Effect of DHEA on Recovery of Muscle Atrophy Induced by Parkinson's Disease

PURPOSE: The purpose of this study was to determine the effect of dehydroepiandrosterone (DHEA) on recovery of muscle atrophy induced by Parkinson's disease. METHODS: The rat model was established by direct injection of 6-hydroxydopamine (6-OHDA, 20 microg) into the left striatum using stereotaxic surgery. Rats were divided into two groups; the Parkinson's disease group with vehicle treatment (Vehicle; n=12) or DHEA treatment group (DHEA; n=22). DHEA or vehicle was administrated intraperitoneally daily at a dose of 0.34 mmol/kg for 21 days. At 22-days after DHEA treatment, soleus, plantaris, and striatum were dissected. RESULTS: The DHEA group showed significant increase (p<.01) in the number of tyrosine hydroxylase (TH) positive neurons in the lesioned side substantia nigra compared to the vehicle group. Weights and Type I fiber cross-sectional areas of the contralateral soleus of the DHEA group were significantly greater than those of the vehicle group (p=.02, p=.00). Moreover, extracellular signal-regulated kinase (ERK) phosphorylation significantly decreased in the lesioned striatum, but was recovered with DHEA and also in the contralateral soleus muscle, Akt and ERK phosphorylation recovered significantly and the expression level of myosin heavy chain also recovered by DHEA treatment. CONCLUSION: Our results suggest that DHEA treatment recovers Parkinson's disease induced contralateral soleus muscle atrophy through Akt and ERK phosphorylation.

Effects of dehydroepiandrosterone on Th2 cytokine production in peripheral blood mononuclear cells from asthmatics

BACKGROUND/AIMS: The androgen dehydroepiandrosterone (DHEA) attenuates allergic inflammatory airway reactions by down-regulating the Th2 response in mice. The purpose of this study was to investigate whether DHEA suppresses Th2 cytokine production in cultured peripheral blood mononuclear cells (PBMCs) from asthmatic patients. METHODS: Sixty-one consecutive suspected asthmatic or non-asthmatic men underwent tests for asthma. PBMCs from each subject were cultured with and without DHEA (0.01~10 micrometer) for 48 h. The concentrations of interferon (IFN)-gamma, interleukin (IL)-5, and IL-10 in the culture supernatant were measured via an enzyme-linked immunosorbent assay. RESULTS: In PBMCs from subjects exhibiting methacholine airway hyperresponsiveness (AHR), DHEA significantly suppressed IL-10, IL-5, and IFN-gamma production in a dose-dependent manner (all p<0.001) and tended to increase the IFN-gamma/IL-5 ratio (p=0.087). DHEA (10 micrometer) suppressed cytokine production to a greater degree in subjects with AHR compared with those without AHR (IL-5: 24.0+/-7.8% vs. 40.9+/-3.6%, p<0.01; IFN-gamma: 29.7+/-7.0% vs. 54.5+/-5.1%, p<0.01). Cytokine suppression was significantly related to AHR, serum total IgE levels, and skin reactivity to house dust mites. CONCLUSIONS: DHEA suppressed both Th1 and Th2 responses, with a Th1 bias, and the degree of suppression was associated with the severity of AHR or atopy. Therefore, DHEA may be a useful therapy for asthma.

Anti-lipidperoxidative role of exogenous dehydroepiendrosterone (DHEA) administration in normal ageing rat brain.

Effects of exogenous dehydroepiendrosterone (DHEA) administration on the levels of lipid proxidation products, malondialdyde (MDA)-a thiobarbuteric acid reactive substance (TBARS) and 4-hydroxynonenal (4-HNE) in different brain regions viz. cerebral cortex, hippocampus cerebellum, and brain stem of 12 and 22 months old rats were studied. DHEA treatment significantly depressed TBARS and 4-HNE in all the brain regions studied, in both the age group rats. Interestingly, the magnitude of decrease was higher in the 22 months old rats than that in 12 months old rats. The results suggest that older the animal, better will be the response of exogenous DHEA administration against age-related peroxidative products.

Effect of DHEA on Hindlimb Muscles in a Focal Cerebral Ischemia Model Rat / 간호학회지

PURPOSE: The purpose of this study was to determine the effect of DHEA on hindlimb muscles(soleus, plantaris and gastrocnemius) in a focal brain ischemia model rat. METHOD: Twenty-seven male Sprague-Dawley rats were randomly divided into three groups: CINS(cerebral ischemia + normal saline), CIDH(cerebral ischemia + DHEA), or SHNS(sham + normal saline). Both the CINS and CIDH groups underwent a transient right middle cerebral artery occlusion operation. In the SHNS group, a sham operation was done. 0.34mmol/kg DHEA was administered daily by an intraperitoneal injection for 7days. RESULT: The muscle weight, muscle fiber cross-sectional area of the Type I muscle fiber of soleus and Type II muscle fiber of plantaris and gastrocnemius, myofibrillar protein content of gastrocnemius, and muscle strength in the CINS group decreased compared with the SHNS group. The muscle weight, muscle fiber cross-sectional area of the Type II muscle fiber of plantaris and gastrocnemius, myofibrillar protein content of soleus, and muscle strength in the CIDH group increased compared with the CINS group. CONCLUSION: It was identified that muscle atrophy could be induced during 7 days after a cerebral infarction, and DHEA administration during the early stages of a cerebral infarction might attenuate muscle atrophy.

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

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

Cystogenesis of antral follicles induced by dehydroepiandrosterone (DHEA) stimulates mast cell proliferation and maturation in the house rat (Rattus rattus) ovary.

Mast cell dynamics has been studied in relation to cystogenesis of ovarian follicles in the house rat. Immature rats were injected (s.c.) daily with DHEA (6.0 mg/100 g body weight) and were sacrificed on the day 8, 16 and 24 of the start of treatment. Ovarian sections of the treated rats had majority of the antral follicles undergoing atresia or in early stages of cystogenesis. Completely developed cysts were evident from the ovarian surface after 24 days of daily treatment. Treatment for 8 days resulted in significant increase in the number of alcian blue-positive ovarian mast cells. Ovaries after 16 days of DHEA treatment showed no marked change with regard to the number of total mast cells per unit area and staining characteristics. However, a significant rise in ovarian mast cell counts was recorded after 24 days of treatment and most of the cells contained safranin-positive red granules. This increase was attributed due to the increase in their number in medulla and stroma around the cystic follicles.

Efectos de la dehidroepiandrosterona sobre las células sanguineas de la rata / Effects of dehydroepiandrosterone on blood cells of the rat

Se estudió el efecto de la dehidroepiandrosterona (DHEA) sobre los niveles de hemoglobina, hematocrito y leucocitos en ratas machos y hembras; en ratas castradas y en hembras preñadas. La administración subcutánea de 80 mg/kg/d de DHEA durante 5 días consecutivos no modificó en ninguno de los grupos los valores de hemoglobina y hematocrito. En las ratas no cadastradas el número de leucocitos circulantes disminuyó en un 40 por ciento con una franca reducción en el número de linfocitos. La castración aumentó en un 14 por ciento el número de leucocitos y la adiministración de la DHEA los redujo al valor inicial. La administración del benzoato de estradiol, a ratas castradas, produjo un efecto similar al inducido por la DHEA. Se concluye que, en ratas, la administración de la DHEA no afecta el número de eritrocitos pero sí modifica el número de leucocitos presentes en sangre periférica.

Involvement of dietary glucose in adrenal steroidal regulation of spermatogenic and steroidogenic activities in prepubertal rat testis.

Effects of dietary and supplemented dextrose energy on the role of corticosterone (Comp. B) or dehydroepiandrosterone (DHA) in spermatogenic and steroidogenic activity in the bilaterally adrenalectomised prepubertal rat testis were studied. Adrenalectomy reduced the body and testis weight, numbers of the stage VII cell types [spermatogonia A (A), preleptotene (PL) and pachytene (P) spermatocytes and step 7 spermatid (7)], testicular delta 5-3 beta-hydroxysteroid dehydrogenase (delta 5-3 beta-OH-SDH) activity and serum testosterone. Adrenalectomy also caused reduction of energy intake due to loss of appetite which was stimulated by hormone replacement therapy. Treatment of adrenalectomised rats with DNA or corticosterone enhanced the spermatocyte population and the enzyme activity, especially after 30 days of age. Dextrose supplementation with hormone treatment however, did not produce significant additive effect on stage VII cell counts, but delta 5-3 beta-OH-SDH activity showed additive effect in this age group. Results suggest that adrenal steroids regulate testicular steroidogenesis and spermatogenesis during the prepubertal ages by modifying the supply of dietary glucose.

Potente efeito estrogênico dos esteróides das supra-renais (C19) no crescimento e níveis dos receptores da progesterona em tumores mamários induzidos pelo dimetilbenzeno-antraceno (DMBA) nas ratas / Potent estrogenic effect of adrenal steroids (C19) on growth and levels of progesterone receptors in mammary tumors induced by dimethyl-benzanthracene (DMBA) in rats

Nós estudamos o efeito do tratamento com os esteróides da supra-renais o androstenodiol (delta5-diol) e a dihidroepiandrosterona (DHEA) no crescimento e níveis dos receptores da progesterona em tumores mamários induzidos pelo DMBA nas ratas. Enquanto poucos tumores apareceram nas ratas ooforectomizadas (OOF), (média de 0,60 ñ 0,19/rata) após 24 dias, nas ratas OOF tratadas com delta 5 -diol ou DHEA (2mg, duas vezes por dia), as médias foram 2,54 ñ 0,50 (p < 0,01) e 1,42 ñ 0,26 (p < 0,01) respectivamente. O aparecimento de tumores novos foi muito reduzido nas ratas OOF (0,07 ñ 0,07/rata) durante os 24 dias de observaçäo, com uma média de 0,47 ñ 0,19/rata (p < 0,05) nas ratas intactas. Nas ratas OOF tratadas com delta5-diol ou DHEA o número de tumores novos foram 0,77 ñ 0,26 (p < 0,05) e 0,42 ñ 0,15 (p < 0,05) por animal, respectivamente. Um efeito ainda mais marcante foi observado na área média total dos tumores, os quais decresceram de 4,70 ñ 0,95 cm* nas ratas intactas para 0,75 ñ 0,27 cm* (p < 0,01) após ooforectomia. Valores de 9,79 ñ 2,25 (p < 0,01) e 3,93 ñ 0,86 cm* (p < 0,01) foram encontrados nas ratas OOF tratadas com delta5-diol e DHEA, respectivamente. As ratas OOF tratadas com delta5-diol e DHEA, mostraram um aumento altamente significante (p < 0,01) nos níveis dos receptores da progesterona nos tumores mamários e nos úteros. O peso uterino estava também aumentado (p < 0,01), pelo tratamento com estes dois esteróides das supra-renais. Estes resultados demonstram, pela primeira vez, que os dois esteróides C19 das supra-renais delta5-diol e DHEA, possuem um efeito estimulatório análogo aos dos estrógenos no crescimento e níveis dos receptores da progesterona em tumores mamários induzidos pelo DMBA nas ratas, desta forma comprovando sugestöes do papel importante destes esteróides das supra-renais no câncer de mama e outras patologias estrógeno-sensíveis na espécie humana