Journal Of Andrology[JOURNAL]
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200 papers
Special Section: Commemorating the Journal of Andrology's Distinguished History.
Burnett AL, Darney SP, Sandlow J
J Androl · 2012 · PMID 22879532 · Publisher ↗
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Parting messages from current and former editors of the Journal of Andrology.
Bartke A, Orgebin-Crist MC, Desjardins C … +9 more , Lewis R, Tindall D, Hamilton DW, Pryor JL, Schlegel PN, Hardy MP, Burnett AL, Darney SP, Sandlow J
J Androl · 2012 · PMID 22879531 · Publisher ↗
The proposal to produce this final commemorative issue for the Journal of Andrology arose during our regular discussions as current editors soon after it was announced that the Journal would complete its own life course...
The proposal to produce this final commemorative issue for the Journal of Andrology arose during our regular discussions as current editors soon after it was announced that the Journal would complete its own life course and merge into a new publication (to be named Andrology) with the International Journal of Andrology. We considered the momentous occasion to be one that should be celebrated with an enduring tribute in recognition of the Journal's exceptional 33-year existence. Among the various contributions sought for inclusion in this issue, we envisioned an article assembling collected short essays from all living former editors drawing on notable events and highlights, if not less well-known challenges and successes arising during their editorship eras. We thought that any such production of musings, viewpoints, and most of all words of wisdom from those who have had major roles in the direction and accomplishments of the Journal would offer an illuminating read for the society's members and friends and provide all readers another venue to share in and enjoy the Journal's great history. We are enthralled to have gathered these collections, all personal compositions of the former editors-in-chief, and for their effort that has helped us complete this special endeavor we express to them our tremendous gratitude. Serving as the Journal's last editors, we are also grateful to contribute our essay at the very end as part of this joyous chronicle.
Evolution of the Journal of Andrology and a bright future for Andrology.
Meistrich ML, Carrell DT
J Androl · 2012 · PMID 22879530 · Publisher ↗
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Management of erectile dysfunction: great progress, greater promise.
Burnett AL, Hellstrom WJ
J Androl · 2012 · PMID 22879529 · Publisher ↗
Sexual medicine, exemplified by the management of erectile dysfunction, is a traditional pillar of andrology. Erectile dysfunction has received the greatest attention within the specialty area and its management models t...
Sexual medicine, exemplified by the management of erectile dysfunction, is a traditional pillar of andrology. Erectile dysfunction has received the greatest attention within the specialty area and its management models the progress of the field more generally. This review provides a perspective of the history and contemporary practice of erectile dysfunction management, highlighting aspects of basic science research, epidemiology, and clinical care. Furthermore, the impact of this field as a major health concern in correlation with basic aspects of wellness and disease is acknowledged. The field continues to evolve as a legitimate discipline in medicine and is worthy of ongoing scientific support and activity.
Aging and declining testosterone: past, present, and hopes for the future.
Zirkin BR, Tenover JL
J Androl · 2012 · PMID 22879528 · Full text
As men age, serum testosterone (T) levels decline, whereas serum luteinizing hormone (LH) levels increase somewhat or remain unchanged. Age-related reductions in T levels may be associated with alterations in body compos...
As men age, serum testosterone (T) levels decline, whereas serum luteinizing hormone (LH) levels increase somewhat or remain unchanged. Age-related reductions in T levels may be associated with alterations in body composition; energy level; muscle strength; physical, sexual, and cognitive functions; and mood. The predominant contributor to the decline in serum T levels is the decreased ability of the aging testes to make T. As in humans, the Brown Norway rat demonstrates age-related reductions in serum T levels in the setting of unchanged or modestly increased serum LH levels. In this rat model, the ability of aged Leydig cells, the terminally differentiated T-producing cells of the testis, to produce T in response to LH stimulation is significantly diminished. This review begins with a discussion of what is known of the molecular mechanisms by which T synthesis declines with Leydig cell aging. It concludes with a brief history of T replacement therapy, current guidelines, controversies related to T replacement therapy in older men, and proposed future clinical directions.
The genetics of male fertility--from basic science to clinical evaluation.
Pastuszak AW, Lamb DJ
J Androl · 2012 · PMID 22879527 · Publisher ↗
Our understanding of male fertility has increased dramatically over the past several decades, in large part because of advances in technology and the ability to rapidly analyze large quantities of high-resolution genetic...
Our understanding of male fertility has increased dramatically over the past several decades, in large part because of advances in technology and the ability to rapidly analyze large quantities of high-resolution genetic data. These research efforts have led to an understanding of some of the genes involved in male fertility and have enabled us to test for defects in these genes that result in infertility in men. However, our understanding of male fertility remains far from comprehensive, and many genes involved in male fertility likely remain to be identified and their mechanisms of action elucidated. This can only be accomplished through continued, persistent investigations using cutting-edge technologies. In this review, we discuss the history of genetic testing and how it applies to male fertility, from the identification of the sex chromosomes at the turn of the century to classification of single-nucleotide polymorphisms that may result in infertility and are the crux of modern genetic analysis. We discuss the genetic testing methodologies traditionally used for genetic assessment of infertile males, including karyotype analysis, sperm fluorescence in situ hybridization, and polymerase chain reaction-based testing for Y chromosomal evaluation, as well as cutting-edge genetic testing methodologies using microarrays and whole-genome sequencing, permitting analysis at a nucleotide-level resolution. Finally, we describe our vision of the future of genetic testing in the setting of male infertility, culminating in truly personalized medicine for each affected infertile male.
Questions about spermatogonia posed and answered since 2000.
de Rooij DG, Griswold MD
J Androl · 2012 · PMID 22879526 · Publisher ↗
This review focuses on 3 important advances in our understanding of rodent spermatogonial stem cells (SSC) that have emerged since 2000: the identity of SSC, the existence of a SSC niche, and gene expression in spermatog...
This review focuses on 3 important advances in our understanding of rodent spermatogonial stem cells (SSC) that have emerged since 2000: the identity of SSC, the existence of a SSC niche, and gene expression in spermatogonia. It is now apparent that the original scheme, in which the A(single) (A(s)) spermatogonia are the only stem cells, may be too simple. Rather, separation of pairs of A(paired) (A(pr)) spermatogonia into singles might also play a role in the steady state situation. However, evidence that in the normal epithelium fragmentation of chains of A(aligned) (A(al)) spermatogonia into smaller clones also plays a role is not yet conclusive. New evidence presented during the last decade indicates that the A(s),A(pr), and A(al) (A(s,pr,al)) spermatogonia are not localized at random over the tubule basal lamina, as originally assumed, but are restricted to those areas that border on interstitial tissue and, in particular, to areas containing venules and arterioles, suggesting a specific relationship of this localization with a possible SSC niche. Finally, gene expression studies are showing how both extrinsic factors produced by Sertoli cells and intrinsic factors that are products of the germ cells act either to maintain progenitor cells or to promote differentiation and the commitment to meiosis. Taken together, this new knowledge adds to our understanding of the balance between 2 opposing forces: one promoting the undifferentiated state and the other promoting the commitment to meiosis and differentiation that is essential for spermatogenesis to proceed.
Reactive oxygen species and sperm function--in sickness and in health.
Aitken RJ, Jones KT, Robertson SA
J Androl · 2012 · PMID 22879525 · Publisher ↗
The ability of spermatozoa to generate reactive oxygen species (ROS) has been appreciated since the 1940s. It is a universal property of mature spermatozoa from all mammalian species and a major contributor to the oxidat...
The ability of spermatozoa to generate reactive oxygen species (ROS) has been appreciated since the 1940s. It is a universal property of mature spermatozoa from all mammalian species and a major contributor to the oxidative stress responsible for defective sperm function. The mechanisms by which oxidative stress limits the functional competence of mammalian spermatozoa involve the peroxidation of lipids, the induction of oxidative DNA damage, and the formation of protein adducts. ROS production in these cells involves electron leakage from the sperm mitochondria, triggered by a multitude of factors that impede electron flow along the electron transport chain. The net result of mitochondrial ROS generation is to damage these organelles and initiate an intrinsic apoptotic cascade, as a consequence of which spermatozoa lose their motility, DNA integrity, and vitality. This pathway of programmed senescence also results in the exteriorization of phosphatidylserine, which may facilitate the silent phagocytosis of these cells in the aftermath of insemination, in turn influencing the female tract immune response to sperm antigens and future fertility. Despite the vulnerability of sperm to oxidative stress, it is also clear that normal sperm function depends on low levels of ROS generation in order to promote the signal transduction pathways associated with capacitation. Modulators of ROS generation by spermatozoa may therefore have clinical utility in regulating the fertilizing capacity of these cells and preventing the development of antisperm immunity. Achievement of these objectives will require a systematic evaluation of pro- and antioxidant strategies in vivo and in vitro.
The semen quality of 1158 men with testicular cancer at the time of cryopreservation: results of the French National CECOS Network.
Rives N, Perdrix A, Hennebicq S … +9 more , Saïas-Magnan J, Melin MC, Berthaut I, Barthélémy C, Daudin M, Szerman E, Bresson JL, Brugnon F, Bujan L
J Androl · 2012 · PMID 22837112 · Publisher ↗
Testicular cancer is the most common cancer in young men. Several studies have reported an alteration in semen quality in nonseminoma tumors, but this result has not been confirmed in all of the published data. We perfor...
Testicular cancer is the most common cancer in young men. Several studies have reported an alteration in semen quality in nonseminoma tumors, but this result has not been confirmed in all of the published data. We performed a retrospective study in a population of 1158 men with testicular cancer who banked sperm between 1999 and 2003 in 11 French Centre d'Etude et de Conservation des Oeufs et du Sperme humain laboratories. Our study evaluated prefreeze and postthaw sperm parameters according to patient medical history, tumor histological type, and disease stage. Pure seminomas were found in 48% of our population. Testicular cancer was generally diagnosed at stage I. In cases of a history of unilateral cryptorchidism, testicular cancer occurred preferentially in the maldescended testis. Semen samples were preferentially collected after orchiectomy. The sperm concentration and total sperm number were significantly lower before orchiectomy in seminomas compared with nonseminoma tumors (P < .001). After orchiectomy, these parameters decreased for nonseminoma tumors and did not vary for seminomas. Semen parameters were more severely impaired for stage III tumors, and when patients had a history of cryptorchidism or when they were less than 20 years of age. Azoospermia was more frequently observed before than after orchiectomy. In this study, we determined that sperm cryobanking should preferentially be performed before orchiectomy and that testicular sperm extraction concurrent with orchiectomy should be used in severe spermatogenesis impairment. Our study highlights that seminomas alter sperm production more significantly than nonseminoma tumors and seem to preferentially impair spermatogenesis in tumor-bearing testes.
Dietary fat modulates the testosterone pharmacokinetics of a new self-emulsifying formulation of oral testosterone undecanoate in hypogonadal men.
Yin A, Alfadhli E, Htun M … +8 more , Dudley R, Faulkner S, Hull L, Leung A, Bross R, Longstreth J, Swerdloff R, Wang C
J Androl · 2012 · PMID 22790645 · Full text
This study investigates the effect of dietary fat on the testosterone (T) pharmacokinetics in hypogonadal men following administration of a self-emulsifying capsule formulation of oral T undecanoate (TU). In an open-labe...
This study investigates the effect of dietary fat on the testosterone (T) pharmacokinetics in hypogonadal men following administration of a self-emulsifying capsule formulation of oral T undecanoate (TU). In an open-label, 2-center, 5-way crossover study, a single oral dose of TU containing 300-mg equivalents of T (maximum anticipated human dose per administration) was administered to 16 hypogonadal men with a washout period of at least 5 days between doses. All participants were randomized to receive the TU capsules fasting or 30 minutes after an approximately 800-calorie meal containing 10%, 20%, 30%, or 50% fat. Serial blood samples were collected from 2 hours predose to 25 hours postdose to determine serum T and dihydrotestosterone (DHT) by liquid chromatography tandem mass spectrometry. Administering TU with a meal increased serum T concentrations, with the magnitude of the increase being directly dependent on the amount of fat in the meal. Average and peak serum T concentrations and area under the curve increased as the fat content of the meal was increased. Neither the high-fat meal (50% fat) nor the lower-fat meal (20% fat) showed a significant food effect relative to the normal-fat (Western diet) meal (30% fat). However, administering TU while fasting resulted in 50% or less of the cumulative exposure obtained when administered with 20%- to 50%-fat meals (albeit still substantial). A very-low-fat meal (10% fat) showed a significant food effect relative to the normal meal, but still exceeded the fasting condition by approximately 50%. Serum DHT concentrations showed corresponding increases to the serum T. As expected with the maximum anticipated clinical dose of TU (300 mg T), oral administration of this new formulation with food containing 20% to 50% dietary fat produced T levels at or above the upper range of adult men, and T levels trended higher as dietary fat content increased. Only with a very-low-fat diet (10%) or in a fasted state did a clinically significant food effect occur, but even then sufficient TU was absorbed with the self-emulsifying TU formulation to produce average serum T concentration predicted to be in the normal reference range (10 to 35 nmol/L).
Effects of castration and late hormonal replacement in the structure of rat corpora cavernosa.
Miranda AF, Gallo CB, De Souza DB … +2 more , Costa WS, Sampaio FJ
J Androl · 2012 · PMID 22790644 · Publisher ↗
The objective of the study was to evaluate, through quantitative methods, the structural alterations in the corpora cavernosa of rats submitted to orchiectomy as well as the role of late hormone replacement in overturnin...
The objective of the study was to evaluate, through quantitative methods, the structural alterations in the corpora cavernosa of rats submitted to orchiectomy as well as the role of late hormone replacement in overturning the possible structural alterations. Twenty-five male rats were assigned into 5 groups with 5 animals each and treated as follows: ORCHIEC-1 = submitted to orchiectomy and sacrificed after 1 month; C-1 = control group sacrificed after 1 month; ORCHIEC-2 = submitted to orchiectomy and sacrificed after 2 months; C-2 = control group sacrificed after 2 months; and T = submitted to orchiectomy, underwent testosterone replacement with testosterone undecanoate (100 mg/kg) after 1 month, and sacrificed after 1 month of hormonal replacement. Smooth muscle, collagen, and elastic system fibers of penile corpora cavernosa were quantified. There was a significant decrease in the absolute values of smooth muscle, sinusoidal space, and total area of corpora cavernosa after 2 months in the castrated group when compared with controls. Overall, regarding density, no significant differences were observed among the groups. The hormonal replacement with testosterone was able to reverse the alterations observed. The method used for this research allowed demonstrating that absolute values are reliable to quantify the structural alterations of corpora cavernosa structures. The results suggest that hormonal replacement, even when instituted at a late stage, is effective in reversing the corpora cavernosa's structural alterations produced by castration.
Seasonal fluctuations in testosterone-estrogen ratio in men from the Southwest United States.
Moskovic DJ, Eisenberg ML, Lipshultz LI
J Androl · 2012 · PMID 22790643 · Publisher ↗
Although controversial, seasonal variations in testosterone have been observed in several populations of men throughout the world. This finding might have an impact on screening and treatment of hypogonadism. We examined...
Although controversial, seasonal variations in testosterone have been observed in several populations of men throughout the world. This finding might have an impact on screening and treatment of hypogonadism. We examined the circannual patterns of sex hormones in the Southwest United States. A prospectively assembled database of almost 11 000 patients in a men's health practice was used to collect data on testosterone, estradiol, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and dehydroepiandrosterone-sulfate (DHEA-S). Patient age, address, and date of visit were recorded. Of note, testosterone-estrogen ratio (T/E ratio) and free testosterone were calculated values. The data were grouped by month and by season (3-month intervals beginning with June, July, and August as summer). Analysis of variance was used to compare hormone levels between seasonal and monthly data sets, with P < .05 regarded as statistical significance. Statistically significant differences in estradiol (P = .02), T/E ratio (P < .01), FSH (P = .02), and SHBG (P < .01) were observed between seasons. Peak-to-trough variations were as follows: 6% for estradiol, 16.5% for T/E ratio, 11.0% for FSH, and 11.6% for SHBG. The T/E ratio peaked in the spring and was at its nadir in the fall. No differences in testosterone (P = .21), LH (P = .25), free testosterone (P = .08), and DHEA-S (P = .11) were observed. Statistically significant evidence of variation in estradiol and T/E ratio were identified in the men included in this study. Although this is consistent with seasonal body habitus changes, physical activity levels, and hypothesized hormonal patterns, the variability reported in the literature makes further trials covering a broader geographic region important to confirm the findings.
Effects of once-daily tadalafil on treatment satisfaction, psychosocial outcomes, spontaneous erections, and measures of endothelial function in men with erectile dysfunction but naive to phosphodiesterase type 5 inhibitors.
Porst H, Brock GB, Kula K … +5 more , Moncada I, Montorsi F, Basson BR, Kinchen K, Aversa A
J Androl · 2012 · PMID 22790642 · Publisher ↗
Previous studies established the efficacy of once-daily tadalafil for men with erectile dysfunction. However, no trial has focused on the effects of such treatment on men without previous experience using oral phosphodie...
Previous studies established the efficacy of once-daily tadalafil for men with erectile dysfunction. However, no trial has focused on the effects of such treatment on men without previous experience using oral phosphodiesterase type 5 inhibitors. Patients were randomized (2:1) to once-daily tadalafil 5 mg (with possible down-titration to 2.5 mg; n = 146) or placebo (n = 69) for 12 weeks. Among 215 patients (mean age, 52 years), once-daily tadalafil treatment resulted in 61.7% of study participants reporting their ability to achieve and maintain erections as being much better or very much better (vs 21.7% on placebo; P < .001). Tadalafil significantly improved treatment satisfaction on the Erectile Dysfunction Inventory of Treatment Satisfaction (P < .001 vs placebo at end point) and psychosocial outcomes on the Self-Esteem and Relationship (SEAR) questionnaire (least squares mean difference in SEAR total score change from baseline, 11.8 [95% confidence interval, 5.4%-18.2%; P < .001 vs placebo]). Patients receiving once-daily tadalafil also experienced a higher proportion of daily self-reported spontaneous morning erections at end point (58.7%) compared with placebo (42.2%; P < .001 for the between-treatment difference in changes from baseline). However, no significant differences in parameters of endothelial dysfunction (including biomarkers and peripheral arterial tonometric measures) or nocturnal erections as recorded by the nocturnal electrobioimpedance volumetric assessment were observed between treatment groups. Tadalafil was well tolerated; adverse events included back pain, headache, and dyspepsia. These findings may contribute to a more comprehensive understanding of once-daily tadalafil's effects on phosphodiesterase type 5 inhibitor-naive men.
Sexual dysfunction following radical prostatectomy.
Benson CR, Serefoglu EC, Hellstrom WJ
J Androl · 2012 · PMID 22744864 · Publisher ↗
Prostate cancer is the most common solid cancer in men and the second leading cause of cancer death in men. A favored treatment option for organ-confined prostate cancer in a middle-aged healthy man is radical prostatect...
Prostate cancer is the most common solid cancer in men and the second leading cause of cancer death in men. A favored treatment option for organ-confined prostate cancer in a middle-aged healthy man is radical prostatectomy (RP). Despite advances in techniques for RP, there remain concerns among physicians and patients alike on its adverse effects on sexual function. Although post-RP erectile dysfunction has been extensively studied, little attention has been focused on the other domains of sexual function, namely loss of libido, ejaculatory dysfunction, orgasmic dysfunction, penile shortening, and Peyronie disease. The aim of this review is to discuss the most recent literature regarding post-RP sexual dysfunctions.
Prognostic factors in Chinese patients with penile invasive squamous cell carcinoma.
Chen X, Li X, Garcia MM … +4 more , Gong K, Song Y, He Z, Zhou L
J Androl · 2012 · PMID 22744863 · Publisher ↗
The incidence of penile cancer varies by ethnicity and is not well described among Chinese patients. We performed a retrospective study to assess the prognostic factors in Chinese patients with penile invasive squamous c...
The incidence of penile cancer varies by ethnicity and is not well described among Chinese patients. We performed a retrospective study to assess the prognostic factors in Chinese patients with penile invasive squamous cell carcinoma (SCC). We reviewed the medical records of 83 consecutive patients treated at the National Urological Cancer Center (Beijing, China). The Kaplan-Meier method, log-rank test, and multivariate Cox proportional hazard model were used to identify the prognostic factors predicting for cancer-specific survival (CSS). Univariate and multivariate logistic regression analysis were used to analyze the predictive factors for lymph node metastasis (LNM). A total of 55 patients were followed. Twelve patients (20%) died from the disease during follow-up. By univariate analysis, older age (≥ 49 years; P = .048), radical resection (compared with local/partial resection; P = .040), high histological grade (P = .037), and LNM (P < .001) were each associated with poor prognosis. By multivariate analysis, chronological age (P = .011) and LNM (P = .002) were independent prognostic factors. High histological grade (P = .003) was an independent predictive factor for LNM. In our series, chronological age and LNM were independent prognostic factors for CSS. The histological grade, not the tumor stage, was still an influential predictive factor of LNM in Chinese patients with penile SCC.
Dr Claude Gagnon.
O'Flaherty C, de Lamirande E, Leclerc P … +2 more , Lefievre L, Robaire B
J Androl · 2012 · PMID 22700765 · Publisher ↗
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Cryopreservation of human spermatozoa decreases the number of motile normal spermatozoa, induces nuclear vacuolization and chromatin decondensation.
Boitrelle F, Albert M, Theillac C … +6 more , Ferfouri F, Bergere M, Vialard F, Wainer R, Bailly M, Selva J
J Androl · 2012 · PMID 22700764 · Publisher ↗
Even though cryopreservation of human spermatozoa is known to alter sperm motility and viability, it may also induce nuclear damages. The present study set out to determine whether or not cryopreservation alters motile s...
Even though cryopreservation of human spermatozoa is known to alter sperm motility and viability, it may also induce nuclear damages. The present study set out to determine whether or not cryopreservation alters motile sperm morphology under high magnification and/or is associated with chromatin decondensation. For 25 infertile men, we used high-magnification microscopy to determine the proportions of various types of motile spermatozoa before and after freezing-thawing: morphometrically normal spermatozoa with no vacuole (grade I), ≤ 2 small vacuoles (grade II), at least 1 large vacuole or >2 small vacuoles (grade III), and morphometrically abnormal spermatozoa (grade IV). The spermatozoa's chromatin condensation and viability were also assessed before and after freezing-thawing. Cryopreservation induced sperm nuclear vacuolization. It decreased the proportion of grade I + II spermatozoa (P < .001). It induced a decrease in the sperm viability rate (P < .001) and increased the proportion of sperm with noncondensed chromatin (P < .001). The latter parameter was strongly correlated with sperm viability (r = 0.71; P < .001). However, even motile sperm presented a failure of chromatin condensation after freezing-thawing, because the proportion of sperm with noncondensed chromatin was correlated with high-magnification morphology (r = -0.49 and 0.49 for the proportions of grade I + II and grades III + IV, respectively; P < .001). Cryopreservation alters the organelle morphology of motile human spermatozoa and induces sperm chromatin decondensation. High-magnification microscopy may be useful for evaluating frozen-thawed spermatozoa before use in assisted reproductive technology procedures (such as intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection) and for performing research on cryopreservation methods. If frozen-thawed sperm is to be used for intracytoplasmic sperm injection, morphological selection under high magnification may be of particular value.
Priapism as the initial manifestation of a penile and lower limb cutaneous metastasis of prostate adenocarcinoma with low serum PSA level.
He D, Zeng J, Li X … +5 more , Wu K, Wu D, He H, Song W, Li L
J Androl · 2012 · PMID 22700763 · Publisher ↗
Penile and/or cutaneous metastases from prostate adenocarcinoma rarely occur. Here, we detail the case of a 78-year-old man suffering from priapism caused by metastatic prostate cancer with both penile and lower limb cut...
Penile and/or cutaneous metastases from prostate adenocarcinoma rarely occur. Here, we detail the case of a 78-year-old man suffering from priapism caused by metastatic prostate cancer with both penile and lower limb cutaneous spread. His serum prostate-specific antigen level was 0.09 μg/L when priapism developed. Corpora cavernosa biopsy was refused by the patient and radical penectomy was performed. Postoperative pathologic and immunohistochemical studies revealed undifferentiated prostate adenocarcinoma cells growing in corpora cavernosa. Two months later, the patient presented with multiple, erythematous nodules over the right lower leg. The prostate-specific antigen level was found to be 0.264 μg/L. Biopsy of a skin nodule revealed neoplastic cells consistent with metastatic prostate adenocarcinoma. This is the first known case of metastatic prostate cancer found in both penis and skin with a low serum prostate-specific antigen level. Priapism presented as the initial clinical manifestation of metastatic prostate cancer.
Antiandrogenic activity of resveratrol analogs in prostate cancer LNCaP cells.
Iguchi K, Toyama T, Ito T … +5 more , Shakui T, Usui S, Oyama M, Iinuma M, Hirano K
J Androl · 2012 · PMID 22700762 · Publisher ↗
The suppression of androgen signaling is a therapeutic target for the treatment of prostate cancer. Resveratrol (3,4',5-trihydroxystilbene) is known to inhibit the function of the androgen receptor (AR). In the present s...
The suppression of androgen signaling is a therapeutic target for the treatment of prostate cancer. Resveratrol (3,4',5-trihydroxystilbene) is known to inhibit the function of the androgen receptor (AR). In the present study, we investigated the antiandrogenic activities of resveratrol analogs in order to identify a potent antiandrogen compound. Resveratrol analogs were isolated from plants or were semisynthesized from resveratrol. AR transcriptional activity was measured in prostate cancer LNCaP cells using a luciferase assay with the MMTV-luc reporter plasmid. Among the resveratrol analogs tested, 4'-O-methylresveratrol (3,5-dihydroxy-4'-methoxystilbene) was the most effective inhibitor of AR transcriptional activity. Introduction of a methoxy group to the C-4' of resveratrol and its analogs increased their antiandrogenic activity compared with the unmodified counterparts. Conversely, modification of the 3- and/or 5-hydroxyl groups reduced the antiandrogenic activity. 4'-O-methylresveratrol was more effective than resveratrol in inhibiting Akt phosphorylation, which is related to AR signaling, in LNCaP cells. The hydroxyl groups in resveratrol play a key role in their antiandrogenic effect by modulating AR transcriptional activity.
Highly active antiretroviral therapy (HAART) and testicular morphology: current status and a case for a stereologic approach.
Azu OO
J Androl · 2012 · PMID 22700761 · Publisher ↗
As antiretroviral therapy becomes increasingly accessible, the associated improvements in the health, quality of life, and survival of patients are anticipated to influence the fertility determinants of patients, specifi...
As antiretroviral therapy becomes increasingly accessible, the associated improvements in the health, quality of life, and survival of patients are anticipated to influence the fertility determinants of patients, specifically young males, within the reproductive axis. Therefore, the understanding of testicular histology in patients with HIV/AIDS undergoing therapeutic management is essential, because the sexual route is one of the main means of transmission of HIV, which is localized primarily in the germ cells of the testes. It is also important to determine whether any changes have occurred in the testicular histologic patterns in the course of the HIV/AIDS therapy. This review highlights the views of experts that current therapy and prolongation of survival in HIV/AIDS patients are associated with a shift in the histologic findings of testes toward a more pronounced loss of germ cells. There have been attempts to use stereologic size and number estimators to quantify the volume or number of biologically significant reference spaces and objects from their appearance on two-dimensional sections without introducing bias from inappropriate assumptions, models, or correction formulas. Therefore, morphologic changes related to altered distribution of highly active retroviral therapy within the testis and the consequent endocrine perturbations characteristic of a potential complication of antiretroviral treatment regimens can be analyzed in stereologic dimensions.
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