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3.
Pediatrics ; 145(2)2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31974216

RESUMO

BACKGROUND AND OBJECTIVES: Gonadotropin-releasing hormone analogues are commonly prescribed to suppress endogenous puberty for transgender adolescents. There are limited data regarding the mental health benefits of this treatment. Our objective for this study was to examine associations between access to pubertal suppression during adolescence and adult mental health outcomes. METHODS: Using a cross-sectional survey of 20 619 transgender adults aged 18 to 36 years, we examined self-reported history of pubertal suppression during adolescence. Using multivariable logistic regression, we examined associations between access to pubertal suppression and adult mental health outcomes, including multiple measures of suicidality. RESULTS: Of the sample, 16.9% reported that they ever wanted pubertal suppression as part of their gender-related care. Their mean age was 23.4 years, and 45.2% were assigned male sex at birth. Of them, 2.5% received pubertal suppression. After adjustment for demographic variables and level of family support for gender identity, those who received treatment with pubertal suppression, when compared with those who wanted pubertal suppression but did not receive it, had lower odds of lifetime suicidal ideation (adjusted odds ratio = 0.3; 95% confidence interval = 0.2-0.6). CONCLUSIONS: This is the first study in which associations between access to pubertal suppression and suicidality are examined. There is a significant inverse association between treatment with pubertal suppression during adolescence and lifetime suicidal ideation among transgender adults who ever wanted this treatment. These results align with past literature, suggesting that pubertal suppression for transgender adolescents who want this treatment is associated with favorable mental health outcomes.


Assuntos
Hormônio Liberador de Gonadotropina/análogos & derivados , Saúde Mental , Puberdade/efeitos dos fármacos , Ideação Suicida , Pessoas Transgênero/psicologia , Adolescente , Adulto , Fatores Etários , Análise de Variância , Intervalos de Confiança , Estudos Transversais , Feminino , Identidade de Gênero , Acesso aos Serviços de Saúde , Humanos , Masculino , Razão de Chances , Puberdade/psicologia , Inquéritos e Questionários/estatística & dados numéricos , Pessoas Transgênero/estatística & dados numéricos , Adulto Jovem
4.
Theriogenology ; 142: 260-267, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31711700

RESUMO

The effect of different treatment agents, namely, carp pituitary homogenate (CPH), Ovaprim ([D-Arg6, Pro9NEt]-sGnRH + domperidone) and a dopamine-receptor antagonist (metoclopramide), on the stimulation of northern pike (Esox lucius) spermiation was tested under controlled conditions. To carry out the experiment, males (n = 84) were divided into four groups: control (n = 21); CPH (n = 21); Ovaprim (n = 21); metoclopramide (n = 21). The control group was given 0.9% NaCl but no hormonal treatment. After 24 h, sperm was collected from seven males belonging to control (n = 7), CPH (n = 7), Ovaprim (n = 7) and metoclopramide (n = 7). This procedure was repeated after 48 and 72 h post-treatment. At each time, sperm was collected from seven males from each group only once. After collection, the quantity and quality of sperm were determined. It was confirmed that the treatment agent and latency time (the time between treatment and sperm collection) are two factors affecting the quantity and quality of northern pike sperm collected under controlled conditions. The highest total sperm volume and total sperm production (TSP) were noted in the CPH group compared to the Ovaprim, metoclopramide and control groups. In contrast, the time of sperm collection affected the sperm concentration (SC), TSP and sperm pH. With increasing time, SC and TSP decreased, which indicated the occurrence of sperm hydration being part of the final sperm maturation process. Sperm maturation is in turn a consequence of increases in sperm pH and seminal plasma osmotic pressure between 48 and 72 h post-treatment. Sperm motility and sperm kinetic parameters were affected by treatment agent and the time of sperm collection. This indicates that the sperm's ability to move that is achieved in the optimal environment (in spermatic ducts) is dependent on both factors which determine sperm maturation in northern pike under controlled condition.


Assuntos
Domperidona/farmacologia , Esocidae , Hormônio Liberador de Gonadotropina/farmacologia , Metoclopramida/farmacologia , Hipófise/química , Espermatozoides/efeitos dos fármacos , Extratos de Tecidos/farmacologia , Animais , Carpas , Combinação de Medicamentos , Esocidae/fisiologia , Hormônio Liberador de Gonadotropina/análogos & derivados , Masculino , Análise do Sêmen , Motilidade Espermática/efeitos dos fármacos , Espermatogênese/efeitos dos fármacos , Espermatozoides/fisiologia , Fatores de Tempo
5.
Nan Fang Yi Ke Da Xue Xue Bao ; 39(10): 1207-1212, 2019 Oct 30.
Artigo em Chinês | MEDLINE | ID: mdl-31801718

RESUMO

OBJECTIVE: To compare the effects of cetrorelix and ganirelix in gonadotropin-releasing hormone antagonist (GnRH-ant) cycles for preventing premature luteinizing hormone (LH) surges and on clinical outcomes of IVF-ET cycles. METHODS: We retrospectively analyzed 2572 GnRH-ant cycles of in vitro fertilization and embryo transfer from January, 2013 to December, 2016, including 1368 cycles with cetrorelix treatment and 1204 cycles with ganirelix treatment. The baseline characteristics of the patients and the clinical outcomes of the two groups were compared. RESULTS: Compared with those receiving ganirelix treatment, the patients with cetrorelix treatment had a significantly younger age (33.10 vs 33.89 years, P < 0.001) and a lower body mass index (21.57 vs 21.84 kg/m2, P=0.024). After adjustment for age and body mass index of the patients, no significant differences were found between the two groups in the levels of follicle-stimulating hormone (FSH), LH, estradiol (E2), progesterone (P) levels either at the baseline or on the day of hCG triggering, or in the number of oocytes retrieved (P > 0.05). The two groups also had comparable percentages of patients with LH > 10 U/L on the day of hCG triggering (3.7% vs 3.2%) and similar spontaneous ovulation rate (0.6% vs 0.5%), clinical pregnancy rate (47.7% vs 45.9%) and live birth rate (37.5% vs 33.6%) following fresh embryo transfer (P > 0.05). The incidence of moderate to severe ovarian hyperstimulation syndrome, however, was significantly higher in ganirelix group than in cetrorelix group (0.7% vs 0.1%, P=0.006). CONCLUSIONS: Cetrorelix and ganirelix can achieve comparable effects for preventing premature LH surges and can achieve similar clinical outcomes of GnRH-ant cycles, but ganirelix is associated with a significantly higher incidence of moderate to severe ovarian hyperstimulation syndrome.


Assuntos
Fertilização In Vitro , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Antagonistas de Hormônios/uso terapêutico , Hormônio Luteinizante/fisiologia , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Hormônio Luteinizante/sangue , Gravidez , Taxa de Gravidez , Estudos Retrospectivos , Resultado do Tratamento
6.
Clinics (Sao Paulo) ; 74: e1205, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31721934

RESUMO

OBJECTIVE: There are no doubts about the clinical benefits of treatment with GnRH analogs for patients diagnosed with central precocious puberty (CPP). However, laboratory monitoring of CPP is still a matter of considerable controversy in the literature. Therefore, the main objective of this study was to evaluate the cut-off values of stimulated LH that determine gonadotrophic suppression. METHODS: Twenty-four girls, on treatment with leuprorelin acetate (LA) at 3.75 mg IM every 28 days, were studied. The clinical parameters used to indicate clinical effectiveness were regression or maintenance of sexual characteristics according to the Tanner stage, growth velocity reduction, reduction or maintenance of the difference between bone age and chronological age and maintenance or improvement of the final height prediction. For the laboratory effectiveness test, basal estradiol, LH, and FSH levels were collected before and 1 and 2 h after the administration of 3.75 mg LA. RESULTS: Eleven girls showed improvement in all clinical parameters, and their effectiveness tests were compared to those of the other patients to calculate the cut-off values, which were ≤3.64 IU/L (p=0.004*) for LH after 1 h and ≤6.10 IU/L (p<0.001*) for LH after 2 h. CONCLUSION: The LH response after the LA stimulation test, associated with clinical data and within a context of CPP, constitutes a reliable and feasible resource and can assist in monitoring the effectiveness of treatment.


Assuntos
Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/uso terapêutico , Leuprolida/uso terapêutico , Puberdade Precoce/tratamento farmacológico , Estudos de Casos e Controles , Criança , Feminino , Hormônio Liberador de Gonadotropina/análogos & derivados , Humanos , Masculino , Puberdade Precoce/sangue , Resultado do Tratamento
7.
Int J Mol Sci ; 20(22)2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31739545

RESUMO

The unicellular Tetrahymena distinguishes structure-related vertebrate hormones by its chemosensory reactions. In the present work, the selectivity of hormone receptors was evaluated by analyzing the effects of various gonadotropin-releasing hormone (GnRH) analogs (GnRH-I, GnRH-III) as well as truncated (Ac-SHDWKPG-NH2) and dimer derivatives ([GnRH-III(C)]2 and [GnRH-III(CGFLG)]2) of GnRH-III on (i) locomotory behaviors, (ii) cell proliferation, and (iii) intracellular hormone contents of Tetrahymena pyriformis. The migration, intracellular hormone content, and proliferation of Tetrahymena were investigated by microscope-assisted tracking analysis, flow cytometry, and a CASY TT cell counter, respectively. Depending on the length of linker sequence between the two GnRH-III monomers, the GnRH-III dimers had the opposite effect on Tetrahymena migration. [GnRH-III(CGFLG)]2 dimer had a slow, serpentine-like movement, while [GnRH-III(C)]2 dimer had a rather linear swimming pattern. All GnRH-III derivatives significantly induced cell growth after 6 h incubation. Endogenous histamine content was uniformly enhanced by Ac-SHDWKPG-NH2 and GnRH-III dimers, while some differences between the hormonal activities of GnRHs were manifested in their effects on intracellular levels of serotonin and endorphin. The GnRH peptides could directly affect Tetrahymena migration and proliferation in a structure-dependent manner, and they could indirectly regulate these reactions by paracrine/autocrine mechanisms. Present results support the theory that recognition ability and selectivity of mammalian hormone receptors can be deduced from a phylogenetically ancient level like the unicellular Tetrahymena.


Assuntos
Hormônio Liberador de Gonadotropina/metabolismo , Hormônios/metabolismo , Tetrahymena pyriformis/efeitos dos fármacos , Tetrahymena pyriformis/fisiologia , Sequência de Aminoácidos , Proliferação de Células , Fatores Quimiotáticos , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/química , Hormônio Liberador de Gonadotropina/farmacologia
8.
Bull Exp Biol Med ; 168(1): 52-54, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31741247

RESUMO

We studied the effect of gonadotropin-releasing hormone agonist surfagon (2 µg/kg, once, intraperitoneally) on anxious behavior of adult gonadectomized and non-gonadectomized male rats. It was shown that surfagon significantly increased anxiety of both gonadectomized and non-gonadectomized rats in the open-field test and in elevated plus maze.


Assuntos
Hormônio Liberador de Gonadotropina/análogos & derivados , Animais , Ansiedade/metabolismo , Comportamento Animal/efeitos dos fármacos , Hormônio Foliculoestimulante/metabolismo , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Liberador de Gonadotropina/farmacologia , Hormônio Luteinizante/metabolismo , Masculino , Ratos , Testosterona/metabolismo
9.
Int J Mol Sci ; 20(20)2019 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-31614426

RESUMO

Head and neck squamous cell carcinomas (HNSCC) have a high mortality rate, although several potential therapeutic targets have already been identified. Gonadotropin-releasing hormone receptor (GnRH-R) expression is less studied in head and neck cancers, hence, we investigated the therapeutic relevance of GnRH-R targeting in HNSCC patients. Our results indicate that half of the patient-derived samples showed high GnRH-R expression, which was associated with worse prognosis, making this receptor a promising target for GnRH-based drug delivery. Photodynamic therapy is a clinically approved treatment for HNSCC, and the efficacy and selectivity may be enhanced by the covalent conjugation of the photosensitizer to a GnRH-R targeting peptide. Several native ligands, gonadotropin-releasing hormone (GnRH) isoforms, are known to target GnRH-R effectively. Therefore, different 4Lys(Bu) modified GnRH analogs were designed and conjugated to protoporphyrin IX. The receptor binding potency of the novel conjugates was measured on human pituitary and human prostate cancer cells, indicating only slightly lower GnRH-R affinity than the peptides. The in vitro cell viability inhibition was tested on Detroit-562 human pharyngeal carcinoma cells that express GnRH-R in high levels, and the results showed that all conjugates were more effective than the free protoporphyrin IX.


Assuntos
Neoplasias de Cabeça e Pescoço/metabolismo , Peptídeos/administração & dosagem , Protoporfirinas/química , Receptores LHRH/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Regulação para Cima , Adulto , Idoso , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/análogos & derivados , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Peptídeos/química , Peptídeos/farmacologia , Fotoquimioterapia , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Análise de Sobrevida , Análise Serial de Tecidos , Regulação para Cima/efeitos dos fármacos
10.
Histochem Cell Biol ; 152(6): 423-437, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31630211

RESUMO

Wide application of gonadotropin-releasing hormone (GnRH) agonists and antagonists for clinical purposes determines their effects on ovarian signaling pathways. Our study aimed to determine the localization, expression levels of Wnt signaling members in the pubertal and adult mouse ovary and the impact of GnRH antagonist cetrorelix on these signaling members. 0.5 mg/kg of cetrorelix was injected to 3-and 6-week-old mice for 2 weeks. At the end of injection, ovaries from 5 (5Ce)- to 8-week (8Ce)-old mice were embedded in paraffin for immunohistochemistry and homogenized for western blot to compare with control (5C-8C) and sham groups (5S-8S). WNT2 and WNT4 showed higher expression in thecal and stromal cells in adult mouse ovaries and only WNT4 expression was affected by cetrorelix. FZD1 was localized mainly in oocytes of pubertal ovaries and granulosa cells and oocytes of adult ovaries. FZD1 was reduced by cetrorelix in pubertal ovaries. FZD4 was abundantly localized in thecal and stromal cells of all groups and protein level was not affected by cetrorelix. LRP-6 was expressed mainly in oocytes and stromal cells of pubertal, oocytes of adult ovaries and its expression was reduced by cetrorelix in adult ovaries. CTNNB1 intensity in granulosa cells was the lowest in pubertal and the highest in adult ovaries and its expression was decreased by cetrorelix in adult ovaries. Cetrorelix affected the expression of specific members of the Wnt signaling depending on the developmental stage of mice, pointing out its possible interaction with gonadotropins during pubertal and adult stages.


Assuntos
Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Antagonistas de Hormônios/farmacologia , Oócitos/efeitos dos fármacos , Puberdade/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos , Animais , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/química , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Liberador de Gonadotropina/farmacologia , Antagonistas de Hormônios/administração & dosagem , Antagonistas de Hormônios/química , Camundongos , Camundongos Endogâmicos BALB C , Oócitos/metabolismo , Puberdade/metabolismo
11.
J Pediatr Endocrinol Metab ; 32(12): 1369-1375, 2019 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-31605579

RESUMO

Background The standard treatment of central precocious puberty (CPP) is gonadotropin-releasing hormone analogues (GnRHa). It is a concern that children treated with GnRHa are at risk of developing obesity which could impair the treatment outcomes. This study aimed to investigate the effect of GnRHa on body mass index (BMI) standard deviation score (SDS), and the influence of BMI status on treatment outcomes in children with idiopathic CPP (iCPP). Methods A retrospective cohort study in children with iCPP who completed GnRHa treatment and had attained near final adult height (NFAH) was conducted. Children with a history of disease or drug ingestion which could affect their BMI were excluded. BMI, BMI SDS, height (Ht), Ht SDS, predicted adult height (PAH), and NFAH were compared at baseline, 1 and 2 years during treatment, and at NFAH according to the baseline BMI status; normal weight and overweight/obesity. Results Fifty-eight children with iCPP treated with GnRHa were enrolled. The BMI SDS was significantly increased at 1 and 2 years during treatment in the overweight/obese group and at 1 year during treatment in the normal-weight group. However, at NFAH (2 years after treatment discontinuation), the BMI SDS was not statistically different from baseline in both groups. Ht gain, change in Ht SDS and BMI SDS were not statistically different from the baseline in both groups. Conclusions GnRHa results in a transient increase in BMI SDS during treatment and returned to baseline after treatment cessation. The benefit of GnRHa treatment on final Ht improvement is similar between overweight/obese and normal-weight patients.


Assuntos
Estatura , Peso Corporal , Hormônio Liberador de Gonadotropina/administração & dosagem , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Puberdade Precoce/tratamento farmacológico , Adulto , Estudos de Casos e Controles , Criança , Feminino , Hormônio Liberador de Gonadotropina/análogos & derivados , Humanos , Masculino , Prevalência , Puberdade Precoce/epidemiologia , Puberdade Precoce/patologia , Estudos Retrospectivos , Resultado do Tratamento
12.
Int J Mol Sci ; 20(18)2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31491902

RESUMO

This study aimed to investigate the effect of gonadotropin-releasing hormone agonist (GnRHa) treatment on the expression of neuritin 1 (NRN1) in women with ovarian endometriosis. We collected tissues and serum from women with endometriosis treated with (n = 45) or without (n = 37) GnRHa. NRN1 mRNA and protein levels were measured using qPCR and Western blot. Immunolocalization of NRN1 in endometriotic tissues was examined using immunohistochemistry. In addition, a follow-up study was carried out to monitor the serum level of NRN1 in patients before and after GnRHa treatment. Both mRNA (p = 0.046) and protein (p = 0.0155) levels of NRN1 were significantly lower in endometriotic tissues from patients receiving GnRHa treatment compared to the untreated group. Both epithelial and stromal cells of endometriotic tissues from untreated women with endometriosis exhibited stronger staining of NRN1 but not in those who were treated with GnRHa. The follow-up study showed that the serum level of the NRN1 concentration decreased significantly from 1149 ± 192.3 to 379.2 ± 80.16 pg/mL after GnRHa treatment (p = 0.0098). The expression of NRN1 was significantly lower in women with ovarian endometriosis treated with GnRHa. These results suggest that NRN1 may be a biomarker response to the effect of GnRHa treatment for patients with ovarian endometriosis.


Assuntos
Endometriose/etiologia , Endometriose/metabolismo , Hormônio Liberador de Gonadotropina/agonistas , Neuropeptídeos/genética , Ovário/patologia , Adulto , Biomarcadores , Biópsia , Endometriose/tratamento farmacológico , Endometriose/patologia , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/farmacologia , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Pessoa de Meia-Idade , Neuropeptídeos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Adulto Jovem
13.
Int J Mol Sci ; 20(18)2019 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-31500399

RESUMO

The wide range of cellular target reactions (e.g., antitumor) of gonadotropin-releasing hormone (GnRH) variants provides the possibility to develop multifunctional GnRH conjugates. The aim of our work was to compare the cytotoxic/apoptotic activity of different GnRH-based, daunorubicin (Dau)-linked conjugates with or without butyrated Lys in position 4 (4Lys(Bu)) at a molecular level in a human colorectal carcinoma cell line. Cell viability was measured by impedimetry, cellular uptake and apoptosis were studied by flow cytometry, and the expression of apoptosis-related genes was analyzed by qRT-PCR. The modification with 4Lys(Bu) resulted in an increased cytotoxic and apoptotic effects and cellular uptake of the GnRH-I and GnRH-III conjugates. Depending on the GnRH isoform and the presence of 4Lys(Bu), the conjugates could regulate the expression of several apoptosis-related genes, especially tumor necrosis factor (TNF), tumor protein p53 (TP53) and the members of growth-factor signaling. The stronger cytotoxicity of GnRH-I and GnRH-III conjugates containing 4Lys(Bu) was associated with a stronger inhibitory effect on the expression of growth-factor signaling elements in comparison with their 4Ser counterparts, in which the upregulation of TP53 and caspases (e.g., CASP9) seemed to play a more important role. We were able to provide further evidence that targeting the GnRH receptor could serve as a successful therapeutic approach in colon cancer, and GnRH-III-[4Lys(Bu),8Lys(Dau=Aoa)] proved to be the best candidate for this purpose.


Assuntos
Antineoplásicos Hormonais/farmacologia , Apoptose/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/farmacologia , Animais , Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/genética , Biologia Computacional/métodos , Daunorrubicina/análogos & derivados , Daunorrubicina/farmacologia , Relação Dose-Resposta a Droga , Perfilação da Expressão Gênica , Humanos , Transcriptoma
14.
Reprod Biol ; 19(3): 245-254, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31383475

RESUMO

Granulosa Cells (GCs) are sensitive to excessive production of reactive oxygen species (ROS). Quercetin (QUR) is a free radical scavenger which can alleviate oxidative stress through nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/antioxidant response element (ARE) pathway and thioredoxin (Trx) system. We aimed to explore the probable protective role of QUR on cultured human GCs treated with hydrogen peroxide (H2O2) as an inducer of oxidative stress. MTT assay was applied for evaluating the cell cytotoxicity of QUR and H2O2. The rate of apoptotic cells and intracellular ROS generation were determined by Annexin V-FITC/PI staining and 2'-7'-dichlorodihydrofluorescein diacetate fluorescent probes (DCFH-DA), respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis and western blot analysis were used to evaluate the gene and protein expression of Nrf2 and kelch-like ech-associated protein 1 (Keap1)1. The Nrf2 and Trx activities were measured by Enzyme-linked Immunosorbent Assay (ELISA). The results indicated that QUR pretreatment can decrease ROS production and apoptosis induced by H2O2. In addition, QUR increased Nrf2 gene and protein expression, as well as its nuclear translocation. Moreover, in QUR-treated group, a lower level of Keap1 protein was observed, which was not reported as significant. The results also indicated a significant correlation between the expression of Nrf2 and Keap1 in QUR-treated group. Further, QUR protected GCs from oxidative stress by increasing Trx gene expression and activity. This study suggests that QUR as a supplementary factor may protect GCs from oxidative stress in diseases related to this condition.


Assuntos
Células da Granulosa/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Quercetina/farmacologia , Tiorredoxinas/metabolismo , Adulto , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/farmacologia , Estrogênios/sangue , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Fármacos para a Fertilidade Feminina/farmacologia , Hormônio Foliculoestimulante Humano/administração & dosagem , Hormônio Foliculoestimulante Humano/farmacologia , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/farmacologia , Humanos , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Tiorredoxinas/genética , Adulto Jovem
15.
Recenti Prog Med ; 110(7): 347-355, 2019.
Artigo em Italiano | MEDLINE | ID: mdl-31379370

RESUMO

LHRH analogues (LHRHa) are used in the treatment of breast cancer that occurs in young women. Amenorrhoea induced by chemotherapy correlates with a reduced risk of recurrence disease. In premenopausal women, analogous LHRHs are used to suppress ovarian estrogen production, raising estrogen hormone levels to post-menopausal values and improving patient outcomes. Two large clinical studies have investigated the role of complete estrogen blockage in adjuvant hormonal treatment of premenopausal patients. Both studies showed the clinical benefit of ovarian suppression treatment, mainly associated with non-steroidal aromatase inhibitor exemestane in high-risk patients. In the recent years, hormonal treatments made available in clinical practice have considerably prolonged the median survival of patients suffering from endocrine-responsive metastatic breast cancer. Even in the premenopausal setting, CDK4/6 inhibitors in association with endocrine therapy have shown a marked improvement in patient outcomes. The safety and efficacy of this new class of drugs demonstrated in the MONALEESA-7 study in premenopausal women and in the premenopausal subgroups of the PALOMA-3 and MONARCH 2 studies support the use of hormone therapy and analogous LHRH combined with CDK 4/6 inhibitor in patients in premenopausal. Finally, LHRH analogues have been extensively studied in strategies for maintaining ovarian function and fertility preservation during adjuvant chemotherapy in younger patients.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Pré-Menopausa , Antineoplásicos Hormonais/efeitos adversos , Antineoplásicos Hormonais/farmacologia , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/efeitos adversos , Inibidores da Aromatase/farmacologia , Neoplasias da Mama/patologia , Quimioterapia Adjuvante/métodos , Feminino , Preservação da Fertilidade , Hormônio Liberador de Gonadotropina/análogos & derivados , Humanos
16.
J Sep Sci ; 42(18): 3033-3040, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31257725

RESUMO

Alarelin, a gonadotropin-releasing hormone analogue, is widely used in China for the treatment of endometriosis and uterine leiomyoma. In order to investigate its pharmacokinetic behavior and support the preclinical application of new formulations, we have developed a novel and highly selective bioanalytical method to determine alarelin in rat plasma based on liquid chromatography tandem mass spectrometry with triple stage fragmentation. After sample preparation by protein precipitation followed by reversed phase solid phase extraction, alarelin and triptorelin (internal standard) were chromatographed on an Ascentis® Express C18 column (50 mm × 4.6 mm, 2.7 µm) using gradient elution with 0.1% formic acid in water and acetonitrile at a flow rate of 1 mL/min. Detection was by positive mode electrospray ionization followed by triple stage fragmentation using the transitions at m/z 584.6→249.1→221.0 for alarelin and 656.5→249.1→176.0 for triptorelin, The assay was linear in the concentration range 0.3-10 ng/mL with excellent precision and accuracy. It was successfully applied to a pharmacokinetic study in rats administered a dose of 13.5 µg/kg alarelin by intramuscular injection. The results show that the triple stage fragmentation strategy allows highly selective analysis of alarelin and has the potential to be widely applied to the bioassay of other peptidic drugs.


Assuntos
Hormônio Liberador de Gonadotropina/análogos & derivados , Peptídeos/farmacologia , Pamoato de Triptorrelina/farmacocinética , Animais , Cromatografia Líquida , Feminino , Hormônio Liberador de Gonadotropina/sangue , Hormônio Liberador de Gonadotropina/química , Hormônio Liberador de Gonadotropina/farmacocinética , Masculino , Estrutura Molecular , Peptídeos/sangue , Peptídeos/química , Ratos , Ratos Wistar , Extração em Fase Sólida , Espectrometria de Massas em Tandem , Pamoato de Triptorrelina/sangue , Pamoato de Triptorrelina/química
17.
Theriogenology ; 136: 95-100, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31254727

RESUMO

The aim of the present study was to evaluate the efficacy of a GnRH analog for induction of ovulation in Brazilian Northeastern jennies (Equus asinus) with different follicle diameters. Four consecutive estrus of 10 jennies were used in a crossover study; C (Control, n = 10) jennies were evaluated by transrectal palpation and ultrasonography until a spontaneous ovulation and the intervals between the predetermined follicular size (25-28 mm [C1], 29-32 mm [C2] and 33-36 mm [C3] follicle) and ovulation were registered. In treated cycle, jennies had the ovulation induced by 250 µg of Histrelin acetate (Strelin®, Botupharma, Botucatu, Brazil) when respective follicle diameters 25-28 mm (T1), 29-32 mm (T2) and 33-36 mm (T3) were diagnosed. Ovulation was monitored by transrectal palpation and ultrasonography. Different follicle diameters significantly affected (P < 0.05) the interval until ovulation between control and matched treated cycles. Interval between prostaglandin administration and ovulation diagnosis was lower in jennies from T2 group (145.2 ±â€¯34.6 h) compared with the control cycle (220.0 ±â€¯41.8 h) and also with other treated cycles (T1 - 209.8 ±â€¯48.0 h; T3 - 183.3 ±â€¯33.9 h). Histrelin acetate treatment also reduces the interval between detection of predetermined follicular size and ovulation (P < 0.05) in all treated cycles groups compared with matched control group. Higher percentage (P < 0.05) of jennies had success of ovulation induction (36-48 h after Histrelin acetate injection) in all treated cycles in contrast with the matched control group. In addition, in comparison among treated cycle groups, more (P < 0.05) jennies (100%) in T2 ovulated between 36 and 48 h after ovulation induction, compared with T1 and T3, which did not differ (P > 0.05) from each other. Edema scoring and ovulation were not associated events (r = 0.0219). In conclusion, jennies with 29-32 mm follicles satisfactory responded to ovulation induction with Histrelin acetate, which allowed the shortening of interovulatory interval in all groups evaluated.


Assuntos
Equidae , Hormônio Liberador de Gonadotropina/análogos & derivados , Folículo Ovariano/efeitos dos fármacos , Ovulação/efeitos dos fármacos , Animais , Brasil , Feminino , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/farmacologia , Folículo Ovariano/fisiologia
19.
Reprod Biol ; 19(2): 179-188, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31151754

RESUMO

Corpus luteum (CL) is an endocrine tissue involved in regulation of reproductive cycle and early pregnancy establishment. In the present study DEAD-box helicase-5 (Ddx5), a member of the DEAD box family of RNA helicases was investigated for its expression, regulation and function in CL of Wistar rats. Ddx5 was expressed in adult rat CL. Primary cell culture from supra-ovulated ovaries were established for in vitro studies. Addition of luteinizing hormone (LH; 100 ng/ml), a luteotrophic factor in primary cell culture, decreased Ddx5 RNA expression (foldchange:0.6 ±â€¯0.075) while prostaglandin alpha (PGF2α; 1µM), a luteolytic factor caused an increase (foldchange:2.4 ±â€¯0.4) compared to control group. Under in vivo conditions, the administration of PGF2α or gonadotropin-releasing hormone antagonist; cetrorelix (CET) caused luteolysis as well as an increase in the protein level of Ddx5 (foldchange:1.9 ±â€¯0.27 and 1.4 ±â€¯0.09 viz.; p < 0.05) in CL of adult rats. LH was administered post CET treatment which suppressed Ddx5 protein expression (foldchange:0.8 ±â€¯0.16; p < 0.05) compared to CET treated group. Further, it was observed that the expression of Ddx5 was upregulated (foldchange:1.5 ±â€¯0.23; p < 0.05) in CL during late pregnancy compared to mid pregnancy concomitant to luteolysis in adult rats. Overall, the results suggest for the first time that Ddx5 is expressed in rat CL and regulated by luteolytic and luteotrophic factors in an inverse fashion. Further, the data significantly correlates ddx5 expression to CL regression suggesting involvement of ddx5 in luteolysis. These results suggest a significant role of Ddx5 in female reproduction biology and warrant in depth examination of the function of Ddx5 in CL.


Assuntos
Cloprostenol/farmacologia , Corpo Lúteo/metabolismo , RNA Helicases DEAD-box/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio Liberador de Gonadotropina/análogos & derivados , Animais , Gonadotropina Coriônica/farmacologia , RNA Helicases DEAD-box/genética , Feminino , Hormônio Liberador de Gonadotropina/farmacologia , Antagonistas de Hormônios/farmacologia , Luteolíticos/farmacologia , Gravidez , Ratos , Ratos Wistar
20.
Curr Med Sci ; 39(3): 431-436, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31209815

RESUMO

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in women. Progestin-primed ovarian stimulation (PPOS) protocol, which used oral progestin to prevent premature luteinizing hormone (LH) surges in ovarian stimulation, has been proved to be effective and safe in patients with PCOS. The aim of the present study was to compare the efficacy of PPOS protocol with that of the traditional gonadotropin-releasing hormone (GnRH) antagonist protocol in patients with PCOS. A total of 157 patients undergoing in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) were recruited into this study. The patients were divided into two groups by the stimulation protocols: the GnRH antagonist protocol group and the PPOS protocol group. There was no significant difference in the clinical characteristics between the two groups. Dose and duration of gonadotropin were higher in the PPOS protocol group. Estradiol levels on the day of human chorionic gonadotropin (hCG) administration were significantly lower in the PPOS protocol group. Fertilization rates and the number of good quality embryos were similar between the two groups. Remarkably, we found 6 patients with moderate ovarian hyperstimulation syndrome (OHSS) in the GnRH antagonist protocol group but 0 in the PPOS protocol group. A total of 127 women completed their frozen embryo transfer (FET) cycles. There were no significant differences between the two groups in terms of clinical pregnancy rate per transfer, implantation rate, first-trimester miscarriage rate and on-going pregnancy rate per transfer. To conclude, PPOS protocol decreased the incidence of OHSS without adversely affecting clinical outcomes in patients with PCOS.


Assuntos
Fármacos para a Fertilidade Feminina/uso terapêutico , Hormônio Liberador de Gonadotropina/análogos & derivados , Antagonistas de Hormônios/uso terapêutico , Infertilidade Feminina/terapia , Indução da Ovulação/métodos , Síndrome do Ovário Policístico/fisiopatologia , Progestinas/administração & dosagem , Adulto , Gonadotropina Coriônica/administração & dosagem , Transferência Embrionária/métodos , Estradiol/sangue , Feminino , Fertilização In Vitro/métodos , Expressão Gênica , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Hormônio Liberador de Gonadotropina/genética , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Infertilidade Feminina/complicações , Infertilidade Feminina/diagnóstico , Infertilidade Feminina/fisiopatologia , Masculino , Síndrome de Hiperestimulação Ovariana/induzido quimicamente , Síndrome de Hiperestimulação Ovariana/diagnóstico , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Ovário/efeitos dos fármacos , Ovário/metabolismo , Ovário/fisiopatologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/diagnóstico , Gravidez , Taxa de Gravidez , Progestinas/efeitos adversos , Estudos Prospectivos , Injeções de Esperma Intracitoplásmicas/métodos , Resultado do Tratamento
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