92 research outputs found
Hormonal effects of prohormones : novel approaches towards effect based screening in veterinary growth promoter control
No full textWithin the European Union the use of growth promoting agents in cattle fattening is prohibited according to Council Directive 96/22/EC. Interestingly, there is not a black list of substances, but 96/22/EC states that all substances having thyrostatic, estrogenic, androgenic or gestagenic activity are prohibited. Besides abuse of the “classical” synthetic steroids there is a tendency towards misuse of natural steroids and prohormones. Prohormones are compounds that exhibit limited or no hormonal activity but are direct precursors of bioactive hormones and are intended to be converted to full active hormones via enzymatic processes in the body. However, knowledge about metabolism, the mode of action and excretion profiles in cattle is often unclear, and methods to detect abuse of prohormones in livestock production are lacking. Therefore, the aim of this thesis was to get insight into the hormonal action of prohormones and to develop novel in vitro and in vivo screening methods allowing effective surveillance on the illegal use of prohormones in livestock production. Hereby the emphasis was on developing effect based approaches to better meet Council Directive 96/22/EC. The bioactivity of a wide variety of supplements which contained prohormones were tested using a yeast androgen bioassay. For supplements containing solely prohormones the value of this bioactivity based screening appeared to be limited as they require metabolism to become active. Therefore, screening methods for animal feed, supplements and preparations were set-up by using the same yeast androgen bioassay in combination with bovine liver models as well as enzymatic and chemical deconjugation procedures to mimic in vivo metabolic bioactivation. The use of either bovine liver S9, liver slices, pure enzymes or alkaline hydrolysis showed that prohormones could be activated, resulting in a significant increase in bioactivity as determined by the androgen yeast bioassay. For the detection of prohormone abuse at the farm and/or slaughterhouse the usefulness of ‘omics’ based profiling techniques was investigated. Within this scope a comprehensive metabolomics based screening strategy for steroid urine profiling was developed. Comparison of urinary profiles revealed large differences between the profiles of controls and dehydroepiandrosterone (DHEA) as well as pregnenolone treated animals. Moreover this steroid urine profiling approach allowed identification of biomarkers for treatment by specific prohormones. This resulted in respectively 7 and 12 specific mass peak loadings which could potentially be used as biomarkers for pregnenolone and DHEA treatment. In addition, the feasibility of a liver gene expression profiling approach was investigated to monitor the effects of DHEA treatment at the transciptome level. It was shown that identification and application of genomic biomarkers for screening of DHEA abuse in cattle is substantially hampered by biological variation. On the other hand, it was demonstrated that comparison of pre-defined gene sets versus the whole genome expression profile of an animal allows to distinguish DHEA treatment effects from variations in gene expression due to inherent biological variation. Altogether the results of this thesis increase the knowledge about the metabolism and bioactivation of prohormones in vitro as well as in vivo. Based on this knowledge, a panel of new effect based concepts and screening methods was developed that complement and improve the current testing programs. These new concepts will facilitate better implementation of the European ban on growth promoters in livestock production as described in Council Directive 96/22/EC. <br/
[[alternative]]In vitro Study on the Regulation og Human Immunoglobulin Production by Dehydroepiandrosterone(DHEA)
No full text[[abstract]]Dehydroepiandrosterone ( DHEA ) is a predominant androgen secreted by the adrenal cortex. Physiologically, DHEA appears as an intermediate of the androgen biosynthesis pathway. However, DHEA has been shown to play a multifunctional role in human and animal body. In addition, DHEA is a potential immunomodulator. DHEA regulates a variety of humoral and cellular immune response. Our previous report suggested that DHEA enhanced immunoglobulin secretion by murine B lymphocytes under in vitro condition. The same study also observed an antagonist effect of DHEA on the dexamethasone ( a glucocorticoid derivative )-mediated immunosuppression. The present study further extended the DHEA study from murine system to human immune cells. Data suggested that DHEA and DHEAS had no significant effect on the growth and viability of non-adherent peripheral blood mononuclear cells ( PMNC ). However, both drugs significantly augmented IgA and IgM secretion. Dexamethasone also enhanced IgA and IgM secretion by PMNC. Under our in vitro experimental condition, costimulating the cells with DHEA/DHEAS and dexmethasone shown a synergistic dffect on IgA and IgM secretion. To further investigate whether DHEA/DHEAS enhanced immunoglobulin secretion by direct stimulating the B lymphocytes, the growth and function of Dakiki ( an IgA secreting cells ) and SKW6.4 ( an IgM secreting cells ) in the presence of DHEA/DHEAS were studied. DHEA and DHEAS had no significant effect on the growth and viability of both Dakiki and SKW6.4. DHEA/DHEAS enhanced IgA and IgM secretion by Dakiki adb SKW6.4 cells, respectively dexamethasone suppressed the IgA secretion by IgA secretion by Dakiki. However, the dexamethasone- mediated suppressive effect could be overcome by both DHEA and DHEAS. In contrast, dexamethsaone enhanced IgM secretion by SKW6.4. Cosimulating the SKW6.4 with DHEA/DHEAS and dexamethasone has synergistic effect on IgM secretion. The IgM gene expression was studied by RT-PCR analysis. Result shown that the mRNA level of IgM in SKW6.4 cells were elevated after the cells were treated with DHEA, DHEAS or dexamethasone, suggesting that IgM production was stimulated at the transcription level.
High-fat diets exaggerate endocrine and metabolic phenotypes in a rat model of DHEA-induced PCOS
No full textPolycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder with unclear etiology and unsatisfactory management. Effects of diets on the phenotype of PCOS were not fully understood. In the present study, we applied 45 and 60% high-fat diets (HFDs) on a rat model of PCOS induced by postnatal DHEA injection. We found that both DHEA and DHEA + HFDs rats exhibited reproductive abnormalities, including hyperandrogenism, irregular cycles and polycystic ovaries. The addition of HFDs, especially 60% HFDs, exaggerated morphological changes of ovaries and a number of metabolic changes, including increased body weight and body fat content, impaired glucose tolerance and increased serum insulin levels. Results from qPCR showed that DHEA-induced increased expression of hypothalamic androgen receptor and LH receptor were reversed by the addition of 60% HFDs. In contrast, the ovarian expression of LH receptor and insulin receptor mRNA was upregulated only with the addition of 60% HFDs. These findings indicated that DHEA and DHEA + HFDs might influence PCOS phenotypes through distinct mechanisms: DHEA affects the normal function of hypothalamus-pituitary-ovarian axis through LH, whereas the addition of HFDs exaggerated endocrine and metabolic dysfunction through ovarian responses to insulin-related mechanisms. We concluded that the addition of HFDs yielded distinct phenotypes of DHEA-induced PCOS and could be used for studies on both reproductive and metabolic features of the syndrome.National Natural Science Foundation of China [81170538, 81471427]; National Key Technology R&D Program in the Twelve Five-Year Plan [2012BAI32B01]; China Postdoctoral Foundation [2015M570905]SCI(E)[email protected]
Identifikasi dan Observasi Histologi Letak Fungi Endofit yang Diisolasi dari Tanaman Jeruk Purut (Citrus hystix DC.)
No full textAbstrakFungi endofit merupakan kelompok fungi yang hidup di dalam jaringan tumbuhan tanpa menyebabkan kerusakan struktur jaringan tumbuhan inangnya. Sumber isolat fungi endofit dapat berasal dari tanaman berkhasiat obat, salah satunya yaitu tanaman jeruk purut (Citrus hystrix DC.). Tanaman ini mengandung beberapa senyawa aktif yaitu alkaloid, polifenol, minyak atsiri, tanin, flavonoid, dan saponin yang bersifat antimikroba. Penelitian ini bertujuan untuk 1) Mengidentifikasi fungi endofit yang diisolasi dari daun dan ranting tanaman jeruk purut secara in vitro, dan 2) Menentukan letak fungi endofit dalam jaringan daun dan ranting tanaman jeruk purut. Penelitian ini merupakan penelitian deskriptif eksploratif. Isolasi dilakukan secara aseptik dengan cara meletakkan potongan daun dan ranting jeruk purut di permukaan medium lempeng PDA, kemudian diinkubasikan dengan suhu 25-270C selama 3-7x24 jam. Setiap macam fungi endofit yang berhasil diisolasi kemudian dideskripsikan melalui pengamatan makroskopis dan mikroskopis dan dirujukkan pada buku kunci identifikasi fungi untuk menentukan nama spesies fungi endofit. Observasi letak fungi endofit dalam jaringan daun dan ranting jeruk purut dilakukan melalui pembuatan preparat irisan paradermal, longitudinal, dan transversal yang kemudian diamati dibawah mikroskop cahaya. Hasil penelitian menunjukkan bahwa, 1) spesies fungi endofit yang berhasil diisolasi dan diidentifikasi dari daun jeruk purut yaitu Colletotrichum alienum, Mycelia sterilia, C. queensiandicum, C. camalliae, dan C. siamense. Pada ranting jeruk purut ditemukan C. queensiandicum, C. gleosporioides, dan C.psidii; 2) hifa fungi endofit pada jaringan daun jeruk purut ditemukan di permukaan luar dinding sel: epidermis atas, palisade, dan sponsa, sedangkan dalam jaringan ranting jeruk purut ditemukan pada permukaan luar dinding sel: epidermis dan parenkima korteks. Kata Kunci: fungi endofit, daun jeruk purut, ranting jeruk purut AbstractEndophytic fungi are a group of fungi that live in plant tissue without causing damage to the host plant tissue. Structure the source of endophytic fungi isolates can be taken from medicinal plants, i.e: kaffir lime (Citrus hystrix DC.). This plant contains several active compounds, which is alkaloids, polyphenols, essential oils, tannins, flavonoids, and saponins that have antimicrobial effect. This study aims to 1) Identify endophytic fungi isolated from kaffir lime plants leaves and twigs in vitro, and 2) determine the location of endophytic fungi from kaffir lime plants leaves and twigs tissue. This research is a descriptive explorative research. The object in this study is endophytic fungi that live in the kaffir lime plants leaves and twigs. The kaffir lime leaves and twigs were cutted and inoculated acceptically on Potato Dextrose Agar (PDA) medium, than incubated at 25-270C for 7x24 hours. Each endophytic fungus isolates described by morphologic and microscopic observations. The observations result are referred to the fungi identification book to determine the endophytic fungi species. The location of the endophytic fungi were observed by paradermal, longitudinal, and transverse slide and observe microscopically. The research result shows that; 1) there are seven species endophytic fungi that were successfully isolated and identified from kaffir lime leaves; Colletotrichum alienum, Mycelia sterilia, C. queensiandicum, C. camalliae, and C. siamense. The endophytic fungi isolated from kaffir lime twig are C. queensiandicum, C. gleosporioides, and C.psidii; 2) the endophytic fungi hyphae isolated from kaffir lime leaves are found in the epidermal cell wall, palisade cell wall, sponge cell wall and on the kaffir lime twig are found in the epidermal cell wall and cortex paranchyma cell wall. Keywords: endophytic fungi, kaffir lime leaves, kaffir lime twi
The effect of dehydroepiandrosterone combined with a low-fat diet in spontaneously obese dogs: a clinical trial
No full textDehydroepiandrosterone (DHEA) has been shown to have antiobesity activity in rodents and spontaneously obese dogs. This study evaluated the effect of DHEA or placebo combined with a low-fat/high-fiber diet in spontaneously obese dogs in a clinical trial. Spontaneously obese, euthyroid dogs, referred to the University of Wisconsin School of Veterinary Medicine for treatment of their obesity, were evaluated for percent overweight, rate of weight loss, serum cholesterol, plasma lipoprotein and serum biochemistry profiles, complete blood count, and endocrine profiles (T4, T3, cortisol, insulin, and DHEA-sulfate). DHEA-treated dogs had a significantly increased rate of actual and percent excess weight loss compared with placebo-treated dogs. Serum cholesterol decreased in both treatment groups; however, DHEA-treated dogs had a significantly greater reduction than placebo-treated dogs. DHEA-treated dogs had a significant 32% reduction in total plasma cholesterol, which was due to a 27% reduction in the lipoprotein fraction containing the high-density lipoprotein (HDL) and a 50% reduction in the lipoprotein fraction containing the low-density lipoprotein (LDL). Placebo-treated dogs did not have a significant reduction in total plasma cholesterol or in the fraction containing LDL; however, they did have a significant 11% reduction in the fraction containing HDL. Significant decreases in serum T4 and T3 observed in dogs receiving DHEA were not noted in dogs receiving placebo. DHEA in combination with caloric restriction results in a faster rate of weight loss than does caloric restriction alone. In addition, DHEA has hypocholesterolemic activity, particularly affecting the lipoprotein fraction containing the LDL cholesterol.ID: 1593; LR: 20061115; JID: 9305691; 0 (Cholesterol, HDL); 0 (Cholesterol, LDL); 0 (Placebos); 50-23-7 (Hydrocortisone); 53-43-0 (Dehydroepiandrosterone); 57-88-5 (Cholesterol); 6893-02-3 (Triiodothyronine); 7488-70-2 (Thyroxine); ppublishSource type: Electronic(1
[[alternative]]Study on the role of dehydroepiandrosterone in regulation of specific antibody response
No full text[[abstract]]Abstract
Dehydroepiandrosterone (DHEA) is one of the major androgens secreted by adrenal cortex and play a multifunctional role in regulating physiological system in mammals. DHEA is predominantly converted to DHEA-sulfate (DHEAS) in serum . Recent reports demonstrated that DHEA is a potent immunomodulator. In addition, recent data showed that DHEA might act as an effective vaccine adjuvant in aged human and mice. However, the immunostimulatory effect on the children and young animal upon immunization remain to be studied. Furthermore, the profile of cytokine associated with DHEA-mediated regulatory effect remained to be defined. The major purpose of this study is to investigate the possible immunostimulatory effect of DHEA on the young mice immunized with Escherichia coli (E.coli O78:H11), combined diphtheria, tetanus, acellular pertussis vaccine (DPT vaccine) or pertussis toxin (PT), and to investigate the profile of cytokine associated with DHEA administration. Results indicated that DHEA has an augmented effect on the young mice immunized with Escherichia coli (E.coli O78:H11) or pertussis toxin (PT). However, DHEA did not show adjuvant effect on DPT vaccine immunized mice. In the subsequent study, the mice were infected with E. coli or challenged with PT, followed by subcutaneous injection with DHEA. Result indicated that DHEA synergistically enhanced E. coli or PT induced IFN-g, IL-2 and IL-4, IL-10 cytokine productions. Therefore, the immunoregulatory effect of DHEA might closely relate with its ability to modulate cytokine production. This study not only confirmed the ability of DHEA to regulate specific antibody response, but also demonstrated the role of DHEA in regulation of cytokine production.
[[alternative]]Regulatory role of dehydroepiandrosterone on B cell immuno-
No full text[[abstract]]Dehydroepiandrosterone (DHEA) 是腎上腺皮質分泌雄性激素時之前
驅物。前人報告提出DHEA對Ｔ淋巴球、巨噬細胞之功能及白血球新生具有
顯著之調節功能。本實驗證明 DHEA 對Ｂ淋巴球分泌Ig之功能也有影響。
DHEA與脂多醣體同時刺激Ｂ淋巴球時，對IgA有促進的作用，IgG及IgM 的
分泌則無影響。DHEA在Ｂ淋巴球受脂多醣體活化24小時後加入，則對 IgA
及IgG 的分泌有促進作用，對IgM分泌卻有明顯的抑制情形。DHEA 對Ｂ淋
巴球功能的調節不受 Anti IL-2 之影響，但受 Anti TGF-.beta.影響。
顯示 TGF-.beta. 參與DHEA對Ｂ淋巴球功能之調節作用。當DHEA與脂多醣
體同時加入時，Anti TGF-.beta. 抑制了DHEA所誘導之IgA分泌 ，但反而
促進IgG與IgM之分泌，顯示DHEA在Ｂ淋巴球活化初期可促進 IgG與 IgM分
泌，但是受TGF-.beta.所抑制，不過DHEA間接利用TGF-.beta.促進了IgA
之分泌。當 DHEA 在Ｂ淋巴球以脂多醣體活化24小時之後加入，則 Anti
TGF-.beta.抑制了DHEA對三種 Ig分泌的調節效應，顯示DHEA對活化後之
Ｂ細胞只藉TGF-.beta.之協助，才能調節Ｂ細胞之功能。 DHEAS為DHEA在
血清中存在的主要形式，但是DHEAS 對Ｂ淋巴球的功能無顯著影響。Dexa
-methasone為 glucocorticoid 之衍生物，對Ｂ淋巴球的增生、存活率及
IgA 分泌皆有顯著抑制作用，而DHEA可以拮抗Dexamethasone 的抑制作用
。DHEA直接或間接對免疫球蛋白分泌之調節作用，為內分泌與免疫系統之
關係提供了重要佐證，而 DHEA 與 glucocorticoid 之間之拮抗作用也顯
示體內，這兩種類固醇荷爾蒙平衡的重要性。
Dehydroepiandrostone(DHEA), a precusor androgen biosynthesis
in adrenal cortex, has been show to regulate the functions of T
lymphocytes and macrophages,and to suppress the lymphopoisis and
myelopoisis. Theresults of this study indicate that DHEA also
has ability to modulateB cell immunoglobulin secretion. DHEA did
enchance IgA secretion buthad no effect on IgG and IgM secretion
when B cells were stimulated by DHEA and lipopolysaccharide(LPS)
at the same time. However, if DHEA was added 24 hours after LPS
induced B cell activation, both the IgA and IgG secretion were
enhanced but IgM secration was suppressed by DHEA.The modulatory
function of DHEA on B cells was not affected by anti-inteleukin2
(IL-2) antibodies but it was significant affected by anti trans-
forming growth factor .beta.( TGF-.beta. ), suggesting that TGF-
.beta.was involved in DHEA-mediated immunoregulation. Anti TGF-
.beta. inhibited DHEA induced IgA secretion but significantly
enhanced IgG and IgMsecretion when B cells were stimulated by
DHEA and LPS at the same time. It implied that DHEA could enhance
IgG and IgM secreation during theearly stage of B cell activation
.However, both IgG and IgM secretionwere suppressed by TGF-.beta.
. On the contrary, TGF-.beta. together with DHEA induced IgA
secretion. Anti-TGF-.beta. completely abrogated the immunoregu-
latory function of DHEA when B cells were stimulated by DHEA 24
hoursafter LPS-induced activiation, suggesting that the presence
of TGF-.beta. is essential for DHEA to regulate the function of
activated B cells, DHEAS , the specific form of DHEA in serum,
showed no effect on immunogloublin secretion. Dexamethasone, a
derivative of glucocorticoid, suppressed B cell growth, reduced
B cell viability and IgA secretion. Results in this study showed
that DHEA significantly antagonized immunosuppresive effect of
dexamethasone. The observation that DHEA directlyor indirectly
regulated immunoglobulin secretion provided an additional evi-
dence to demonstrate the close relationship between endocrine
andimmune system. Furthermere, the counter reaction between DHEA
and glucocorticoid suggested that it is essential to maintance
the properratio between these two important steroid hormone in
body fluid.
Dehydroepiandrostone(DHEA), a precusor androgen biosynthesis
Subcellular redistribution of NHERF1 in response to dehydroepiandrosterone (DHEA) administration in endometrial glands of Wistar rats
Full text linkTo understand the regulation of Na(+)/H(+) exchanger regulatory factor (NHERF1) in polycystic ovarian syndrome, we studied the expression of NHERF1 in uterus of Wistar rats injected with (6 mg/kg) of dehydroepiandrosterone (DHEA) for 7 and 20 days. Immunohistochemistry analysis of NHERF1 showed a substantial shift in the intracellular localization of NHERF1 in endometrial glands and areas of luminal epithelium as early as 7 days of DHEA administration. The NHERF1 accumulated in the "Golgi apparatus area" virtually in all the glands in the 7-day protocol, and in the majority of the glands of 20-day protocol. In contrast, NHERF1 is expressed in the apical membrane and slightly in the cytoplasm of the control epithelium. The subcellular redistribution of NHERF1 could affect the sorting of proteins to the apical membrane and the organization of the apical compartment. © 2013 The Author(s).Fil: Kreimann, Erica Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Unidad Presidencia; Argentina. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); ArgentinaFil: Cabrini, Rómulo L.. Comisión Nacional de Energía Atómica. Gerencia de Area de Aplicaciones de la Tecnología Nuclear. Gerencia de Radiobiología (Centro Atómico Constituyentes); Argentin
[[alternative]]An in vivo regulatory role of dehydroepiandrosterone in murine TNF-alfa and TGF-beta production
No full text[[abstract]]Dehydroepiandrosterone (DHEA) is a predominant androgen secreted by adrenal cortex. DHEA has been proposed to play an important role in regulating physiological and immunological system in mammals. Our previous report suggested that DHEA caused an enhancement in TNF-alfa and TGF-beta production by both P388D1 cells and peritoneal macrophage under in vitro condition. The specific aim of present study is to investigate whether DHEA have ability to regulate TNF-alfa and TGF-beta production under in vivo condition. Balb/c mice administrated DHEA subcutaneously were sacrificed at 72 hrs after the treatment, then the serum and peritoneal macrophages were collected. The peritoneal macrophages were cultured with LPS for a period of time and the supernatant was then collected. Both TNF-alfa and TGF-b concentration were quantified using ELISA kits. Results suggested that the TNF-alfa secretion by peritoneal macrophages from the mice injected with 50 ug per g body weight and 100 ug per g body weight of DHEA were significantly increased and reached peak 6 hr after incubation. However, the amount of TNF-alfa secretion by macrophages returned to control level when the dose higher than 100 ug per g body weight was given. Result from RT-PCR analysis confirmed the finding that expression of TNF-alfa mRNA was enhanced by in vivo administration of DHEA. By contrast, the serum level of TNF-alfa was not significantly affected by the drug treatment. The TGF-beta secretion by peritoneal macrophages under in vitro culture did not show a significant difference from mice receiving carrier (100 % ethanol). However, the serum level of TGF-beta of mice injected with 100 ug per g body weight of DHEA was significantly lower than the mice received carrier. Dexamethasone is a potent immunosuppressor. Mice injected 1ug per g body weight of dexamethasone showed a significant reduction in TNF-alfa secretion by peritoneal macrophages. However, injection of DHEA together with dexamethasone could overcome the immunosupressive effect of dexamethasone on TNF-alfa secretion. The serum level of TNF-alfa did not show a significant change in dexamethasone treated mice but it showed a significantly increase in the mice received both DHEA and dexamethasone. Mice received dexamethasone showed a significant increase in the serum level of TGF-beta. However, DHEA could not antagonize the augmented effect of dexamethasone on the serum level of TGF-beta. In conclusion, mice injected DHEA potentiated the TNF-alfa production by peritoneal macrophages but decreased the serum level of TGF-beta. Since the effect of DHEA on both TNF-alfa and TGF-beta production might be interfered by other factors under in vivo condition, the effect of DHEA on the serum level of TNF-alfa and the TGF-beta was not significant. In addition, DHEA might be an effective antagonist to overcome the suppressive effect of dexamethasone on TNF-alfa secretion in vivo.
[[alternative]]Role of interleukin-10 in dehydroepiandrosterone-mediated immunoglobulin production
No full text[[abstract]]英文摘要
DHEA is a predominant androgen secreted by the adrenal cortex zona reticularis. DHEA appears as an intermediate of the androgen biosynthesis pathway and play a multifunctional role in regulating physiological system in mammals. The accumulated documents have demonstrated that DHEA and DHEAS are the potential immunomodulator that regulate both humoral and cellular immune response. Previous reports showed that DHEA and DHEAS were able to enhance the immunoglobulin production by murine spleen B lymphocytes、human peripheral blood mononuclear cells (PMNC) and B-cell lymphoid cell lines (Dakiki and SKW6.4) under in vitro condition. The present study extended the previous finding to in vivo system. In this study, the male Balb/c mice were injected subcutaneously with various doses of DHEA or DHEAS based on the body weight. The mice were then sacrified at different time point after the drug treatment and both spleen lymphocytes and serum were collected. Results indicated that both the growth rate and viability of the spleen lymphocytes were reduced after 6 days of in vitro culture. However, the amounts of immunoglobulin (IgG、IgA and IgM) secreted by the cells and the serum level of immunoglobulin were increased. The optimal dose for enhancing immuno-globulin secretion was 250 mg per gram body weight and the period for the maximal effect was 48 hrs after the treatment. The previous reports suggested that cytokine including interleukin-10 (IL-10) were able to modulate the immuno-globulin production. In this study, the role of IL-10 in DHEA/DHEAS-mediated increase in immunoglobilin production was investigated. Results indicated that both DHEA and DHEAS were able to enhance the production of IL-10 by the conA-stimulated murine spleen cells. This regulatory activity of DHEA and DHEAS appeared on the messenger RNA level. To further confirm the role of IL-10, the mice were injected with both DHEA and an anti-mouse IL-10 mAb simultaneously. Result showed that the amount of IL-10 produced by the spleen cells was reduced and the serum level of IL-10 was decreased after the antibody treatment. In consistent with the IL-10 level, the amount of immunoglobulin secreted by spleen cells and the serum level of the immunoglobulin were significantly decreased. In conclusion, DHEA might enhance the immunoglobulin production by activing Th2 pathway and increasing IL-10 production.
- …
