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dehydroepiandrosterone indirectly inhibits human osteoclastic resorption via activating osteoblastic viability by the MAPK pathway

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Chinese Medical Journal 2012年第7期125卷 1230-1235页

作者： WANG Yu-dong TAO Min-fang CHENG Wei-wei LIU Xiao-hua WAN Xiao-ping KeMi Cui Department of Gynecology International Peace Maternal and Child Health HospitalShanghai Jiao Tong UniversityShanghai 200030China

Background dehydroepiandrosterone （DHEA） is widely known for its beneficial effect on postmenopausal osteoporosis, although the underlying mechanisms remain mainly unclear. In this study, we tried to determine the activation of mitogen-activated protein kinase signal pathways during DHEA treatment and the indirect role of osteoblasts （OBs） on osteoclasts under the DHEA treatment of postmenopausal osteoporosis. Methods Primary human OBs and osteoclast-like cells were cultured and, we pretreated OBs with or without U0126 （a highly selective inhibitor of both MEK1 and MEK2）. The OBs were treated with DHEA. We then tested the effects of DHEA on human osteoblastic viability, osteoprotegerin production and the expression of phosphor-ERK1/2 （extracellular signal-regulated kinase）. In the presence or absence of OBs, the function of osteoclastic resorption upon DHEA treatment was calculated. Results DHEA promoted the human osteoblastic proliferation and inhibited the osteoblastic apoptosis within the concentration range of 108-106 mol/L （P 〈0.05, P 〈0.01, respectively）. Within the effective concentration range, the expression of phosphor-ERK1/2 and osteoprotegerin was increased by DHEA and blocked by U0126. In the presence of OBs, DHEA could significantly decrease the number and the area of bone resorption lacuna （P 〈0.05 and P 〈0.01, respectively）. Without OBs, however, the effects of DHEA on the bone resorption lacuna were almost completely abolished. Conclusions DHEA could indirectly inhibit the human osteoclastic resorption through promoting the osteoblastic viability and osteoprotegerin production, which is mediated by mitogen-activated protein kinases signal pathway involving the phosphor-ERK1/2.

关键词： dehydroepiandrosterone osteoblasts osteoclast MAP kinase signaling pathways

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dehydroepiandrosterone Inhibited the Bone Resorption through the Upregulation of OPG/RANKL

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Cellular & Molecular Immunology 2006年第1期3卷 41-45页

作者： Yudong Wang Ling Wang Dajin Li Wenjun Wang Department of Obstetrics and Gynecology the Sixth People＇s Hospital Jiaotong University Shanghai 200233 China Laboratory for Reproductive Immunology Hospital and Institute of Obstetrics ＆ Gynecology Fudan University Shanghai Medical College Shanghai 200011 China

The plasma level of dehydroepiandrosterone （DHEA） is decreases gradually along with aging. The beneficial effects of DHEA as an anti-aging steroid, such as the stimulatory effect on immune system, anti-diabetes mellitus, antl-atherosclerosis, ***, anti-obesity and anti-osteoporosis have been demonstrated in experiment both in vitro and in vivo. It is important to investigate the effective mechanism of DHEA in therapeutics for postmenopausal osteoporosis. Having isolated and cultured osteoblasts （OBs） and osteoclasts （OCs）, we analysed the effect of DHEA on osteoblastic viability, regulation of DHEA on the expression of osteoprotegerin （OPG）/receptor activator of NF-κB Ugand （RANKL） mRNA in OBs, and then observed the action of DHEA on bone resorption of OCs in the presence or absence of OBs. The results showed that DHEA improved viability of OBs within the concentration range of 10^-8-10^-6 M, especially at the concentration of 10^-7 M. DHEA could apparently increase the ratio of OPG/RANKL mRNA in OBs. In the presence of OBs, DHEA could decrease the number and area of absorption lacuna of specula. We concluded, therefore, only in the presence of OBs, DHEA could inhibit the bone resorption of OCs, which may be mediated by OPG/RANKL of OBs.

关键词： dehydroepiandrosterone OPG/RANKL osteoblast

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dehydroepiandrosterone:a potential therapeutic agent in the treatment and rehabilitation of the traumatically injured patient

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Burns & Trauma 2019年第1期7卷 248-260页

作者： Conor Bentley Jon Hazeldine Carolyn Greig Janet Lord Mark Foster NIHR Surgical Reconstruction and Microbiology Research Centre University Hospital BirminghamBirmingham B152WBUK School of Sport Exercise and Rehabilitation SciencesUniversity of BirminghamBirminghamUK MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research Institute of Inflammation and AgeingBirmingham University Medical SchoolBirmingham B152TTUK NIHR Biomedical Research Centre University Hospital BirminghamBirminghamUK Royal Centre for Defence Medicine Birmingham Research ParkBirmingham B152SQUK.

Severe injuries are the major cause of death in those aged under 40,mainly due to road traffic ***,metabolic and immune pathways respond to limit the tissue damage sustained and initiate wound healing,repair and regeneration ***,depending on age and sex,the response to injury and patient prognosis differ *** are catabolic and immunosuppressive and are produced as part of the stress response to injury leading to an intra-adrenal shift in steroid biosynthesis at the expense of the anabolic and immune enhancing steroid hormone dehydroepiandrosterone(DHEA)and its sulphated metabolite dehydroepiandrosterone sulphate(DHEAS).The balance of these steroids after injury appears to influence outcomes in injured humans,with high cortisol:DHEAS ratio associated with increased morbidity and *** models of trauma,sepsis,wound healing,neuroprotection and burns have all shown a reduction in proinflammatory cytokines,improved survival and increased resistance to pathological challenges with DHEA *** supplementation studies,which have focused on post-menopausal females,older adults,or adrenal insufficiency have shown that restoring the cortisol:DHEAS ratio improves wound healing,mood,bone remodelling and psychological ***,there are no DHEA or DHEAS supplementation studies in trauma patients,but we review here the evidence for this potential therapeutic agent in the treatment and rehabilitation of the severely injured patient.

关键词： dehydroepiandrosterone dehydroepiandrosterone sulphate Traumatic injury Intensive care Immune Rehabilitation

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Effects of Ziyin Jianghuo Ningxin decoction plus dehydroepiandrosterone and femoston in treatment of patients with menopausal symptoms

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Journal of Traditional Chinese Medicine 2018年第5期38卷 787-796页

作者： Lin Jing Zhu Jun Tian Fubo Chen Lanting Zhang Yang Wang Yan Wang Mingyan Hans-Jurgen Gober Li Da-jin Wang Ling Laboratory for Reproductive Immunology Hospital &Institute of Obstetrics and GynecologyIBSShanghai Medical CollegeFudan UniversityShanghai 200032China Shanghai Key Laboratory of Female Reproductive Endocrine-related Diseases Shanghai 200011China The Academy of Integrative Medicine of Fudan Uni-versity Shanqhai 200032China Department of Obstetrics and Gynecology Wen-ling People's HospitalWenzhou Medical UniversityWenling 317500China Heilongjiang University of Chinese Medicine Heilongjiang 150040China Department of Pharmacy Kepler University ClinicNeuromed CampusLinzAustria

OBJECTIVE: To determine the therapeutic effect of Ziyin Jianghuo Ningxin Decoction(ZYJHNXD) plus dehydroepiandrosterone(DHEA) and menopausalhormone therapy(MHT) in patients suffering from menopausal symptoms identified as, in terms of Traditional Chinese Medicine, symptom pattern of Yin deficiency with hyperactive ***: Totally 180 postmenopausal women aged 40 to 60 years were assigned into four groups and accepted femoston, femoston with ZYJHNXD,femoston with DHEA, femoston with ZYJHNXD and DHEA therapies, respectively, for three *** questionnaire-based measure instruments included modified Kupperman index(MKI),Hamilton Rating Scale for Anxiety(HAMA), and Hamilton Rating Scale for Depression(HAMD). Follicle-stimulating hormone(FSH), luteinizing hormone(LH), estradiol(E2), 5-hydroxyindole-3-acetic acid(5-HIAA), norepinephrine(NE), dopamine(DA),bone mineral density(BMD), and sleep quality were evaluated before and three months after the ***: In all four groups, the scores of MKI, HAMA, HAMD and the levels of FSH, LH decreased significantly(P < 0.05) after the treatment, while the levels of E2, 5-HIAA, NE, and DA showed obvious elevation(P < 0.05). The group receiving ZYJHNXD and DHEA combined with femoston had superiority in the preservation of bone mineral density and improvement of total sleep time and nighttime sleep time over the other three ***: ZYJHNXD and DHEA combined with MHT therapy have a favorable outcome in managing menopausal symptoms, restoring hormone levels, preventing skeletal rarefaction or osteoporosis,and improving sleep quality for postmenopausal women.

关键词： Menopausal symptoms Menopausal hormone therapy Femoston,Ziyin Jianghuo Ningxin Decoction dehydroepiandrosterone

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Vitamin E modulates androgen receptor gene expression to attenuate ovarian dysfunctions in a rat model of dehydroepiandrosterone-induced polycystic ovary

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Asian pacific Journal of Reproduction 2023年第2期12卷 81-89页

作者： Olugbemi T Olaniyan Ayobami Dare Charles O.Adetunji Gloria E.Okotie Joseph B.Dare Bosun M.Adigun Femi Adebayo Laboratory for Reproductive Biology and Developmental Programming Department of PhysiologyEdo University UzairueEdo StateNigeria Discipline of Physiology School of Laboratory Medicine and Medical SciencesCollege of Health SciencesUniversity of KwaZulu-NatalWestville CampusDurbanSouth Africa Applied Microbiology Biotechnology and Nanotechnology LaboratoryDepartment of MicrobiologyEdo University UzairueEdo StateNigeria Department of Physiology University of IbadanIbadanNigeria Department of Anatomy Osun State University OshogboNigeria Department of Physiology Bingham UniversityNasarawa StateNigeria

Objective:To investigate the protective effect of vitamin E in dehydroepiandrosterone(DHEA)-induced polycystic ovary in ***:Premature female Wistar rats were randomly allocated into four groups,with 7 rats in each ***栺received corn oil(vehicle)and served as the control group;group栻received 0.2 mL of 0.06 mg/g DHEA in corn oil;group栿received 200 mg/kg vitamin E;group桇received DHEA plus vitamin *** treatments lasted for 15 days,with DHEA administered subcutaneously,while vitamin E and corn oil were administered *** the experiment,serum samples and ovaries were harvested for biochemical,immunohistochemical,hormonal,and histological *** ovarian mRNA expression of androgen receptor was analyzed by reverse transcriptase quantitative polymerase chain reaction(qPCR).Results:The antioxidant and metabolic enzyme activity significantly decreased in the DHEA-treated rats compared to the control rats(P<0.05).Administration of vitamin E to DHEAtreated rats significantly decreased cytokines and malondialdehyde compared to the DHEA-treated *** histological analysis showed reduced atretic and cystic ovaries,increased E-cadherin and Bcl-2 expression,and reduced expression of Bax in the DHEAtreated rats co-treated with vitamin *** mRNA expression of androgen receptor was upregulated in the DHEA-treated rats compared to the control ***:Vitamin E ameliorates the hyperandrogenic effect of DHEA-induced polycystic ovaries via metabolic,antioxidant,and anti-apoptotic pathways.

关键词： dehydroepiandrosterone Metabolic markers Polycystic ovarian syndrome Vitamin E Wistar rats

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Heyan Kuntai capsule versus dehydroepiandrosterone in treating Chinese patients with infertility caused by diminished ovarian reserve： a multicenter, randomized controlled trial

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Journal of Traditional Chinese Medicine 2017年第4期37卷 530-537页

作者： Gao Hui Xia Tian Ma Ruihong Zhao Zhimei Song Xueru Wang Baojuan Liu Lijing Han Kaimei Wang Guoqing Fu Yu Hao Guimin Department of Traditional Chinese Medicine Affiliated Hospital of Chengde Medical College Chengde 067000 China Department of Reproductive Center First Teaching Hospital of Tianjin University of Traditional Chinese Medicine Tianjin 300193 China Department of Reproductive center Tianjin Medical University General Hospital Tianjin 300052 China Graduate School Tianjin University of Traditional Chinese Medicine Tianjin 300193 China Department of Acupuncture First TeachingHospital of Tianjin University of TCM Tianjin 300193 China Department of Reproductive Center The Second Hospital of Hebei Medical University Shijiazhuang 050000 China

OBJECTIVE: To evaluate the clinical efficacy and safety of Heyan Kuntai capsule(HYKT) in treating women with infertility caused by diminished ovarian reserve(DOR).METHODS: One hundred eight eligible patientsfrom three Chinese hospitals were randomly divided into an HYKT treatment group(n = 55) or a dehydroepiandrosterone(DHEA) treatment group(n =53). Patients in the HYKT group were treated orally with four 0.5 g HYKT three times a day; patients in the DHEA group were treated with one 25.0 mg DHEA capsule three times a day. All patients were treated for 3 months and followed up over a3-month ***: Of 108 patients, 12 dropped out: six from the HYKT group, and six from the DHEA group. Eleven patients got pregnant during the treatment. Serum anti-Müllerian hormone levels and antral follicle counts increased significantly in both groups after treatment(P < 0.05) especially in the HYKT group(P < 0.05). Serum follicle stimulating hormone(FSH) levels and FSH/luteinizing hormone ratios decreased(P < 0.05) with no significant difference between the two groups. Estradiol levels in the HYKT group and DHEA-sulfate levels in the DHEA group both increased(P < 0.05). The spontaneous pregnancy rates were 12% and 11% in the HYKT and DHEA groups, respectively(not significant). During the follow-up period, 16 patients in the HYKT group underwent in vitro fertilization-embryo transfer(IVF-ET) and the number of retrieved oocytes was(5.1 ± 1.8). In DHEA group, 20 patients underwent IVF-ET and the number of retrieved oocyte was(4.2 ± 1.9)(not significant); clinical pregnancy rates were 38% in the HYKT group and 20%in DHEA group(not significant). No significant adverse reactions were ***: HYKT can improve the ovarian re-serve and hormone levels in patients with infertility caused by DOR. Pregnancy rates after HYKT treatment were similar to those of DHEA *** might be an alternative to the treatment of infertility caused by DOR.

关键词： Infertility, female Ovarian reserve Hormones dehydroepiandrosterone Heyan Kuntai capsule Randomized controlled trial

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Effects of dehydroepiandrosterone on Embryo Quality and Follicular Fluid Markers in Patients with Diminished Ovarian Reserves

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Reproductive and Developmental Medicine 2017年第1期1卷 1-8页

作者： Jing Fu Hua-Feng Jiang Lu Li Ai-Jie Xin Yi-Juan Sun Xiao-Xi Sun Shanghai Ji Ai Genetics and IVF Institute Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China Shi Men Second Road Community Health Service Center of Jingan District Shanghai 200041China Key Laboratory of Female Reproductive Endocrine Related Diseases Obstetrics and Gynecology HospitalFudan UniversityShanghai 200011China

Background:To examine the effects of dehydroepiandrosterone(DHEA)on in vitro fertilization(IVF)intracytoplasmic sperm injection(ICSI)and the levels of follicular fluid(FF)markers,namely,anti-Müllerian hormone(AMH),insulin-like growth factor(IGF)-1,bone morphogenetic protein(BMP)-15,and growth differentiation factor(GDF)-9,in patients with diminished ovarian reserves(DORs).Methods:116 patients with DOR were randomized into two groups,DHEA group and control *** group contained 58 *** DHEA group received 75 mg/d of DHEA for 12 weeks prior to the start of IVF treatment,while the control group entered IVF treatment *** patients were treated with the same ovarian stimulation *** primary outcome was high-quality embryo *** IVF parameters,such as the clinical pregnancy rate,embryo survival rate,and intact blastomere rate,were compared between the two *** samples from patients of both groups were collected to measure the levels of AMH,IGF-1,DHEA-sulfate,BMP-15,and *** was also collected on day 3 of the menstrual cycle to define the baseline hormonal profile and to examine ovarian reserve ***:The high-quality embryo yield was higher in DHEA group than that in control group(P=0.033).AMH and IGF-1 concentrations in FF were significantly higher in DHEA group than that in the control group(2.83±1.14 ng/L vs.1.37±0.55 ng/L,P=0.000;94.02±38.28 ng/L vs.74.03±25.46 ng/L,P=0.004,respectively).The BMP-15 level was also higher in DHEA group(relative expression were 1.80±0.41)than that in control group(relative expression were 0.79±0.16,P0.05)and in the clinical pregnancy rate between the two groups(13.79%vs.7.27%,respectively,P>0.05).Conclusions:In women with DOR undergoing IVF treatment,pretreatment with DHEA may increase the number of high-quality embryos,which may be due

关键词： Bone Morphogenetic Protein‑15 dehydroepiandrosterone Diminished Ovarian Reserve In vitro Fertilization

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dehydroepiandrosterone suppressing the ovariectomy-induced expansion of CD4+ T cells and TNF-α production to ameliorating bone phenotype not via converted to 17-β-estradiol in mice

Dehydroepiandrosterone suppressing the ovariectomy-induced e...

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第十届全国免疫学学术大会

作者： ling wang Dajin Li Laboratory for Reproductive Immunology Hospital & Institute of Obstetrics and Gynecology IBSFudan University Shanghai Medical College

Postmenopausal osteoporosis(PMO) has been recognized as an inflammatory condition. CD4

关键词： dehydroepiandrosterone postmenopausal osteoporosis CD4+ T cells TNF-α

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dehydroepiandrosterone sulfate supplementation in health and diseases

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World Journal of Meta-Analysis 2023年第4期11卷 102-111页

作者： Parth Jethwani Ashu Rastogi Ravindra Shukla Department of Endocrinology&Metabolism All India Institute of Medical Sciences JodhpurJodhpur 342001RajasthanIndia Department of Endocrinology Postgraduate Institution of Medical education and Research ChandigarhChandigarh 160017ChandigarhIndia

dehydroepiandrosterone sulfate(DHEAS)is a hormone produced by the zona reticularis of the adrenal gland and the *** considered as an inert compound merely serving as an intermediate in the conversion of cholesterol to androgens,interest in DHEA began to grow in the 1960s when it was found that DHEAS is the most abundant steroid hormone in human plasma and that its levels decline with *** many countries,DHEA is considered a nutritional *** has been used for a multitude of conditions which include sexual dysfunction,infertility,genitourinary syndrome of menopause,musculoskeletal disorders,cardiovascular diseases,ageing,neurological diseases,autoimmune conditions,adrenal insufficiency,and anorexia *** describe an overview of the historical evolution of DHEA,its physiology,and the disease states where it has been evaluated as a supplement.

关键词： dehydroepiandrosterone Adrenal Health supplements Hypothyroidism Autoimmunity Depression Cardiovascular disease

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<i>In-Vitro</i>Determination of Biological and Anabolic Functions of Weak Androgen dehydroepiandrosterone (DHEA) Using a Variety of Cell Lines

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Open Journal of Endocrine and Metabolic Diseases 2015年第8期5卷 105-116页

作者： James L. Cox Yingzi Chang Pandurangan Ramaraj Department of Biochemistry Kirksville College of Osteopathic Medicine A.T. Still University of Health Sciences Kirksville MO USA Department of Pharmacology Kirksville College of Osteopathic Medicine A. T. Still University of Health Sciences Kirksville MO USA

dehydroepiandrosterone (DHEA) is a weak androgen and is shown to have anti-cancer, anti-atherogenic, anti-adipogenic and anti-inflammatory effects on mouse, rat and rabbit models. However, human clinical trials data did not support animal findings and were inconclusive. These systemic differences in biological actions between rodents and humans were attributed to the low level of DHEA in rodents. In order to further understand the differences in biological functions between rodents and humans, we resorted to an in-vitroapproach involving mouse, rat and human cell lines to assess DHEA biological and anabolic functions separately and independently without systemic influence. Results indicated that DHEA was effective on mouse and rat cell lines but not on human cell lines, as observed in in-vivo studies. In addition, our in-vitrostudy showed that DHEA was able to induce myogenesis in mouse mesenchymal cells revealing its anabolic function, even though DHEA was considered as a weak androgen. This observation lent credence to the ban on DHEA by IOC medical commission, citing DHEA as an anabolic steroid. These in-vitro experiments suggested that the differences in biological actions of DHEA between rodents and humans existed not only in-vivo at the systemic level, but also in-vitro at the cellular level and thus paving the way to study the mechanism responsible for these differences at the cellular level itself.

关键词： dehydroepiandrosterone Various Cell Lines Biological Functions Anabolic Function

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