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Resveratrol Modulates Bone Mineral Density and Bone Mineral Content in A Rat Model of male hypogonadism

Chinese Journal of Integrative Medicine 2023年第2期29卷 146-154页

作者： Hussein F.Sakr Boudaka Ammar Amira AlKharusi I Al-Lawati Mahmoud AlKhateeb Basim H Elesawy Department of Physiology College of Medicine and Health SciencesSultan Qaboos UniversityMuscat 123Oman Medical Physiology Department Faculty of MedicineMansouraUniversityMansoura 35516Egypt Basic Medical Sciences Department College of Medicine at King Saud bin Abdulaziz University for Health Sciences(KSAU-HS)Riyadh 11481Saudi Arabia Department of Clinical Laboratory Sciences College of Applied Medical SciencesTaif UniversityTaif 21944Saudi Arabia

Objective: To determine whether resveratrol(Res) can correct osteoporosis induced in a rat model of male hypogonadism. Methods: Thirty-two rats were randomly divided into 4 groups, 8 in each group;1) a control sham group: underwent a similar surgical procedure for induction of orchiectomy(ORCD) without ligation of any arteries or veins or removal of the testis and epididymis;2) a control + Res-treated group(Con+Res):underwent sham surgery similar to the control, but was then treated with Res, as described below;3) an ORCDinduced group: bilateral ORCD surgery as described above, and 4) a ORCD+Res-treated group: bilateral ORCD surgery followed by Res treatment. Res treatment began 4 weeks after ORCD and continued for 12 weeks. After 12 weeks, bone mineral density(BMD) and bone mineral content(BMC) were measured in the tibia and femur of each rat’s right hind leg. Blood levels of bone turnover indicators such as deoxypyridinoline(Dpd), N-telopeptide of type Ⅰ collagen(NTXⅠ), alkaline phosphatase(ALP), and osteocalcin(OC), as well as receptor activator of nuclear factor kappa B(RANK) and osteoprotegerin(OPG) were assessed. Results: ORCD significantly decreased BMD(Pmale hypogonadism, possible via restoration of the normal balance between RANK and OPG.

关键词： osteoporosis male hypogonadism resveratrol receptor activator of nuclear factor-kappa

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Secondary male hypogonadism： a prevalent but overlooked comorbidity of obesity

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Asian Journal of Andrology 2018年第6期20卷 531-538页

作者： Maria Molina-Vega Araceli Mufioz-Garach Miguel Damas-Fuentes JosO Carlos Fernfindez-Garcia Francisco J inahones Department of Endocrinology and Nutrition Virgen de la Victoria Universitary HospitalMalaga 29010Spain Institute of Biomedical Research in Malaga（IBIMA） Virgen de la Victoria Universitary HospitalMalaga 29010Spain CIBER Pathophysiology of Obesity and Nutrition（CB06/003） Institute of Health Carlos III（ISClII）Madrid 28029Spain.

male hypogonadism associated with obesity is a very prevalent condition and is increasing in parallel with the epidemic prevalence of obesity. Low testosterone levels promote higher fat mass with reduced lean mass. male hypogonadism is related to an increase in associated cardiometabolic complications, such as hypertension, type 2 diabetes mellitus, the metabolic syndrome, and cardiovascular disease. Its influence as a comorbidity of obesity is becoming more evident and should be evaluated and treated in at-risk patients. Mechanisms involved in this relationship include body composition changes, the presence of adipokines, insulin resistance, and other factors, some of which are still unknown. Weight loss and treatment to replace testosterone levels improve the metabolic profile and quality of life in patients with obesity and hypogonadism; these beneficial effects depend on treatment modality and duration of therapy. The use of testosterone replacement therapy may be indicated, as it has not been shown to increase cardiovascular risk, and retrospective studies suggest a reduction in events in men with metabolic syndrome and type 2 diabetes.

关键词： adipose tissue male hypogonadism obesity testosterone

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Effects of velvet antler polypeptide on sexual behavior and testosterone synthesis in aging male mice

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Asian Journal of Andrology 2016年第4期18卷 613-619页

作者： Zhi-Jun Zang Hong-Feng Tang Ying Tuo Wei-Jie Xing Su-Yun Ji Yong Gao Chun-Hua Deng Department of Infertility and Sexual Medicine The Third Affiliated Hospital Sun Yat-sen University Guangzhou China Department of Dermatology Shunde First People's Hospital Affiliated to Southern Medical University Foshan China Department of Histopathology The First Affiliated Hospital Sun Yat-sen University Guangzhou China Center for Reproductive Medicine The Third Affiliated Hospital Sun Yat-sen University Guangzhou China Department of Dermatology Guangdong Provincial Dermatology Hospital Guangzhou China Reproductive Medicine Centre and Guangdong Provincial Key Laboratory of Reproductive Medicine The First Affiliated Hospital Sun Yat-sen University Guangzhou China Department of Urology The First Affiliated Hospital Sun Yat-sen University Guangzhou China

Twenty-four-month-old male C57BU6 mice with low serum testosterone levels were used as a late-onset hypogonadism （LOH） animal model for examining the effects of velvet antler polypeptide （VAP） on sexual function and testosterone synthesis. These mice received VAP for 5 consecutive weeks by daily gavage at doses of 100, 200, or 300 mg kg-1 body weight per day （n = 10 mice per dose）. Control animals （n = 10） received the same weight-based volume of vehicle. Sexual behavior and testosterone levels in serum and interstitial tissue of testis were measured after the last administration of VAP. Furthermore, to investigate the mechanisms of how VAP affects sexual behavior and testosterone synthesis in vivo, the expression of steroidogenic acute regulatory protein （STAR）, cytochrome P450 cholesterol side-chain cleavage enzyme （P450scc）, and 3β-hydroxysteroid dehydrogenase （3βHSD） in Leydig cells was also measured by immunofluorescence staining and quantitative real-time PCR. As a result, VAP produced a significant improvement in the sexual function of these aging male mice. Serum testosterone level and intratesticular testosterone （ITT） concentration also increased in the VAP-treated groups. The expression of STAR, P450scc, and 3β-HSD was also found to be enhanced in the VAP-treated groups compared with the control group. Our results suggested that VAP was effective in improving sexual function in aging male mice. The effect of velvet antler on sexual function was due to the increased expression of several rate-limiting enzymes of testosterone synthesis （STAR, P450scc, and 3β-HSD） and the following promotion of testosterone syothesis in vivo.

关键词： aged male hypogonadism mouse sexual behavior testosterone synthesis velvet antler polypeptide

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Androgen receptor deficiency in monocytes/ macrophages does not alter adiposity or glucose homeostasis in male mice

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Asian Journal of Andrology 2018年第3期20卷 276-283页

作者： Katya B Rubinow Barbara Houston Shari Wang Leela Goodspeed Kayoko Ogimoto Gregory J Morton Christopher McCarty Robert E Braun Stephanie T Page Division of Metabolism Endocrinology and Nutrition Department of Medicine University of Washington School of Medicine Seattle WA 98195 USA Jackson Laboratory Bar Harbor ME 04609 USA

Androgen deprivation in men leads to increased adiposity, but the mechanisms underlying androgen regulation of fat mass have not been fully defined. Androgen receptor （AR） is expressed in monocytes/macrophages, which are resident in key metabolic tissues and influence energy metabolism in surrounding cells. male mice bearing a cell-specific knockout of the AR in monocytes/macrophages （M-ARKO） were generated to determine whether selective loss of androgen signaling in these cells would lead to altered body composition. Wild-type （WT） and M-ARKO mice （12-22 weeks of age, n = 12 per group） were maintained on a regular chow diet for 8 weeks and then switched to a high-fat diet for 8 additional weeks. At baseline and on both the regular chow and high-fat diets, no differences in lean mass or fat mass were observed between groups. Consistent with the absence of differential body weight or adiposity, no differences in food intake （3.0 ± 0.5 g per day for WT mice vs 2.8 ± 0.4 g per day for M-ARKO mice） or total energy expenditure （0.6 ± 0.1 Kcal h-1 for WT mice vs 0.5 ± 0.1 Kcal h-1 for M-ARKO mice） were evident between groups during high-fat feeding. Liver weight was greater in M-ARKO than that in WT mice （1.5 ± 0.1 g vs 1.3 ± 0.0 g, respectively, P = 0.02）. Finally, M-ARKO mice did not exhibit impairments in glucose tolerance or insulin sensitivity relative to WT mice at any study time point. In aggregate, these findings suggest that AR signaling specifically in monocytes/macrophages does not contribute to the regulation of systemic energy balance, adiposity, or insulin sensitivity in male mice.

关键词： androgen receptor knockout mice macrophages male hypogonadism metabolic syndrome

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Testicular ultrasound inhomogeneity is an informative parameter for fertility evaluation

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Asian Journal of Andrology 2020年第3期22卷 302-308页

作者： Giorgia Spaggiari Antonio R M Granata Daniele Santi Unit of Endocrinology Department of BiomedicalMetabolic and Neural SciencesUniversity of Modena and Reggio EmiliaModena 41126Italy Unit of Endocrinology Department of Medical SpecialtiesAzienda Ospedaliero-Universitaria of ModenaOspedale Civile of BaggiovaraModena 41126Italy.

Testicular volume(TV)is proposed to be a positive predictor of male fertility status,because of the relation known between the TV and the seminiferous tubule *** of the measurement methodology,the role of TV and testicular ultrasound(US)assessments is still debated in andrological clinical *** this retrospective cohort study,we evaluated TV and testis US role in the diagnostic workup of andrological *** consecutive outpatients undergoing single-operator testis US(Modena,Italy)from March 2012 to March 2018 were enrolled,matching sonographic,hormonal,and seminal data.A total of 302 men were referred and evaluated for gynecomastia,suspected hypogonadism,couple infertility(Cl),or sexual *** the hypogonadal group,TV was lower compared to that in other groups(P<0.001),and a significant,direct correlation between TV and testosterone level was observed in nonandrogen-treated patients(R=0.911,P<0.001),suggesting that testicular size could be related to the testosterone-secreting *** the Cl group,normozoospermic patients showed higher TV compared to men with impaired semen quality(P=0.003)and azoospermia(P=0.003).However,TV was not able to discriminate between patients presenting normal and altered semen *** the contrary,testis US inhomogeneity was more frequent in patients with impaired sperm quality(55.0%;P=0.007)and azoospermia(40.0%;P=0.012),compared to patients with normozoospermia(5%),identifying thereby the sonographic pattern as an informative parameter of the fertility ***,in the Cl workup,US evaluation seems to be more informative than the TV assessment alone.

关键词： male hypogonadism male infertility testicular diseases testis

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Androgens and prostate disease

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Asian Journal of Andrology 2014年第2期16卷 248-255,I0009页

作者： Lori A Cooper Stephanie T Page Departments of Medicine Division of Endocrinology and Metabolism University of Washington Seattle University of Washington and Harborview Medical Center Seattle Washington USA.

A growing body of literature has established the anabolic benefits of testosterone （T） therapy in hypogonadal men. However, there remains a paucity of data regarding the risks of exogenous androgen use in older men and the potential for adverse effects on the prostate gland. Whether T therapy in older, hypogonadal men might worsen lower urinary tract symptoms or exacerbate, unmask, or even incite prostate cancer development has tempered enthusiasm for T therapy, while known prostatic disease has served as a relative contraindication to T therapy. Androgens are necessary for the development and maintenance of the prostate gland. However, epidemiologic studies do not consistently find a positive relationship between endogenous serum androgen concentrations and the risk of prostate disease. Recent data demonstrate that 5α-reductase inhibitors decrease the risk of low-grade prostate cancer, suggesting that modifying androgen metabolism may have beneficial effects on prostate health, yet similar reductions in high-grade disease have not been observed, thereby questioning the true clinical benefits of these agents for chemoprevention. Knowing how to best investigate the relationship between androgens and the development of prostate disease given the lack of large, randomized trials is difficult. Accumulating data challenges the assumption that alterations in serum androgens have parallel effects within the prostate hormonal environment or change androgen-regulated processes within the gland. Long-term intervention studies are needed to truly ascertain the effects of androgen manipulation on prostate tissue and disease risk. However, available data do not support the notion that restoring serum androgens to normal physiologic ranges drives prostate disease.

关键词： androgens male hypogonadism prostate testosterone

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How to recognize late-onset hypogonadism in men wit sexual dysfunction

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Asian Journal of Andrology 2012年第2期14卷 251-259页

作者： Giovanni Corona Giulia Rastrelli Linda Vignozzi Edoardo Mannucci Mario Maggi Sexual Medicine and Andrology Unit Department of Clinical Physiopathology University of Florence Florence 50139 Italy Endocrinology Unit Maggiore-Bellaria Hospital Medical Department Azienda-Usl Bologna Bologna 40133 Italy Diabetes Section Geriatric Unit Department of Critical Care University of Florence Florence 50139 Italy

Late-onset hypogonadism （LOH） has been considered the most common form of male hypogonadism with a prevalence of approximately 1 in 100 men. Diagnosis of LOH should be made in symptomatic men with unequivocally low serum testosterone （T） levels. However, its clinical presentation is often insidious and difficult to recognize because it is characterized by nonspecific symptoms that make differential diagnosis with physiological ageing problematic. Sexual dysfunction is the most important determinant for medical consultation and the most specific symptom associated with low T. We therefore analysed a consecutive series of 1734 subjects who attended our unit for sexual dysfunction to investigate the associations between low T （different thresholds）, sexual parameters, medical history data （delayed puberty, pituitary disease or cryptorchidism） and their physical exam results. Metabolic parameters, in particular waist circumference, display the greatest accuracy in detecting low T. We found that only the association of several symptoms and signs could significantly raise the clinical suspicion of low T. Structured inventories, which cluster together symptoms and signs of hypogonadism, can help clinicians suspect androgen deficiency. In particular, structured interviews, such as ANDROTEST, have been demonstrated to have a greater accuracy when compared to self reported questionnaires in detecting low T levels.

关键词： late-onset hypogonadism (LOH) male hypogonadism testosterone sexual dysfunction

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Apoptotic Sertoli cell death in hypogonadic(hgn/hgn)rat testes during early postnatal development

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Asian Journal of Andrology 2006年第5期8卷 535-541页

作者： MioYagi KatsushiSuzuki HirotesuSuzuki Department of Veterinary Physiology Nippon Veterinary and Life Science UniversityTokyo 180-8602Japan

Aim： To determine the involvement of apoptotic cell death in postnatal pathogenesis in mutant strain of hypogonadic （hgn/hgn） rats testes. We evaluated the numbers and types of cells undergoing apoptotic cell death. Methods： Tissue sections were stained by the TUNEL method for in situ detection of apoptotic cells, with specific antibodies used as markers of testicular somatic and germ cells. Results： We found that apoptosis in the hgn/hgn testes during the early postnatal period occurred primarily in Sertoli cells, which should actively proliferate during this stage of differentiation. These findings strongly suggest that the normal allele of hgn is involved in the direct or indirect control of differentiation and proliferation of Sertoli cells. Conclusion： To our knowledge, this is the first report demonstrating early postnatal apoptosis of Sertoli cells, suggesting that the hgn/hgn rat is a unique model for the study of Sertoli cell deficiency.

关键词： apoptosis hgn/hgn male hypogonadism Sertili cell testis TUNEL vimentin

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Bone mineral density in hypogonadal men remains low after long—term testosterone replacement

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Asian Journal of Andrology 2002年第2期4卷 117-121页

作者： KazuhiroIshizaka MashitoSuzuki 等 DepartmentofUrology KantoCentralHospitalTokyo158－8531Japan DepartmentofUrologyandReproductionTokyoMedicalandDentalUniversity

AIM:In 11 congenital hypogonadal men, the bone mineral density (BMD) values were determined to assess the effect of long-term androgen replacement therapy (ART) on skeletal integrity.METHODS:Eleven congenital hypogonadal men, including 8 isolated gonadotropin deficiency patients, 2 Kallmann's syndrome and 1 vanishing testes syndrome were recruited and treated with 250 mg of testosterone enanthate intramuscularly every 4 weeks for 7-43 years (mean+/-SD: 21.5 +/-13 years). In these patients and a group of 10 healthy young men (controls), the whole and trabecular BMDs were examined at the distal end of radius by means of a peripheral quantitative computerized tomography device.RESULTS:The whole radial BMD in hypogonadal men was significantly less in the patients than in the healthy men (498+/-115 and 725+/-134 mg/cm(3), respectively; P<0.01); the trabecular BMD was also lower in the hypogonadal men (199+/-80 and 375+/-89 mg/cm(3); P< 0.01). The whole radial BMD values in 10 of 11 hypogonadal men were at least 1 SD below the mean value for healthy young men; 2 hypogonadal men had BMD values more than 2.5 SD lower than the healthy mean. Additionally, the whole radial BMD showed a significant negative correlation with the patient's age at the initiation of ART (r = 0.748, P<0.01). The serum level of bone-specific alkaline phosphatase and the urinary level of deoxypyridinoline were not significantly different between the two groups.CONCLUSION:Osteopenia persists in the hypogonadal men after long-term ART, suggesting that such patients have a persistent defect in bone development not alleviated by androgen replacement.

关键词： Androgen replacement therapy Bone mineral density male hypogonadism

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Leydig cell transplantation restores androgen production in surgically castrated prepubertal rats

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Asian Journal of Andrology 2009年第4期11卷 405-410页

作者： Jie Sun Ye-Bin Xi Zhong-De Zhang Ping Shen Huai-Yuan Li Min-Zhi Yin Wei-Yi Li Cheng-Ren Shi Department of Urology Shanghai Children＇s Medical Center Shanghai 200127 China Department of Immunology Shanghai Jiao Tong University School of Medicine Shanghai 200025 China Department of Pathology Shanghai Children＇s Medical Center Shanghai 200127 China Department of Clinical Laboratory Shanghai Children＇s Medical Center Shanghai 200127 China Department of Pediatric Surgery Xin Hua Hospital Shanghai Jiao Tong University Shanghai 200092 China

Prepubertal testicular dysfunction and the subsequent development of hypogonadism affects an estimated one in 200 children worldwide. As the testosterone levels are dynamic during development and puberty, traditional hormone treatment regimens are often inadequate, thereby leaving associated physiological conditions unresolved. Therefore, we have investigated the potential therapeutic effect of mature Leydig cell transplantation for the treatment of prepubertal primary hypogonadism through the use of a surgically induced hypogonadistic rat model system. In the experiment, Leydig cells were surgically isolated from mature Sprague-Dawley rats and transplanted into prepubertal recipients. Serum testosterone levels and microscopic analysis of the stained testicular interstitium were compared with sham-treated controls, as well as with castrated and intact rats during sexual development. At 4 weeks post-implantation, serum testosterone was detectable in Leydig cell recipients, but not in surgical controls, and progressively increased as a function of time until reaching levels comparable with sexually mature males at 12 weeks post-implantation. Histological analysis revealed a high rate of Leydig cell survival as well as steroidogenic secretory activity. Therefore, we conclude that mature Leydig cell transplantation in prepubertal hypogonadism recipients has therapeutic potential in rats and merits further investigation for clinical application.

关键词： androgens Leydig cells male hypogonadism testis

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