower than that in synovial cells from patients with OA (mean +/- SEM 3.3 +/- 0.5% versus 6.0 +/- 0.9% of applied H-3-DHEAS per 106 synovial cells; P = 0.042). In RA, but not in OA, the level of converted 3 H-DHEA was inversely correlated with the density of synovial macrophages (for RA, R-rank = -0.725, P = 0.005; for OA, R-rank = 0.069, P not significant [NS]) and T cells (for RA, Rrank = - 0.621, P = 0.024; for OA, R-rank = 0.247, P NS). Double immunohistochemistry analysis revealed that steroid sulfatase was located mainly in synovial macrophages but was also observed in fibroblasts. Neutralization of TNF largely up-regulated the conversion of DHEAS to DHEA in RA, but not in OA. A similar neutralizing effect was observed with polyclonal human immunoglobulins; this effect is most probably mediated via TNF neutralization at low TNF concentrations. Conclusion. These data indicate that TNF inhibits the conversion of DHEAS to DHEA in RA synovial cells. Because androgens are antiinflammatory mediators, TNF-induced inhibition of the local androgen supply is a supplementary proinflammatory factor. Consequently, anti-TNF strategies may also exert their positive effects by increasing tissue androgens

    Effect of aging and reproductive condition on dehydroepiandrosterone plasma levels in the bitch

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    Although biomedical research has devoted much effort on the effect of aging and reproductive condition on plasma concentration of dehydroepiandrosterone (DHEA) in women (Longcope, 1986) these aspects have never been investigated in the bitch. In fact, studies on DHEA plasma levels in the dog have been focused mainly on male reproductive physiology and, as far as we know, only one strudy investigated DHEA plasma concentration in the bitch. This sole paper (Queiroga et al., 2005), focused on the role of different steroids in the pathogenesis of canine mammary tumours, reports mean DHEA levels in plasma samples obtained from both anaestrous and ovariectomized bitches aged between 6 and 14 years. The aim of the present study is to verify whether reproductive condition and aging could affect DHEA plasma concentrations in the bitch, making these parameters important when planning experimental studies on DHEA in this species

    Levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate in the cerebrospinal fluid of healthy dogs and dogs affected by neurological disorders.

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    Aged dogs develop neuropathology and pattern of cognitive decline that mirrors that seen in both successfully aging humans and patients with senile cognitive dysfunctions. Although biomedical research has devoted much effort on neurobiological effects of steroids and neurosteroids on aging nervous system this aspect has never been investigated in the dog. The present research aims to explore the possible role of two neurosteroids, namely dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS), in the central nervous system of the dog. Animals included in the study underwent complete neurological evaluation in the clinical facilities of the Faculty of Veterinary Medicine of Padua (Italy). Thirty nine cerebrospinal fluid (CSF) samples were obtained from healthy dogs (N = 7) and dogs affected by various neurological disorders (compressive myelopathy, N = 8; degenerative myelopathy, N=5; other neurological disorders, N=19). The CSF samples were divided in 3 groups based on the age of the dogs and tested for DHEA and DHEAS concentrations by RIA. Mean CSF levels of DHEA and DHEAS were 74,8 pg/ml and 15,8 pg/ml respectively, and no significant differences were found between animal affected or not affected by neurological diseases. On the contrary, analysis of variance showed significant effect of age (P < 0,05) on steroid level ratio (DHEAS/DHEA) which resulted higher in young adult animals (Duncan test). In addition, DHEAS/DHEA ratio was significantly lower (Mann-Whitney test; P < 0,01) in dogs affected by degenerative myelopathy, while DHEAS concentration was higher in dogs affected by compressive myelopathy (Mann-Whitney test; P < 0,01). These data provide the first evidence of the presence of DHEA and its sulfate in the CSF of the dog. Moreover, the variation of their CFS levels related to aging and to neurological condition suggests a role of DHEA and DHEAS in the physiopathology of the canine central nervous system. The results deepen neuroendocrine aspects related to canine aging and provide compelling support for the aged dog as a model of human cognitive aging and disorders

    Plasma steroid variations in bull calves repeatedly treated with testosterone, nortestosterone and oestradiol administered alone or in combination

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    The aim of this work was to investigate the secretion of dehydroepiandrosterone (DHEA), testosterone (T), dihydrotestosterone (DHT) and oestradiol (E) as biological markers in response to illegal administration of testosterone, 19-nortestosterone (N) and oestradiol, either alone or in combination. Twenty male Friesian calves (age 13-14 months) were allotted to a control group (n = 5), and five experimental groups (n = 3) each. Each experimental animal was repeatedly injected with one of the following hormonal treatments: E, T, N, T+E and N+E. Circulating DHEA, T, DHT and E were determined by radioimmunoassay. The administration of T alone did not induce any variation in plasma DHEA, T, DHT and E, which were similar to those in the control group. In contrast, DHEA, T and DHT were on average significantly lower in the T+E and N-treated groups (p < 0.01), whereas the administration of N+E resulted in the reduction of plasma T and DHT without any modification of plasma DHEA. The administration of E alone or in combination increased circulating levels of E but did not affect androgen plasma profiles. The results indicate that plasma levels of T do not permit detection of illegal treatments because plasma androgens always remained within the physiological range. Illegal E treatment could be detected in blood samples when they were collected at least every 20 days

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

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    Plasma concentrations of dehydroepiandrosterone (DHEA), 5-androstene-3beta,17beta-diol (AED), and 17beta-estradiol (E2) in dairy cows and heifers and AED binding to uterine cytosolic estrogen receptor (ER) were studied. Plasma samples were collected from the subcutaneous abdominal (SA) and jugular (J) veins of heifers and cows in the non-pregnant state and at 15-45, 90-120, 180-210, and 250-280 days of pregnancy (N = 5-12). Plasma DHEA, AED, and E2 were determined by RIA. DHEA and AED significantly increased (P < 0.001) in heifers and cows throughout pregnancy. The stage of pregnancy significantly (P < 0.001) affected the three steroids in heifers and cows. Plasma DHEA increased throughout pregnancy in both heifers and cows, and in heifers it was significantly greater in SA than in J veins at 90-120 days (P < 0.01). Plasma AED was greater in heifers than in cows in J veins at 90-120 days (P < 0.01) and 180-210 days (P < 0.05), and in SA veins, at 15-45 days (P < 0.01) and 90-120 days (P < 0.05). In heifers, circulating AED showed concentration values significantly greater than those in non-pregnant animals from 90 to 120 days (P < 0.05) and was significantly greater in SA than in J veins at 90-120 days (P < 0.05). In cows, plasma AED was significantly greater than in non-pregnant animals at 250-280 days (P < 0.01). In heifers, plasma E2 was significantly greater in the SA than in the J veins from 180-210 to 250-280 days (P < 0.01). In cows, differences between E2 plasma concentrations in J and SA veins were observed only at 250-280 days of pregnancy. At 250-280 days, in both animal types plasma E2 was significantly greater than in non-pregnant animals (P < 0.001). We suggest that AED originates primarily from the feto-placental unit, while mammary E2 synthesis near term can affect plasma concentrations. Binding data showed that AED is a weak competitor for cytosolic ER (IC50 range: 1.44 x 10(-5) to 3.71 x 10(-5) M). These results suggest that a direct estrogenic activity for AED is unlikely in dairy cattle, and the physiological role of AED needs to be elucidated

    Gender effect on the relationship between stress hormones and panic-agoraphobic spectrum dimensions in healthy subjects.

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    INTRODUCTION: Alterations of the hypothalamic-pituitary-adrenal (HPA) axis and of its peripheral indices have been reported in both normal and pathological anxiety with controversial findings. The aim of the present study was to investigate the possible correlations between serum cortisol and dehydroepiandrosterone-sulfate (DHEA-S) levels and DHEA-S/cortisol ratio, and panic-agoraphobic spectrum dimensions in a sample of healthy subjects. METHODS: Forty-two healthy subjects of both sexes, with no current or lifetime psychiatric disorders, were assessed by means of the Structured Clinical Interview for DSM-IV (SCID-I/P) and the so-called Panic Agoraphobic Spectrum-Self Report lifetime version (PAS-SR). RESULTS: Significant, negative correlations were found between cortisol levels and the total score of the separation sensitivity, panic-like symptoms, and medication/substance sensitivity PAS-SR domains. The PAS-SR total and the panic-like symptoms domain scores were positively related to the DHEAS/cortisol ratio. When the sample was divided in women and men, these correlations were present in women only. DISCUSSION: These findings, while indicating the presence of significant relationships between panic-agoraphobic traits and some indices of HPA axis functioning in healthy women, would suggest this as one of the factors explaining the greater vulnerability of women to cross the line between normal and pathological anxiety. CONCLUSIONS: Further studies are needed to explore gender differences in the relationships between HPA axis alterations and the panic-agoraphobic spectrum dimensions

    Oral dehydroepiandrosterone supplementation modulates spontaneous and growth hormone-releasing hormone-induced growth hormone and insulin-like growth factor-1 secretion in early and late postmenopausal women

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    Objective: To evaluate the effects of dehydroepiandrosterone (DHEA) supplementation on the growth hormone-releasing hormone-growth hormone (GHRH-GH) axis in lean and obese postmenopausal women. Design: Prospective study. Setting: Postmenopausal women in a clinical research environment. Patient(s): Thirty-one postmenopausal women were divided in two groups by age (50 to 55 and 60 to 65 years). Within each group, lean and obese patients were considered. Intervention(s): All patients underwent hormonal evaluations before and at the third and sixth month of therapy (50 mg of DHEA orally each day) and a GHRH test (1 μg/kg) before and at the sixth month of treatment. Ultrasound and bone mass density (BMD) examinations were performed before and after the sixth month of therapy. Main Outcome Measure(s): Plasma dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), E1, E2, androstenedione (A), testosterone (T), osteocalcin, GH, insulin-like growth factor 1 (IGF-1) concentrations. Result(s): The levels of all of the steroids that derived from DHEA metabolism (E1, E2, A, T, DHEAS) and osteocalcin were increased in plasma under DHEA supplementation. The supplementation protocol also increased the levels of GH and IGF-1. However, GHRH-induced GH and IGF-1 responses were not modified by DHEA supplementation. Conclusion(s): Administration of DHEA significantly affects several endocrine parameters in early and late postmenopausal women independently from body mass index. Our data support the hypothesis that DHEA treatment acts similarly to estrogen-progestin replacement therapy on the GHRH-GH-IGF-1 axis. This suggests that DHEA is more than a more than a simple "diet supplement" or "antiaging product"; rather it should be considered an effective hormonal replacement treatment. © 2001 by American Society for Reproductive Medicine

    Androgen conversion in osteoarthritis and rheumatoid arthritis synoviocytes – androstenedione and testosterone inhibit estrogen formation and favor production of more potent 5α-reduced androgens

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    In synovial cells of patients with osteoarthritis (OA) and rheumatoid arthritis (RA), conversion products of major anti-inflammatory androgens are as yet unknown but may be proinflammatory. Therefore, therapy with androgens in RA could be a problem. This study was carried out in order to compare conversion products of androgens in RA and OA synoviocytes. In 26 OA and 24 RA patients, androgen conversion in synovial cells was investigated using radiolabeled substrates and analysis by thin-layer chromatography and HPLC. Aromatase expression was studied by immunohistochemistry. Dehydroepiandrosterone (DHEA) was converted into androstenediol, androstenedione (ASD), 16 alpha OH- DHEA, 7 alpha OH-DHEA, testosterone, estrone (E1), estradiol (E2), estriol (E3), and 16aOH- testosterone (similar in OA and RA). Surprisingly, levels of E2, E3, and 16 alpha-hydroxylated steroids were as high as levels of testosterone. In RA and OA, 5 alpha-dihydrotestosterone increased conversion of DHEA into testosterone but not into estrogens. The second androgen, ASD, was converted into 5 alpha-dihydro-ASD, testosterone, and negligible amounts of E1, E2, E3, or 16 alpha OH-testosterone. 5 alpha-dihydro-ASD levels were higher in RA than OA. The third androgen, testosterone, was converted into ASD, 5 alpha-dihydro-ASD, 5 alpha-dihydrotestosterone, and negligible quantities of E1 and E2. 5 alpha-dihydrotestosterone was higher in RA than OA. ASD and testosterone nearly completely blocked aromatization of androgens. In addition, density of aromatase- positive cells and concentration of released E2, E3, and free testosterone from superfused synovial tissue was similar in RA and OA but estrogens were markedly higher than free testosterone. In conclusion, ASD and testosterone might be favorable anti-inflammatory compounds because they decrease aromatization and increase anti- inflammatory 5 alpha-reduced androgens. In contrast, DHEA did not block aromatization but yielded high levels of estrogens and proproliferative 16 alpha-hydroxylated steroids. Androgens were differentially converted to pro- and anti-inflammatory steroid hormones via diverse pathways

    ANALISIS PEMBENTUKAN KARAKTER MANDIRI BERBANTUAN GERAKAN LAGU ANAK PADA SISWA KELAS I SDN 38 PALEMBANG

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    Abstrak Pembentukan karakter adalah suatu pendekatan yang mendukung perkembangan sosial, emosional, membentuk dan mengembangkan pembentukan karakter serta moralitas individu. Tujuan penelitian ini adalah untuk mengetahui pembentukan karakter mandiri berbantuan gerakan lagu anak pada siswa kelas IA dan untuk mengetahui hambatan apa saja yang dihadapi dalam pembentukan karakter mandiri berbantuan gerakan lagu anak pada siswa kelas I SDN 38 palembang. Teknik pengumpulan data pada penelitian ini menggunakan teknik observasi, wawancara dan dokumentasi. Setelah menerapkan pembentukan karakter mandiri berbantuan gerakan lagu anak, karakter mandiri pada peserta didik meningkat menjadi 95%, peserta didik hampir sudah memahami pentingnya mempunyai karakter mandiri sejak ini dan peserta didik memiliki perubahan yaitu sudah menerapkan karakter mandiri tersebut pada saat di lingkungan sekolah. Dengan proses pembentukan karakter mandiri berbantuan gerakan lagu anak, peserta didik lebih memahami dan bersemangat mengikuti proses pembelajaran di kelas. Sehingga terciptalah proses pembelajaran yang aktif dan inovatif.Kata Kunci : Pembentukan Karakter Mandiri, Gerakan Lagu AnakAbstrak Pembentukan karakter merupakan suatu pendekatan yang mendukung perkembangan sosial, emosional, membentuk dan mengembangkan pembentukan karakter dan moralitas individu. Tujuan penelitian bantuan ini adalah untuk mengetahui pembentukan karakter mandiri dengan gerak lagu anak pada siswa kelas IA dan untuk mengetahui kendala apa saja yang dihadapi dalam membentuk karakter mandiri dengan bantuan gerak lagu anak pada siswa kelas I SDN 38 palembang. Teknik pengumpulan data dalam penelitian ini menggunakan teknik observasi, wawancara dan dokumentasi. Setelah terbentuknya karakter mandiri dengan bantuan gerakan lagu anak, karakter mandiri siswa meningkat hingga 95%, siswa sudah hampir memahami pentingnya memiliki karakter mandiri sejak saat ini dan siswa sudah berubah yaitu sudah menerapkan hal tersebut. karakter mandiri selama berada di lingkungan sekolah. Dengan adanya proses pembentukan karakter mandiri dengan bantuan gerakan lagu anak, siswa lebih memahami dan antusias mengikuti proses pembelajaran di kelas. Sehingga terciptalah proses pembelajaran yang aktif dan inovatif.Kata Kunci: Pembentukan Karakter Mandiri, Gerakan Lagu Anak
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