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1.
Zygote ; 31(4): 386-392, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37212054

RESUMO

Estradiol and progesterone have been recognized as important mediators of reproductive events in the female mainly via binding to their receptors. This study aimed to characterize the immunolocalization of the estrogen receptor alfa (ERα), estrogen receptor beta (ERß) and progesterone receptor (PR) in the ovarian follicles of the lizard Sceloporus torquatus. The localization of steroid receptors has a spatio-temporal pattern that depends on the stage of follicular development. The immunostaining intensity of the three receptors was high in the pyriform cells and the cortex of the oocyte of previtellogenic follicles. During the vitellogenic phase, the granulosa and theca immunostaining was intense even with the modification of the follicular layer. In the preovulatory follicles, the receptors were found in yolk and additionally, ERα was also located in the theca. These observations suggest a role for sex steroids in regulating follicular development in lizards, like other vertebrates.


Assuntos
Receptor alfa de Estrogênio , Lagartos , Animais , Feminino , Receptor alfa de Estrogênio/análise , Receptor alfa de Estrogênio/metabolismo , Lagartos/metabolismo , Folículo Ovariano/metabolismo , Oócitos/metabolismo , Receptor beta de Estrogênio/análise , Receptor beta de Estrogênio/metabolismo , Estradiol/farmacologia , Estradiol/metabolismo , Células da Granulosa/metabolismo
2.
Histochem Cell Biol ; 157(3): 359-369, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35024954

RESUMO

High-mobility group box 2 (HMGB2) is a chromatin-associated protein that is an important regulator of gene transcription, recombination, and repair processes. The functional importance of HMGB2 has been reported in various organs, including the testis, heart, and cartilage. However, its role in the ovary is largely unknown. In this study, ovary tissues from wild-type (WT) and HMGB2-knock-out (KO) mice were examined by histopathological staining and immunohistochemistry. The ovary size and weight were significantly lower in HMGB2-KO mice than in age-matched WT littermates. Histopathological analysis revealed ovarian atrophy and progressive fibrosis in 10-month-old HMGB2-KO mouse ovaries. Compared to age-matched WT mice, the numbers of oocytes and developing follicles were significantly decreased at 2 months of age and were completely depleted at 10 months of age in HMGB2-KO mice. Immunohistochemistry revealed the expression of HMGB2 in the granulosa cells of developing follicles, oocytes, some corpora lutea, and stromal cells. Importantly, HMGB2-positive cells were co-localized with estrogen receptor beta (ERß), but not ERα. Estrogen response element-binding activity was demonstrated by southwestern histochemistry, and it was decreased in HMGB2-KO mouse ovaries. Cell proliferation activity was also decreased in HMGB2-KO mouse ovaries in parallel with the decreased folliculogenesis. These results indicated that the depletion of HMGB2 induced ovarian atrophy that was characterized by a decreased ovarian size and weight, progressive fibrosis, as well as decreased oocytes and folliculogenesis. In conclusion, we demonstrated the crucial role of HMGB2 in mouse ovarian folliculogenesis through ERß expression.


Assuntos
Receptor beta de Estrogênio , Proteína HMGB2 , Animais , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/análise , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Feminino , Células da Granulosa , Proteína HMGB2/análise , Proteína HMGB2/genética , Proteína HMGB2/metabolismo , Camundongos , Camundongos Knockout , Ovário/metabolismo
3.
BMC Nephrol ; 22(1): 324, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34592934

RESUMO

BACKGROUND: Testing for antibodies against podocyte phospholipase A2 receptor-1 (PLA2R) allows clinicians to accurately identify primary membranous nephropathy (MN). Secondary MN is associated with a spectrum of pathology including solid organ malignancy. PLA2R positivity in these patients occurs, although no case of PLA2R-positive MN has been definitively linked to cancer. CASE PRESENTATION: We describe a case of biopsy-proven PLA2R-positive MN, in whom invasive ductal carcinoma of the breast was discovered. The patient underwent surgery and adjuvant chemotherapy (including cyclophosphamide) and went into a sustained complete remission of her nephrotic syndrome. DISCUSSION AND CONCLUSIONS: Case series have reported PLA2R positivity in patients with solid organ malignancy associated MN. Our case is unusual as it is a breast malignancy, and the patients nephrotic syndrome and anti-PLA2Rab titres improved with treatment of the cancer. Here we report, to the best of our knowledge, the first case of oestrogen receptor-2 positive breast cancer associated with PLA2R positive MN in a young lady that was treated successfully by treating the malignancy.


Assuntos
Autoanticorpos/sangue , Neoplasias da Mama/complicações , Glomerulonefrite Membranosa/complicações , Receptores da Fosfolipase A2/imunologia , Adulto , Receptor beta de Estrogênio/análise , Feminino , Glomerulonefrite Membranosa/imunologia , Humanos , Rim/patologia
4.
Int J Exp Pathol ; 99(1): 15-21, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29655286

RESUMO

Oestrogens play an important role in the development and progression of papillary thyroid carcinoma (PTC) through oestrogen receptor (ER)-α and -ß, which may exert different or even opposing actions in PTC. The roles of ERß in ERα-negative PTC are still not clear. This study investigated the expression dynamics of ERß1 (wild-type ERß) and its clinical significance in female ERα-negative PTC patients. ERß1 expression was detected in thyroid tissues of 136 female patients diagnosed with PTC. The relationships between ERß1 expression and clinicopathological/biological factors were also analysed in female ERα-negative PTC patients. The total score for ERß1 was significantly lower in female ERα-negative PTC patients with LNM or ETE when compared to those without LNM or ETE (Z = -2.923, P = 0.003 and Z = -3.441, P = 0.001). Accordingly, the total score for ERß1 was significantly higher in ERα-negative PTC patients expressing E-cadherin compared to patients negative for E-cadherin expression (Z = -2.636, P = 0.008). The total score was lower in ERα-negative PTC patients positive for VEGF expression compared to those negative for VEGF expression (Z = -1.914, P = 0.056). This preliminary study indicates that reduced expression of ERß1 in female ERα-negative PTC patients is associated with greater progression of the disease. This may provide insights into the underlying molecular mechanisms of ERß1 and could help design targeted approaches for treating or even preventing this disease.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Papilar/química , Movimento Celular , Receptor alfa de Estrogênio/análise , Receptor beta de Estrogênio/análise , Neoplasias da Glândula Tireoide/química , Adolescente , Adulto , Idoso , Carcinoma Papilar/secundário , Progressão da Doença , Regulação para Baixo , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Dados Preliminares , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/patologia , Adulto Jovem
5.
Cell Biol Int ; 42(9): 1200-1211, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29771451

RESUMO

Testosterone is often recommended in the treatment of several aging-related conditions. However, there are still questions about the consequences of this therapy in terms of hormonal and inflammatory parameters that are crucial for prostate homeostasis. Thus, we investigate if the testosterone therapy (TT) modulates the hormone receptors and inflammatory cytokines in the ventral prostate of adult rats. Wistar rats aging 150 days were divided into two experimental groups (n = 10/group): T: received subcutaneous injections of testosterone cypionate (5 mg/kg body weight) diluted in corn oil every other day for 4 weeks; and C: received corn oil as vehicle. Animals were euthanized at 180 days old by decapitation. Blood was collected to obtain hormone and cytokines concentrations. The ventral prostate was dissected and processed for light microscope and molecular analyses. Relative ventral prostate weight and epithelial compartment were increased after TT. The number of intact and degranulated mast cells was reduced in the T group. Plasma testosterone, DHT and intraprostatic testosterone concentrations were higher in the T group. TT leads to an increase in cell proliferation and up-regulation of AR, ERß, PAR-4, and NRF2. Importantly, plasma concentration and tissue expression of IL-10 and TNF-α were higher after TT. In summary, these results indicate that TT can regulate inflammatory response, with impacts in cytokines and mast cell population, and modulates steroids receptors, important parameters for prostatic homeostasis.


Assuntos
Próstata/efeitos dos fármacos , Testosterona/análogos & derivados , Animais , Proteínas Reguladoras de Apoptose/análise , Proteínas Reguladoras de Apoptose/sangue , Proliferação de Células/efeitos dos fármacos , Citocinas/análise , Citocinas/sangue , Receptor beta de Estrogênio/análise , Receptor beta de Estrogênio/sangue , Inflamação/metabolismo , Masculino , Fator 2 Relacionado a NF-E2/análise , Fator 2 Relacionado a NF-E2/sangue , Próstata/metabolismo , Ratos , Ratos Wistar , Receptores Androgênicos/metabolismo , Testosterona/metabolismo , Testosterona/farmacologia
6.
Acta Derm Venereol ; 98(9): 867-872, 2018 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-29972220

RESUMO

Becker's naevus is androgen-dependent. The aim of this study was to investigate whether oestrogen and progesterone receptors are involved in this disorder. Immunohistochemistry showed that epidermal expression of androgen receptors, oestrogen receptors (α, ß) and progesterone receptors was higher in skin lesions of Becker's naevus than in perilesional and control skin. Androgen receptor overexpression was observed in pilosebaceous glands, while oestrogen and progesterone receptor overexpression was seen in hair follicles, but not in sebaceous glands in skin lesions compared with perilesional skin. Reverse tran-scription PCR and Western blot revealed that levels of androgen, oestrogen and progesterone receptors were generally upregulated in skin lesions compared with perilesional and control skin, and their expression was usually higher in perilesional than in control skin. These results suggest that simultaneous overexpression of androgen, oestrogen and progesterone receptors might be implicated in the pathogenesis of Becker's naevus.


Assuntos
Receptor alfa de Estrogênio/análise , Receptor beta de Estrogênio/análise , Nevo/química , Receptores Androgênicos/análise , Receptores de Progesterona/análise , Neoplasias Cutâneas/química , Adolescente , Adulto , Western Blotting , Criança , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Nevo/genética , Nevo/patologia , Receptores Androgênicos/genética , Receptores de Progesterona/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Regulação para Cima , Adulto Jovem
7.
Eur J Nutr ; 56(2): 509-519, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26582578

RESUMO

OBJECTIVE: The aim of this study was to determine whether α-linolenic acid (ALA ω-3 fatty acid) enriched diet affects growth parameters when applied to a syngeneic model of mammary carcinoma. MATERIALS AND METHODS: BALB/c mice were divided and fed with: 1) a chia oil diet, rich in ALA or 2) a corn oil diet, rich in linoleic acid (LA ω-6 fatty acid). Mice were subcutaneously inoculated with a tumor cell line LM3, derived from a murine mammary adenocarcinoma. RESULTS: After 35 days, tumor incidence, weight, volume and metastasis number were lower in the ALA-fed mice, while tumor latency time was higher, and the release of pro-tumor metabolites derived from ω-6 fatty acids decreased in the tumor. Compared to the control group, a lower number of mitosis, a higher number of apoptotic bodies and higher T-lymphocyte infiltration were consistently observed in the ALA group. An ALA-rich diet decreased the estrogen receptor (ER) α expression, a recognized breast cancer promotor while showing an opposite effect on ERß in tumor lysates. CONCLUSION: These data support the anticancer effect of an ALA-enriched diet, which might be used as a dietary strategy in breast cancer prevention.


Assuntos
Dieta , Neoplasias Mamárias Experimentais/patologia , Neoplasias Mamárias Experimentais/prevenção & controle , Metástase Neoplásica/prevenção & controle , Ácido alfa-Linolênico/administração & dosagem , Animais , Apoptose , Linhagem Celular Tumoral , Óleo de Milho , Receptor alfa de Estrogênio/análise , Receptor beta de Estrogênio/análise , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-6/administração & dosagem , Ácidos Graxos Ômega-6/análise , Ácidos Graxos Ômega-6/metabolismo , Feminino , Ácido Linoleico , Masculino , Neoplasias Mamárias Experimentais/química , Camundongos , Camundongos Endogâmicos BALB C , Metástase Neoplásica/patologia , Transplante de Neoplasias , Óleos de Plantas , Linfócitos T
8.
Dig Dis Sci ; 62(8): 1977-1984, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28573506

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD) increases the risk of developing colon cancer. This risk is higher in men compared to women, implicating a role for female hormones in the protection against this disease. Studies from our laboratory demonstrated that estradiol (E2) protects against inflammation-associated colon tumor formation when administered following chemical carcinogen and induction of chronic colitis. AIM: This study seeks to better understand the effect of E2 on acute colitis in the presence and absence of estrogen receptor ß (ERß). METHODS: Inflammation was induced by 2,4,6-trinitrobenzenesulfonic acid in wild-type (WT) and ERß knockout (ERßKO) mice implanted with a control or E2-containing pellet and killed 5 days later. Inflammation and injury were scored by a pathologist. Apoptosis and proliferation were assessed by immunohistochemistry. Cytokines were measured by multiplex analysis. RESULTS: E2 treatment reduced inflammation in the middle colon in WT mice and the distal colon in ERßKO mice compared to control mice. WT mice had reduced IL-6, IL-12, IL-17, GM-CSF, IFN-γ, MCP-1, MIP-1α, and TNF-α, and ERßKO had reduced IL-6 and IFN-γ expression in response to E2. Injury scores were lower in E2-treated ERßKO mice compared to control ERßKO mice. ERßKO mice had increased proliferation in the basal third of crypts in the distal colon and decreased apoptosis in the proximal colon. CONCLUSIONS: These data suggest that E2 has differential protective effects against acute colitis in the presence or absence of ERß and provide insight into how E2 may protect against IBD.


Assuntos
Colite/tratamento farmacológico , Colite/metabolismo , Estradiol/farmacologia , Receptor beta de Estrogênio/metabolismo , Estrogênios/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Colite/induzido quimicamente , Neoplasias do Colo/induzido quimicamente , Neoplasias do Colo/prevenção & controle , Citocinas/análise , Citocinas/efeitos dos fármacos , Receptor beta de Estrogênio/análise , Receptor beta de Estrogênio/genética , Feminino , Imuno-Histoquímica , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ácido Trinitrobenzenossulfônico
9.
Tumour Biol ; 37(8): 11385-95, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26968553

RESUMO

Basal-like breast cancer (BLBC) and triple-negative breast cancer (TNBC) are two entities of breast cancer that share similar poor prognosis. Even though both cancers have overlaps, there are still some differences between those two types. It has been reported that the c-Met high expression was associated with poor prognosis not only in breast cancer but also in many other cancers. The role of ERß in pathogenesis and treatment of breast cancer has remained controversial. In this study, we firstly distinguished basal-like from nonbasal-like cancer patients in TNBC patients using CK5/6 and EGFR as markers and next determined the relationship of basal-like breast cancer with c-Met or ERß expression levels and prognosis in TNBC patients. One hundred twenty-seven patients who had been diagnosed with TNBC were enrolled. The clinical and pathological characteristics of the patients were recorded. The expression of EGFR, CK5/6, ERß, and c-Met were evaluated with immunohistochemical methods using paraffin blocks. The median age of patients was 50.7 years. CK5/6 immunopositivity was 31.5 % (40/127), and EGFR was 40.2 % (51/127). Of the TNBC cases, 55.1 % (71/127) were positive for either CK5/6 or EGFR and were thus classified as basal-like breast cancer. C-Met (P < 0.001) and ERß (P = 0.002) overexpression, small tumor sizes, a ductal subtype, and high-grade tumor were significantly correlated with BLBC. High c-Met expression was detected in 43.3 % patients. Metastatic lymph nodes and tumor size (>5 cm), which were both important prognostic predictors, were significantly associated with recurrence and mortality. BLBC typically demonstrates a unique profile. CK5/6 and EGFR expression combination indicates a higher basal-like phenotype possibility. The expression of c-Met and ERß were significantly related to the basal-like phenotype. The classical markers, lymph node metastasis, and tumor size were found to have important prognostic value. However, high c-Met expression and basal-like phenotypes did not show a direct correlation with poor prognosis.


Assuntos
Biomarcadores Tumorais/análise , Receptor beta de Estrogênio/biossíntese , Proteínas Proto-Oncogênicas c-met/biossíntese , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Receptor beta de Estrogênio/análise , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Modelos de Riscos Proporcionais , Proteínas Proto-Oncogênicas c-met/análise , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/mortalidade , Adulto Jovem
10.
Eur J Vasc Endovasc Surg ; 52(1): 114-8, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27220899

RESUMO

OBJECTIVE/BACKGROUND: Chronic venous disease (CVD) is a common and relevant problem affecting Western people. The role of estrogens and their receptors in the venous wall seems to support the major prevalence of CVD in women. The effects of the estrogens are mediated by three estrogen receptors (ERs): ERα, ERß, and G protein-coupled ER (GPER). The expression of ERs in the vessel walls of varicose veins is evaluated. METHODS: In this prospective study, patients of both sexes, with CVD and varicose veins undergoing open venous surgery procedures, were enrolled in order to obtain vein samples. To obtain control samples of healthy veins, patients of both sexes without CVD undergoing coronary artery bypass grafting with autologous saphenous vein were recruited (control group). Samples were processed in order to evaluate gene expression. RESULTS: Forty patients with CVD (10 men [25%], 30 women [75%], mean age 54.3 years [median 52 years, range 33-74 years]) were enrolled. Five patients without CVD (three men, two women [aged 61-73 years]) were enrolled as the control group. A significant increase of tissue expression of ERα, ERß and GPER in patients with CVD was recorded (p < .01), which was also related to the severity of venous disease. CONCLUSION: ERs seem to play a role in CVD; in this study, the expression of ERs correlated with the severity of the disease, and their expression was correlated with the clinical stage.


Assuntos
Receptores de Estrogênio/análise , Varizes/metabolismo , Veias/química , Adulto , Idoso , Estudos de Casos e Controles , Doença Crônica , Receptor alfa de Estrogênio/análise , Receptor beta de Estrogênio/análise , Feminino , Humanos , Masculino , Memória Episódica , Pessoa de Meia-Idade , Receptores Acoplados a Proteínas G/análise
11.
Skin Pharmacol Physiol ; 29(4): 178-89, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27399919

RESUMO

Skin is a target organ of sex steroids which play important roles in skin health and disease. The aim of this study is to investigate the expression of estrogen receptor ß (ERß) and androgen receptor (AR) in human skin from different age groups for a better understanding of the hormonal regulation of skin aging. Using standard immunohistochemical techniques, biopsies of sun-unprotected and sun-protected skin were taken from 60 normal subjects. Sun-protected skin showed significantly higher immunoreactivity for ERß and AR compared to sun-unprotected skin of all age groups. Significantly higher ERß H score and percent of expression were associated with the 20-35 years age group compared to the groups that were 35-50 years and >50 years old (p < 0.02, p = 0.03, respectively) in sun-unprotected and sun-protected skin (p < 0.001, p = 0.01, respectively). AR H score showed a negative correlation with age (p = 0.04) with no significant difference in immunoreactivity in different age groups, either in sun-unprotected or sun-protected skin. There was also a significant correlation between ERß H score and epidermal thickness in sun-unprotected (p = 0.04) and sun-protected skin (p = 0.04) in studied subjects regardless of age. The same relationships did not reach significance with AR expression. However, a significant positive correlation was detected between H scores and percent of expression of ERß and AR in sun-unprotected (p = 0.01, p = 0.02, respectively) and sun-protected skin (p = 0.005, p = 0.02, respectively) regardless of age. In conclusion, both ERß and AR decline gradually with intrinsic and extrinsic aging. This decline is more obvious with extrinsic aging. Further large-scaled studies are recommended to expand, validate and translate current findings to clinically significant, diagnostic and therapeutic applications. Molecular studies to investigate the probable ligand-independent action of both receptors are warranted. In addition, their gene expression patterns and associated signaling and metabolic pathways can also be tackled to provide a basis for further interventions in pathological processes that involve their dysregulation.


Assuntos
Epiderme/metabolismo , Epiderme/patologia , Receptor beta de Estrogênio/metabolismo , Receptores Androgênicos/metabolismo , Envelhecimento da Pele/patologia , Envelhecimento da Pele/fisiologia , Adulto , Idoso , Epiderme/efeitos da radiação , Receptor beta de Estrogênio/análise , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Androgênicos/análise , Envelhecimento da Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Adulto Jovem
12.
Biochem Biophys Res Commun ; 468(1-2): 136-42, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26529545

RESUMO

Uterine leiomyomas are benign myometrial neoplasms that function as one of the common indications for hysterectomy. Clinical and biological evidences indicate that uterine leiomyomas are estrogen-dependent. Estrogen stimulates cell proliferation through binding to the estrogen receptor (ER), of which both subtypes α and ß are present in leiomyomas. Clinically, leiomyomas may be singular or multiple, where the first one is rarely recurring if removed and the latter associated to a relatively young age or genetic predisposition. These markedly different clinical phenotypes indicate that there may different mechanism causing a similar smooth muscle response. To investigate the relative expression of ERα and ERß in multiple and solitary uterine leiomyomas, we collected samples from 35 Chinese women (multiple leiomyomas n = 20, solitary leiomyoma n = 15) undergoing surgery to remove uterine leiomyomas. ELISA assay was performed to detect estrogen(E2) concentration. Quantitative real-time PCR analysis was performed to detect ERα and ERß mRNA expression. Western blot and immunohistochemical analysis were performed to detect ERα and ERß protein expression. We found that ERα mRNA and protein levels of in multiple leiomyomas were significantly lower than those of solitary leiomyomas, whereas ERß mRNA and protein levels in multiple leiomyomas were significantly higher than those in solitary leiomyomas, irrespectively of the menstrual cycle stage. In both multiple and solitary leiomyomas, ERα expression was higher than that of ERß. E2 concentration in multiple and solitary leiomyomas correlated with that of ERα expression. ERα was present in nuclus and cytoplasma while estrogen receptor ß localized only in nuclei in both multiple and solitary leiomyomas. Our findings suggest that the difference of ERα and ERß expression between multiple and solitary leiomyomas may be responsible for the course of the disease subtypes.


Assuntos
Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Leiomioma/genética , Neoplasias Uterinas/genética , Útero/patologia , Adulto , Receptor alfa de Estrogênio/análise , Receptor beta de Estrogênio/análise , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Leiomioma/patologia , Pessoa de Meia-Idade , Neoplasias Uterinas/patologia , Útero/metabolismo
13.
Cell Tissue Res ; 361(2): 605-17, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25681278

RESUMO

We report embryo-induced alterations occurring in endometrial stromal cells (ESCs) during the embryo-attachment stage in bonnet monkeys (Macaca radiata). Laser micro-dissected ESCs obtained from pregnant and non-pregnant animals were compared for levels of selected proliferation and decidualization-associated factors by analysis with quantitative real-time polymerase chain reaction or immunohistochemistry. Stromal cells exhibited extensive cellular proliferation, as indicated by cellular compaction and significantly higher (P < 0.05) levels of proliferating cell nuclear antigen and of estrogen receptor 1, c-Myc, and Cyclin D1 transcripts in pregnant animals as compared with non-pregnant animals. A significant decrease (P < 0.05) was observed in the transcript levels of stromal interleukin-6 (IL-6) in pregnant animals. Cell proliferation was accompanied by a significant increase (P < 0.001) in the levels of decidualization-associated molecules such as IL-1ß in the luminal and glandular epithelium and of stromal insulin-like growth-factor-binding protein-1 (IGFBP-1) and prostaglandin-endoperoxide synthase-2 (PTGS-2) proteins. In pregnant animals, proliferation was evident throughout the gestational stroma, whereas decidualization was more pronounced in the embryo-attachment zone than in the non-attachment zone. To our knowledge, this is the first report of alterations in the endometrial stroma during the embryo-attachment stage in a non-human primate model.


Assuntos
Implantação do Embrião , Endométrio/citologia , Macaca radiata/embriologia , Células Estromais/citologia , Animais , Proliferação de Células , Ciclina D1/análise , Ciclina D1/genética , Ciclo-Oxigenase 2/análise , Ciclo-Oxigenase 2/genética , Endométrio/metabolismo , Endométrio/ultraestrutura , Receptor alfa de Estrogênio/análise , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/análise , Receptor beta de Estrogênio/genética , Feminino , Regulação da Expressão Gênica , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/análise , Proteína 1 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Interleucina-1beta/análise , Interleucina-1beta/genética , Interleucina-6/análise , Interleucina-6/genética , Macaca radiata/genética , Gravidez , Proteínas Proto-Oncogênicas c-myc/análise , Proteínas Proto-Oncogênicas c-myc/genética , Células Estromais/metabolismo , Transcrição Gênica
14.
Eur J Gynaecol Oncol ; 36(2): 123-30, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26050347

RESUMO

PURPOSE: The natural history of human malignant melanoma suggests that steroid hormones may affect the biological behavior of this tumor. The purpose of the current study was to investigate the specific immunostaining patterns of estrogen receptors in malignant melanomas and their sentinel lymph nodes (SLNs), as well as to examine any possible association with patients' prognosis and overall survival. MATERIALS AND METHODS: A retrospective analysis of prospectively collected data was conducted during a 12-year period (2001-2012). Sixty patients with mean age of 54.4 ± 14.5 years diagnosed with melanomas of varying depth (Clark) and thickness (Breslow) after excision biopsy of pre-existing melanocytic lesions, were included in the study. All patients underwent wide excision of the primary tumor and SLN identification. Determination of estrogen receptor alpha (ERa) and beta (ERb) status by immunohistochemistry on tumor and nodal paraffin blocks was performed in all feasible cases. RESULTS: ERb but not ERa was the predominant estrogen receptor found in all primary tumors and SLNs examined. The most intense ERb immunostaining was seen in negative SLNs associated with thinner, less invading melanomas. ERb expression in the primary tumor seems to correlate with the cellular microenvironment, possibly altering the process of SLN invasion. CONCLUSIONS: ERb expression is down-regulated in aggressive melanomas with sentinel nodal metastatic disease, suggesting its possible usefulness as a surrogate marker for metastatic potential and prognosis in malignant melanoma.


Assuntos
Receptor alfa de Estrogênio/análise , Receptor beta de Estrogênio/análise , Linfonodos/química , Melanoma/química , Adulto , Idoso , Feminino , Humanos , Imuno-Histoquímica , Metástase Linfática , Masculino , Melanoma/mortalidade , Melanoma/patologia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
15.
Histochem Cell Biol ; 142(4): 421-32, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24692005

RESUMO

Estrogen signaling is considered to play an important role in spermatogenesis, spermiogenesis and male fertility. Estrogens can act via the two nuclear estrogen receptors ESR1 (ERα) and ESR2 (ERß) or via the intracellular G-protein-coupled estrogen receptor 1 (GPER, formerly GPR30). Several reports on the localization and expression of all three receptors in the human testis have been published but are controversial particularly in case of ERα. Contrary to previous studies, we decided therefore to evaluate expression of all three receptors in the testis by a number of different methods and in comparison with MCF-7 cells. Using qPCR, we could show that mRNA expression of ERα is considerably lower and expression of ERß and GPER much higher in the testis than in MCF-7 cells. RT-PCR after laser-assisted microdissection of tubular and interstitial compartments from normal and Sertoli cell only syndrome testes plus in situ hybridization and immunohistochemical analyses of the same samples demonstrated that there is very low expression of ERα in germ cells and in single interstitial cells, very high expression of ERß in germ cells and Sertoli cells and high expression of GPER in interstitial cells and less in Sertoli cells.


Assuntos
Receptor alfa de Estrogênio/análise , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/análise , Receptor beta de Estrogênio/genética , Receptores de Estrogênio/análise , Receptores de Estrogênio/genética , Receptores Acoplados a Proteínas G/análise , Receptores Acoplados a Proteínas G/genética , Testículo/metabolismo , Adulto , Humanos , Immunoblotting , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/análise , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Testículo/química , Testículo/citologia
16.
Tumour Biol ; 35(8): 7911-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24833090

RESUMO

Methylations in estrogen receptor (ER) α and ERß are known to be involved in the pathogenesis of breast cancer. Here, we explore the role of promoter methylation of estrogen receptors, ERα and ERß, in sporadic breast cancer cases from a North Indian population. To this end, association between ERα and ERß methylation status along with different clinicopathological parameters and its correlation with protein expression was examined. Four hundred eighty paired breast cancer tissue samples and adjacent normal controls from 240 sporadic breast cancer patients were included, and their clinical and demographic profiles were recorded. ERα and ERß methylation was determined by methylation-specific polymerase (MSP) chain reaction. Our findings demonstrate that methylation of ERα and ERß occurs in high frequency and appears to be a mechanism of gene silencing in our population. Furthermore, on performing stratified analysis, we observed strong associations between ERα/ERß methylation and ER, PR, and HER2 status, tumor size, clinical stage, and triple negative tumors. Thus, our study not only highlights the role of ERα/ERß methylation in breast cancer but also suggests the ERα/ERß methylation pattern as a biomarker for assessing breast cancer risk.


Assuntos
Neoplasias da Mama/genética , Metilação de DNA , Receptor alfa de Estrogênio/genética , Receptor beta de Estrogênio/genética , Regiões Promotoras Genéticas , Adulto , Idoso , Neoplasias da Mama/patologia , Receptor alfa de Estrogênio/análise , Receptor beta de Estrogênio/análise , Feminino , Humanos , Pessoa de Meia-Idade
17.
Arterioscler Thromb Vasc Biol ; 32(8): 2035-42, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22679310

RESUMO

OBJECTIVE: Our study aims to determine the role of time of menopause on vascular inflammation biomarkers and how it affects their modulation by estrogen and raloxifene in postmenopausal women. METHODS AND RESULTS: Uterine arteries from 68 postmenopausal women were divided into 3 segments and cultured for 24 hours in tissue culture media containing 17ß-estradiol (100 nmol/L), raloxifene (100 nmol/L), or vehicle. Assessment of arterial concentration of 13 inflammatory biomarkers was performed by multiplex immunobead-based assay. Aging per se has a positive correlation with the generation of several proinflammatory markers. Although short-term estradiol exposure correlates with lower expression of tumor necrosis factor-α, vascular endothelial growth factor, and interleukin-1ß in all age groups, for most biomarkers aging was associated with a switch from a beneficial anti-inflammatory action by estrogen, at earlier stages of menopause, to a proinflammatory profile after 5 years past its onset. Raloxifene has no significant effect on the expression of all proinflammatory markers. Western blot analysis of estrogen receptor expression (estrogen receptor-α and estrogen receptor-ß) showed that estrogen receptor-ß increases with aging, and this increase has a positive correlation with the generation of several proinflammatory markers. CONCLUSIONS: Aging alters estrogen-mediated effects on the modulation of inflammatory biomarkers in women. How aging affects estrogen responses on vascular inflammation is not clear, but our data show a positive association between increased estrogen receptor-ß expression with aging and proinflammatory effects by estrogen.


Assuntos
Envelhecimento/fisiologia , Estrogênios/fisiologia , Vasculite/etiologia , Adulto , Idoso , Biomarcadores , Receptor alfa de Estrogênio/análise , Receptor beta de Estrogênio/análise , Feminino , Humanos , Interleucina-6/sangue , Menopausa , Pessoa de Meia-Idade , Cloridrato de Raloxifeno/farmacologia , Fatores de Tempo
18.
Eur Rev Med Pharmacol Sci ; 17(22): 3103-10, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24302193

RESUMO

OBJECTIVES: Recently, it has been observed that weight loss is accelerated by human chorionic gonadotropin (hCG) hormone preparation used for hypothalamic dysfunction in obesity treatment in both sexes. hCG is also used for in vitro fertilization and in treatment of hypogonadotropic hypogonadism. Our aim was to observe the ultrastructural changes caused by local injections of hCG made for purpose of weight loss and to present them to inform those receiving such therapy. MATERIALS AND METHODS: In our study, 10 obese female, 10 male obese, 10 non-obese female and 10 non-obese male rats were used. In each group, single dose of subcutaneous hCG injection has been applied to 7 rats for 5 weeks in 5 days of the week, and placebo has been applied to the remaining 3 rats. Following the injection, the tissues were evaluated morphologically, immunohistochemically and ultrastructurally. RESULTS: Leptin immunoreactivity was similar in all groups. When the adipose tissue samples were examined under electron microscope, they were observed to exhibit normal structure with organelles located around the nuclei and nucleoli, and no distinctive features were found among the groups. CONCLUSIONS: Administering hCG in addition to diet had no advantage on weight reduction in rats.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Gonadotropina Coriônica/farmacologia , Tecido Adiposo/química , Tecido Adiposo/ultraestrutura , Animais , Receptor alfa de Estrogênio/análise , Receptor beta de Estrogênio/análise , Feminino , Imuno-Histoquímica , Injeções , Leptina/análise , Masculino , Microscopia Eletrônica de Transmissão , Ratos , Ratos Wistar
19.
Anim Biotechnol ; 24(4): 307-11, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23947667

RESUMO

Follicle-stimulating hormone (FSH) and luteinizing hormone (LH) have a central role in follicle growth and maturation, but no clear differences between breeds with different ovulation rates have been found. Therefore, this study investigated mRNA expression of FSHß, LHß, FSH receptor (FSHR), LH receptor (LHR), and estrogen receptor-ß (ERß) genes in prolific Lezhi black (LB) goats and nonprolific Tibetan (TB) goats by real-time PCR. Follicles and pituitaries were recovered from goats at 12-24 h after onset of estrus. Real-time PCR analysis revealed that the expression levels of FSHß and LHß mRNA were significantly higher (p < 0.01) in pituitary of LB than in TB does, but the expression levels of FSHR and LHR mRNA in follicle of TB were greater (p < 0.05). Expression level of follicular ER ß was not different between the two breeds. Data provide evidence that the greater ovulation rate in the LB goat as compared to the TB breed is associated with a greater gonadotropin expression during follicular phase.


Assuntos
Receptor beta de Estrogênio/análise , Cabras/metabolismo , Gonadotropinas Hipofisárias/análise , RNA Mensageiro/análise , Receptores da Gonadotropina/análise , Animais , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Feminino , Perfilação da Expressão Gênica , Cabras/genética , Gonadotropinas Hipofisárias/genética , Gonadotropinas Hipofisárias/metabolismo , Folículo Ovariano/química , Folículo Ovariano/metabolismo , Ovulação/genética , Ovulação/fisiologia , Hipófise/química , Hipófise/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptores da Gonadotropina/genética , Receptores da Gonadotropina/metabolismo
20.
Heart Lung Circ ; 22(2): 141-5, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23177646

RESUMO

BACKGROUND: This study was designed to investigate the effects of phytoestrogen isoflavone on balloon catheter-induced hyperplasia of carotid artery. METHODS: Forty-eight female New Zealand rabbits were randomly divided into four groups: control (balloon-induced carotid artery injury only); ovariectomy control (ovariectomy and carotid artery injury), oestrogen (ovariectomy, carotid artery injury and nilestriol, 5mg/kg daily for 28 days), and isoflavone (ovariectomy, carotid artery injury and isoflavone 120 mg/kg daily for 28 days). The arterial wall thickness was assessed by coloured ultrasonography, and the oestrogen-α and oestrogen-ß receptors in the abdominal aorta were measured by Western blotting. RESULTS: The medial layer thickness in the isoflavone group was less than in the ovariectomy control group (0.28±0.03 vs. 0.35±0.04 mm, p<0.01), and the intimal/medial layer (I/M) ratio is the isoflavone group was also less than in the ovariectomy control group (16.85±3.79 vs. 48.94±8.92, p<0.01). There was no statistically significant difference in the medial layer thickness or I/M ratio between the isoflavone and the oestrogen groups. The optical density of the oestrogen-α receptors in the isoflavone group (0.317±0.002) was less than in the oestrogen (0.633±0.002) or ovariectomy control group (0.590±0.001, p<0.01). The optical density of the oestrogen-ß receptors in the isoflavone group (1.350±0.002) and the ovariectomy control group (1.2033±0.002) was less than in the oestrogen group (1.7699±0.003, p<0.01). CONCLUSIONS: Isoflavone therapy in the ovariectomised rabbit model attenuated balloon catheter-induced intimal and medial layer hyperplasia in the carotid arteries. Down-regulation of the oestrogen-α receptors may be involved in the hyperplasia-preventative effect.


Assuntos
Artérias Carótidas/patologia , Isoflavonas/uso terapêutico , Fitoestrógenos/uso terapêutico , Túnica Íntima/patologia , Animais , Artérias Carótidas/diagnóstico por imagem , Cateterismo/efeitos adversos , Proteínas de Drosophila/química , Receptor alfa de Estrogênio/análise , Receptor beta de Estrogênio/análise , Proteínas do Olho/química , Feminino , Hiperplasia/diagnóstico por imagem , Hiperplasia/tratamento farmacológico , Hiperplasia/etiologia , Proteínas do Tecido Nervoso/química , Ovariectomia , Coelhos , Glycine max , Túnica Íntima/diagnóstico por imagem , Ultrassonografia Doppler em Cores
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