New approaches concerning the testis of Astyanax lacustris (Characidae): immunohistochemical studies.

Astyanax lacustris, locally known as lambari-do-rabo-amarelo, is a study model for Neotropical fish. Testis of A. lacustris shows deep morphophysiological changes throughout the annual reproductive cycle. This work analyzed the distribution of claudin-1, actin, and cytokeratin as elements of the cytoskeleton in germinal epithelium and interstitium; the distribution of type I collagen, fibronectin, and laminin as extracellular matrix compounds; and the localization of androgen receptor in the testis of this species. Claudin-1, cytokeratin, and actin were present in the Sertoli cells and modified Sertoli cells, and actin was also detected in peritubular myoid cells. Type I collagen were in the interstitial tissue, laminin in the basement membrane of germinal epithelium and endothelium, but fibronectin was additionally detected in the germinal epithelium compartment. The labeling of androgen receptor was higher in peritubular myoid cells and undifferentiated spermatogonia, and weaker labeling was detected in type B spermatogonia. Therefore, the present work highlights new aspects of the biology of the testis of A. lacustris, and contribute to amplify the understanding of this organ.

The role of testosterone in the respiratory and thermal responses to hypoxia and hypercapnia in rats.

Many diseases of the respiratory system occur differently in males and females, indicating a possible role of gonadal hormones in respiratory control. We hypothesized that testosterone (T) is important for the ventilatory chemosensitivity responses in males. To test this hypothesis, we evaluated ventilation (V̇ E), metabolic rate and body temperature (Tb) under normoxia/normocapnia, hypercapnia and hypoxia in orchiectomized (ORX), ORX with testosterone replacement (ORX + T) or flutamide (FL, androgen receptor blocker)-treated rats. We also performed immunohistochemistry to evaluate the presence of androgen receptor (AR) in the carotid body (CB) of intact males. Orchiectomy promoted a reduction V̇ E and ventilatory equivalent (V̇ E /V̇ O2) under room-air conditions, which was restored with testosterone treatment. Moreover, during hypoxia or hypercapnia, animals that received testosterone replacement had a higher V̇ E and V̇ E /V̇ O2 than control and ORX, without changes in metabolic and thermal variables. Flutamide decreased the hypoxic ventilatory response without changing the CO2-drive to breathe, suggesting that the testosterone effect on hypercapnic hyperventilation does not appear to involve the AR. We also determined the presence of AR in the CB of intact animals. Our findings demonstrate that testosterone seems to be important for maintaining resting V̇ E in males. In addition, the influence of testosterone on V̇ E, either during resting conditions or under hypoxia and hypercapnia, seems to be a direct and specific effect, as no changes in metabolic rate or Tb were observed during any treatment. Finally, a putative site of testosterone action during hypoxia is the CB, since we detected the presence of AR in this structure.

Hypothalamic transcriptional expression of the kisspeptin system and sex steroid receptors differs among polycystic ovary syndrome rat models with different endocrine phenotypes.

OBJECTIVES:: Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects reproductive-age women. The mechanisms underlying the endocrine heterogeneity and neuroendocrinology of polycystic ovary syndrome are still unclear. In this study, we investigated the expression of the kisspeptin system and gonadotropin-releasing hormone pulse regulators in the hypothalamus as well as factors related to luteinizing hormone secretion in the pituitary of polycystic ovary syndrome rat models induced by testosterone or estradiol. METHODS:: A single injection of testosterone propionate (1.25 mg) (n=10) or estradiol benzoate (0.5 mg) (n=10) was administered to female rats at 2 days of age to induce experimental polycystic ovary syndrome. Controls were injected with a vehicle (n=10). Animals were euthanized at 90-94 days of age, and the hypothalamus and pituitary gland were used for gene expression analysis. RESULTS:: Rats exposed to testosterone exhibited increased transcriptional expression of the androgen receptor and estrogen receptor-ß and reduced expression of kisspeptin in the hypothalamus. However, rats exposed to estradiol did not show any significant changes in hormone levels relative to controls but exhibited hypothalamic downregulation of kisspeptin, tachykinin 3 and estrogen receptor-α genes and upregulation of the gene that encodes the kisspeptin receptor. CONCLUSIONS:: Testosterone- and estradiol-exposed rats with different endocrine phenotypes showed differential transcriptional expression of members of the kisspeptin system and sex steroid receptors in the hypothalamus. These differences might account for the different endocrine phenotypes found in testosterone- and estradiol-induced polycystic ovary syndrome rats.

Hypothalamic transcriptional expression of the kisspeptin system and sex steroid receptors differs among polycystic ovary syndrome rat models with different endocrine phenotypes

OBJECTIVES: Polycystic ovary syndrome is a heterogeneous endocrine disorder that affects reproductive-age women. The mechanisms underlying the endocrine heterogeneity and neuroendocrinology of polycystic ovary syndrome are still unclear. In this study, we investigated the expression of the kisspeptin system and gonadotropin-releasing hormone pulse regulators in the hypothalamus as well as factors related to luteinizing hormone secretion in the pituitary of polycystic ovary syndrome rat models induced by testosterone or estradiol. METHODS: A single injection of testosterone propionate (1.25 mg) (n=10) or estradiol benzoate (0.5 mg) (n=10) was administered to female rats at 2 days of age to induce experimental polycystic ovary syndrome. Controls were injected with a vehicle (n=10). Animals were euthanized at 90-94 days of age, and the hypothalamus and pituitary gland were used for gene expression analysis. RESULTS: Rats exposed to testosterone exhibited increased transcriptional expression of the androgen receptor and estrogen receptor-β and reduced expression of kisspeptin in the hypothalamus. However, rats exposed to estradiol did not show any significant changes in hormone levels relative to controls but exhibited hypothalamic downregulation of kisspeptin, tachykinin 3 and estrogen receptor-α genes and upregulation of the gene that encodes the kisspeptin receptor. CONCLUSIONS: Testosterone- and estradiol-exposed rats with different endocrine phenotypes showed differential transcriptional expression of members of the kisspeptin system and sex steroid receptors in the hypothalamus. These differences might account for the different endocrine phenotypes found in testosterone- and estradiol-induced polycystic ovary syndrome rats.

Musk gland seasonal development and musk secretion are regulated by the testis in muskrat (Ondatra zibethicus).

BACKGROUND: The muskrat is a seasonal breeder. Males secrete musk to attract females during the breeding season. The testosterone binding to the androgen receptor (AR) in musk glands of muskrat may play an important role conducting the musk secretion process. METHODS: The musk gland, testis and blood samples of musk rats are collected in both breeding and non-breeding seasons. Some part of the samples are kept in liquid nitrogen for transcriptome analysis and Western blotting test. Some part of the samples are kept in 70% alcohol for histology experiment, blood samples are kept at -20 °C for the serum testosterone measurement experiment. RESULTS: This study demonstrates that the quantity of secreted musk, the volume of the musk glands, the diameter of the gland cells and AR expression are all higher during the breeding season than at other times (p < 0.01). StAR, P450scc and 3ß-HSD expression in the Leydig cells of the testis were also higher during this season, as was serum testosterone. AR was also observed in the gland cells of two other musk-secreting animals, the musk deer and small Indian civet, in their musk glands. These results suggest that the testes and musk glands co-develop seasonally. CONCLUSION: The musk glands' seasonal development and musk secretion are regulated by the testes, and testosterone plays an important role in the seasonal development of musk glands.

Role of resistance physical exercise in preventing testicular damage caused by chronic ethanol consumption in UChB rats.

Ethanol consumption is associated with spermatogenesis damage and testosterone level alterations. Alcohol remains the most commonly used substance among athletes and sports enthusiasts. This study evaluated whether resistance physical exercise can reduce the testicular damage caused by ethanol exposure. A total of 36 ethanol drinking (UChB) rats were divided into four groups: C (control rats), ETOH (ethanol consumption), ETOH + T (ethanol consumption + physical training), and T (group physical training). The physical training component of the T and ETOH + T groups was based on a resistance training model consisting of four sets of 10 jumps, with an increasing overload of 50-70% of the body weight attached to the chest three times per week. Rats in the ETOH and ETOH +T groups received 10% ethanol. At postnatal day 90, the rats were sacrificed. Blood sample was collected for hormonal analysis, and the testicles were weighed and processed for histopathological, morphometric, and immunohistochemical analyses. The ETOH group showed an increase in testosterone levels. The immunohistochemical of androgen receptor and the absolute weight of the testes were higher in the ETOH and ETOH + T groups, while the ETOH animals showed a decreased weight gain index. The number of abnormal seminiferous tubules increased in the ETOH and T groups compared to those in the control group (C); however, the association with treatment (ETOH + T group) prevented this effect and decreased caspase-3 production. In conclusion, these findings show that the combination of ethanol consumption and resistance physical exercise can prevent testicular damage in adult UChB rats.

Lymphocyte-predominant triple-negative breast carcinomas in premenopausal patients: Lower expression of basal immunohistochemical markers.

OBJECTIVES: Triple-negative breast carcinomas (TNBCs) correspond to a molecular heterogeneous disease defined by lack of estrogen and progesterone receptor expression, and the absence of overexpression and/or amplification of HER2. Recent data indicate that clinical outcome in TNBC is affected by tumor-infiltrating lymphocytes, suggesting that they can benefit from immunotherapies. We selected 116 consecutive premenopausal patients with TNBC to compare the immunohistochemical profile of the group rich in tumor-infiltrating lymphocytes with those without this characteristic. MATERIALS AND METHODS: We reviewed all the original histological sections to assess pathological features, and to select a representative area for tissue microarrays and immunohistochemical study. Estrogen and progesterone receptors, HER2 and Ki-67 were evaluated in whole histological sections. The following markers were analyzed in tissue microarrays sections: androgen receptor, cytokeratin 5/6, cytokeratin 14, epidermal growth factor receptor (EGFR), vimentin, p16, claudin-3, -4, and -7, p63, and aldehyde dehydrogenase isoform 1 (ALDH1). Lymphocyte-predominant breast cancer (LPBC) was defined by the presence of more than 50% of lymphocytes in the intratumoral stroma. RESULTS: Twenty-six (22.4%) patients present tumors classified as LPBC and 90 (77.6%) as non-LPBC. The two groups were similar regarding age of patients, tumor grade and Ki-67 positive cells. LPBC cases presented lower frequency of expression of the basal cytokeratins, EGFR, and basal-like immunoprofile. There was a trend to higher expression of ALDH1 by stromal intratumoral cells. The expression of all other markers were similar in the two groups. CONCLUSIONS: Lymphocyte-predominant TNBC in premenopausal patients are mostly of non-basal phenotype.

Musk gland seasonal development and musk secretion are regulated by the testis in muskrat (Ondatra zibethicus)

BACKGROUND: The muskrat is a seasonal breeder. Males secrete musk to attract females during the breeding season. The testosterone binding to the androgen receptor (AR) in musk glands of muskrat may play an important role conducting the musk secretion process. METHODS: The musk gland, testis and blood samples of musk rats are collected in both breeding and non-breeding seasons. Some part of the samples are kept in liquid nitrogen for transcriptome analysis and Western blotting test. Some part of the samples are kept in 70% alcohol for histology experiment, blood samples are kept at -20 °C for the serum testosterone measurement experiment. RESULTS: This study demonstrates that the quantity of secreted musk, the volume of the musk glands, the diameter of the gland cells and AR expression are all higher during the breeding season than at other times (p < 0.01). StAR, P450scc and 3ß-HSD expression in the Leydig cells of the testis were also higher during this season, as was serum testosterone. AR was also observed in the gland cells of two other musk-secreting animals, the musk deer and small Indian civet, in their musk glands. These results suggest that the testes and musk glands co-develop seasonally. CONCLUSION: The musk glands' seasonal development and musk secretion are regulated by the testes, and testosterone plays an important role in the seasonal development of musk glands.

Role of the TNF-α receptor type 1 on prostate carcinogenesis in knockout mice.

BACKGROUND: TNF-α is a key cytokine involved in prostate carcinogenesis and is mediated by the TNF-α receptor type 1 (TNFR-1). This receptor triggers two opposite pathways: cell death or cell survival and presents a protective or stimulator role in cancer. Thus, the purpose of this study was to evaluate the role of TNF signaling in chemically induced prostate carcinogenesis in mice. METHODS: C57bl/6 wild type (WT) and p55 TNFR-1 knockout mice (KO) were treated with mineral oil (control) or N-methyl N-nitrosurea (MNU) in association with testosterone (MNU+T, single injection of 40 mg/kg and weekly injection 2 mg/kg, respectively) over the course of 6 months. After this induction period, prostate samples were processed for histological and biochemical analysis. RESULTS: MNU+T treatment led to the development of prostate intraepithelial neoplasia (PIN) and adenocarcinoma (PCa) in both WT and KO animals; however, the incidence of PCa was lower in KO group than in WT. Cell proliferation analysis showed that PCNA levels were significantly lower in the KO group, even after carcinogenesis induction. Furthermore, the prostate of KO animals had lower levels of p65 and p-mTOR after treatment with MNU+T than WT. There was also a decrease in prostate androgen receptor levels after induction of carcinogenesis in both KO and WT mice. Regarding the extracellular matrix in the prostate, KO mice had higher levels of fibronectin and lower levels of matrix metalloproteinase 2 (MMP2) after carcinogenesis. Finally, there was a similar increase in apoptosis in both groups after carcinogenesis, indicating that the TNAFr1 pathway in prostate carcinogenesis presented proliferative, and not apoptotic, stimuli. CONCLUSIONS: TNF-α, through its receptor TNFR-1, promoted cell proliferation and cell survival in prostate by activation of the AKT/mTOR and NFKB pathway, which stimulated prostate carcinogenesis in chemically induced mice. Prostate 76: 917-926, 2016. © 2016 Wiley Periodicals, Inc.

Gestational protein restriction delays prostate morphogenesis in male rats.

Maternal malnutrition due to a low-protein diet is associated with functional disorders in adulthood, which may be related to embryonic development failures. The effects of gestational protein restriction on prostate morphogenesis in male offspring were investigated. Pregnant rat dams were divided into normoprotein (NP; fed a normal diet containing 17% protein) and hypoprotein (LP; fed a diet containing 6% protein) groups. On the day of birth (PND1), anogenital distance and bodyweight were measured in male pups. Seven males per experimental group (one male per litter) were killed, and the pelvic urethra was evaluated. LP offspring showed a significant reduction in bodyweight and anogenital distance on PND1. On three-dimensional reconstruction of the prostate, the number of prostatic buds was lower in LP than in NP males. Mesenchymal cells surrounding the buds were androgen-receptor positive, and the quantity and intensity of nucleus immunoreactivity was decreased in LP. The proliferation index was lower in LP than in NP prostatic buds. Immunoreactivity for α-actin in mesenchymal cells and that for epidermal growth factor receptor in epithelial cells was higher in NP than in LP. Our findings demonstrate that maternal protein restriction delays prostatic morphogenesis, probably because of considerable disruption in the epithelium-mesenchyme interaction.

Prostatic microenvironment in senescence: fibroblastic growth factors × hormonal imbalance.

The aim was to characterize and correlate steroid hormone receptors with the FGF2, FGF7 and FGF8 reactivities in the prostatic epithelium and stroma in senile rats. Fifty male senile rats and 10 young male rats were divided into the young (YNG), the senile groups (SE), the castrated group (CAS), the estrogen-deficient group (ED), the castrated + estrogen group (CASE), and the estrogen-deficient + androgen group (EDTEST). The ventral prostate was submitted to immunohistochemical and Western blotting analyses. The results showed decreased AR and ERß levels and increased ERα in the senile animals in relation to YNG group. Increased ERα and ERß reactivities presenting differential localization were characterized in the CASE group compared to the CAS group. Increased FGF2 level was observed in the stroma of the CAS and ED groups in relation to the SE group and in the epithelium of the ED group in relation to the other groups. Increased and differential immunolocalization of FGF7 levels were observed in the CAS, ED and CASE groups. The FGF8 levels showed differential localization in the CAS and ED groups compared to the senile group. The intense hormone ablation was favorable to the autocrine signaling of FGF2 and FGF8. FGF7 could be activated in the androgen-independent via considering the increased FGF7 in the castrated rats. We concluded that hormone ablation in senescence was favorable to activation or/and to fibroblast signaling in the prostatic microenvironment.

Effects of castration on androgen receptors and gonadotropins in the pituitary of adult male viscachas.

The aims of the present study were to determine whether castration results in quantitative immunohistochemical changes in androgen receptors (AR), LH-immunoreactive (IR) cells and FSH-IR cells, and to analyse the colocalisation of AR and gonadotropins in the pituitary pars distalis (PD) of viscachas. Pituitaries were processed for light and electron microscopy. AR-IR, LH-IR and FSH-IR cells were detected by immunohistochemistry. In morphometric studies, the percentage of AR-IR, LH-IR, FSH-IR, LH-IR/AR-IR and FSH-IR/AR-IR cells was determined. In intact viscachas, AR were distributed throughout the PD; they were numerous at the caudal end, with intense immunostaining. LH-IR cells and FSH-IR cells were found mainly in the ventral region and at the rostral end of the PD. Approximately 45%-66% of LH-IR cells and 49%-57% of FSH-IR cells expressed AR in the different zones of the PD. In castrated viscachas, there was a significant decrease in the percentage of AR-IR, LH-IR, FSH-IR, and FSH-IR/AR-IR cells. Some pituitary cells from castrated viscachas also exhibited ultrastructural changes. These results provide morphological evidence that gonadal androgens are directly related to the immunolabelling of AR, LH and FSH. Moreover, the colocalisation of AR and FSH is most affected by castration, suggesting the existence of a subpopulation of gonadotrophs with different regulatory mechanisms for hormonal synthesis, storage and secretion.

Implications of intrauterine protein malnutrition on prostate growth, maturation and aging.

AIMS: Maternal malnutrition by low protein diet is associated with an increased incidence of metabolic disorders and decreased male fertility in adult life. This study aimed to assess the impact of maternal protein malnutrition (MPM) on prostate growth, tissue organization and lesion incidence with aging. MAIN METHODS: Wistar rat dams were distributed into two groups, which were control (NP; fed a normal diet containing 17% protein) or a restricted protein diet (RP, fed a diet containing 6% protein) during gestation. After delivery all mothers and offspring received a normal diet. Biometrical parameters, hormonal levels and prostates were harvested at post-natal days (PND) 30, 120 and 360. KEY FINDINGS: MPM promoted low birth weight, decreased ano-genital distance (AGD) and reduced androgen plasma levels of male pups. Prostatic lobes from RP groups presented reduced glandular weight, epithelial cell height and alveolar diameter. The epithelial cell proliferation and collagen deposition were increased in RP group. Incidences of epithelial dysplasia and prostatitis were higher in the RP offspring than in the NP offspring at PND360. SIGNIFICANCE: Our findings show that MPM delays prostate development, growth and maturation until adulthood, probably as a result of low testosterone stimuli. The higher incidence of cellular dysplasia and prostatitis suggests that MPM increases prostate susceptibility to diseases with aging.

Coordinated expression of oestrogen and androgen receptors in HER2-positive breast carcinomas: impact on proliferative activity.

AIMS: Human epidermal growth factor receptor 2 (HER2)-positive breast cancers are aggressive neoplasms associated with a variable response to systemic therapies. Therefore, the identification of biomarkers to better characterise this heterogeneity would improve treatment efficacy. The aim of this study was to evaluate the influence of androgen receptor (AR) and oestrogen receptor (ER) on clinicopathological features in a series of HER2-positive breast carcinomas. METHODS: A total of 104 carcinomas were selected and reviewed. Immunohistochemical studies for ER, progesterone receptor and Ki-67 were analysed on tumour whole histological sections. AR expression was analysed on samples represented on tissue microarrays. According to steroid receptor expression, cases were classified into three groups: AR positive/ER positive (48 cases), AR positive/ER negative (41 cases) and AR negative/ER negative (13 cases). RESULTS: AR-positive tumours corresponded to 89 (85.6%) of 104 carcinomas. AR-positive carcinomas were associated with a higher frequency of ER and progesterone receptor co-expression and lower proliferative activity determined by the expression of Ki-67. AR-negative carcinomas were more often high grade. The group of AR-positive/ER-negative carcinomas was associated with the highest frequency of apocrine morphological features. The group of AR-negative/ER-negative carcinomas was associated with the highest proliferative activity and the highest frequency of high histological and nuclear grade. The lowest frequency of high-grade tumours and the lowest proliferative activity were seen among tumours with expression of both receptors. CONCLUSIONS: These results suggest that co-expression of AR and ER can provide a protective effect based on phenotypical presentation of HER2-positive carcinomas. Furthermore, lack of both steroid hormone receptors characterises the most aggressive phenotype.

The effect of microgravity on tissue structure and function of rat testis

To explore whether an environment of weightlessness will cause damage to the reproductive system of animals, we used the tail-suspension model to simulate microgravity, and investigated the effect of microgravity on the tissue structure and function of the testis in sexually mature male rats. Forty-eight male Wistar rats weighing 200-250 g were randomly assigned to three groups (N = 16 each): control, tail traction, and tail suspension. After the rats were suspended for 7 or 14 days, morphological changes of testis were evaluated by histological and electron microscopic methods. The expression of HSP70, bax/bcl-2 and AR (androgen receptor) in testis was measured by immunohistochemistry. Obvious pathological lesions were present in the testis after the rats were suspended for 7 or 14 days. We detected overexpression of HSP70 and an increase of apoptotic cells, which may have contributed to the injury to the testis. The expression of AR, as an effector molecule in the testis, was significantly decreased in the suspended groups compared to control (P < 0.01). We also observed that, with a longer time of suspension, the aforementioned pathological damage became more serious and some pathological injury to the testis was irreversible. The results demonstrated that a short- or medium-term microgravity environment could lead to severe irreversible damage to the structure of rat testis.

The effect of microgravity on tissue structure and function of rat testis.

To explore whether an environment of weightlessness will cause damage to the reproductive system of animals, we used the tail-suspension model to simulate microgravity, and investigated the effect of microgravity on the tissue structure and function of the testis in sexually mature male rats. Forty-eight male Wistar rats weighing 200-250 g were randomly assigned to three groups (N = 16 each): control, tail traction, and tail suspension. After the rats were suspended for 7 or 14 days, morphological changes of testis were evaluated by histological and electron microscopic methods. The expression of HSP70, bax/bcl-2 and AR (androgen receptor) in testis was measured by immunohistochemistry. Obvious pathological lesions were present in the testis after the rats were suspended for 7 or 14 days. We detected overexpression of HSP70 and an increase of apoptotic cells, which may have contributed to the injury to the testis. The expression of AR, as an effector molecule in the testis, was significantly decreased in the suspended groups compared to control (P < 0.01). We also observed that, with a longer time of suspension, the aforementioned pathological damage became more serious and some pathological injury to the testis was irreversible. The results demonstrated that a short- or medium-term microgravity environment could lead to severe irreversible damage to the structure of rat testis.

Absolute measurement of androgen receptor mRNA in peripheral blood mononuclear, preputial skin and urethral mucosa cells of control individuals with phimosis using qRT-PCR / Valor absoluto do mRNA do receptor androgênico em células mononucleares do sangue periférico e células da pele do prepúcio e mucosa uretral em indivíduos controle com fimose, determinado por meio de qRT-PCR

INTRODUCTION: Androgen actions are exerted upon the androgen receptor (AR), and complete genital virilization of normal 46,XY individuals depends on adequate function and expression of the AR gene in a tissue-specific manner. OBJECTIVE: Standardization of normal ARmRNA in androgen-sensitive tissues. MATERIALS AND METHODS: In this study, we determined the quantitative amounts of ARmRNA in peripheral blood mononuclear, urethral mucosa and preputial skin cells of control subjects with phimosis by using RT-PCR. RESULTS: The mean (SD) values of AR expression in blood, urethra and prepuce were: 0.01 (0.01); 0.43 (0.32); 0.31 (0.36), respectively. CONCLUSION: The AR expression is low in blood and equivalent in urethral mucosa and preputial skin, which may be useful in the diagnosis of individuals with abnormal external genitalia.

INTRODUÇÃO: As ações androgênicas são exercidas por meio do receptor androgênico (AR), e a completa virilização genital de indivíduos 46,XY normais depende de adequada expressão do gene AR de forma tecido específica. OBJETIVO: Padronizar valores normais de ARmRNA em tecidos sensíveis aos andrógenos. MATERIAIS E MÉTODOS: Neste estudo, determinamos as quantidades de ARmRNA em células mononucleares do sangue periférico e em células da mucosa uretral e pele do prepúcio de indivíduos controles com fimose, utilizando RT-PCR. RESULTADOS: A média (dp) dos valores de expressão do AR em sangue, uretra e prepúcio foram: 0,01 (0,01); 0,43 (0,32); 0,31 (0,36), respectivamente. CONCLUSÃO: A expressão do AR é baixa em sangue periférico e equivalente em mucosa uretral e pele prepucial, sendo sua quantificação útil no diagnóstico de indivíduos com alterações da genitália externa.

Stem cells and androgen receptor in human periapical periodontitis / Células madre y receptor de andrógenos en periodontitis periapical humana

Activation of macrophages in periapical granulomas occurs through the presence of cytokines, endotoxin and other genetic and epigenetic factors, allowing the initiation of inflammation and bone resorption. The present study aims to analyze the presence of CD133 protein (marker of stem cells) and the AR (androgen receptor) protein in biopsies of human odontogenic periapical granuloma. Biopsies from 14 adult male patients with diagnosis of periapical granuloma included in paraffin blocks were processed histologically to obtain 5-um thick sections. Protein presence was detected and analyzed by immunohistochemistry of CD133 and AR. The quantification considered the number of positive cells in 0.17 mm2 random areas under the microscope using a 1000X objective. Both CD133 and AR proteins are expressed abundantly in cells in pathological periapical granulomas tissue. The number of cells expressing CD133 and AR shows a wide variation coefficient, so its variation is a particular feature for each individual. We concluded that in human odontogenic periapical granuloma there are abundant stem cells and cells expressing AR that may be important for the pathogenic inflammatory process.

La activación de los macrófagos en los granulomas periapicales humanos se producen a través de la presencia de citoquinas, endotoxinas y otros factores genéticos y epigenéticos que permiten la iniciación de la inflamación y la reabsorción ósea. El presente estudio pretende analizar la presencia de proteína CD133 (marcador de células madre) y de la proteína RA (receptor de andrógenos) en las biopsias de granulomas periapicales odontogénicos humanos. Las biopsias de 14 pacientes varones adultos con diagnóstico de granuloma periapical fueron incluidos en bloques de parafina y se procesaron histológicamente para obtener secciones de 5 micras de espesor. La presencia de CD133 y RA fueron detectadas y analizadas por inmunohistoquímica. La cuantificación se realizó considerando el número de células positivas en áreas al azar de 0,17mm2, utilizando microscopio con objetivo de 1000X. Ambas proteínas, CD133 y RA se expresan en abundancia en las células del tejido patológico con granuloma periapical. El número de células que expresan CD133 y RA presentan un amplio coeficiente de variación, por lo que su variación es una característica particular de cada individuo. Se concluye que en granuloma periapical odontogénico humano se expresan abundantes células madre y proteínas receptoras de andrógenos, antecedentes que pueden sermuy importantes en la expresión y diagnosis de los procesos patológicos inflamatorios.

Parallel determination of NeuroD1, chromogranin-A, KI67 and androgen receptor expression in surgically treated prostate cancers.

PURPOSE: Neuroendocrine differentiation is a hallmark of prostate cancer. The aim of our study was the detection of the parallel expression of neuroendocrine related markers using a prostate tissue microarray (TMA). MATERIALS AND METHODS: Our study was aimed at detecting the parallel expression of NeuroD1, Chromogranin-A (ChrA), Androgen Receptor (AR) and Ki-67 by immunohistochemistry on prostate cancer tissue microarray. The data was analyzed using SAS version 8.2 (SAS Inc, Cary, NC). The relationships between NeuroD1, ChrA and AR expressions and patients' characteristics were investigated by multivariate logistic regression analysis. Progression and Overall Survival (OS) distributions were calculated using Kaplan-Meier method. RESULTS: Tissue reactivity for NeuroD1, ChrA and AR concerned 73%, 49% and 77% of the available cases, respectively. Regarding overall survival, there were 87 deaths and 295 patients alive/censored (6 years of median follow-up). Seventy-seven disease progressions occurred at the median follow-up 5.4y. A significant correlation between NeuroD1, ChrA and AR expression was observed (p < 0.001 and p < 0.03, respectively). Additionally, ChrA was strongly associated in multivariate analysis to Gleason score and Ki67 expression (p < 0.009 and p < 0.0052, respectively). Survival analysis showed no association between markers neither for overall nor for cancer-specific survival. CONCLUSIONS: The results highlight that NeuroD1, Chromogranin-A and Androgen Receptor are strongly associated, however their expression does not correlate with overall survival or disease progression.