RESUMO
Batch spawner fishes develop successive clutches of oocytes which allows them to participate in many reproductive cycles during their adult life (iteroparous) and spawn in multiple events within each breeding cycle. Here, ovarian follicular development was morpho-functionally analyzed in females of the iteroparous batch spawner fish Gymnocorymbus ternetzi. To obtain better insights into the reproductive morpho-physiology in batch spawners, the objective of this research was to analyze the dynamics of the follicular development, with its hormonal regulation between two active reproduction events. We found that over 16 days, follicles progressed asynchronously to chromatin nucleolus, Primary and Secondary growth stages of oogenesis with progressive secretion of 17ß-estradiol (E2). During the end of secondary growth, the increase in 17α,20ß-dihydroxy-4-pregnen-3-one (17,20ß-p) was measured relative to the maturation process of the ovarian follicles (e.g., nuclear migration and its rupture during the resumption of meiosis). Interestingly, an additional increase in E2 was observed after fish reproduction, probably related to the recruitment of new batch follicles for secondary growth. We also measured the high values of multiple condition factor post-reproduction measurements, reflecting more energy invested during the pre-reproductive process. We also quantified high concentrations of 17,20ß-p, probably related to the recruitment of a new batch of oogonia to meiosis, presumably secreted by post-ovulatory follicles, after fish reproduction. We finally found that fish without exposure to reproductive stimulus developed a regression phase at day 24, characterized by massive follicle atresia, that allow them to recycle energy and constitutive materials of the follicles invested during oogenesis for another reproductive cycle.
Assuntos
Estradiol , Folículo Ovariano , Ovulação , Animais , Feminino , Folículo Ovariano/fisiologia , Estradiol/metabolismo , Ovulação/fisiologia , Oogênese/fisiologia , Reprodução , HidroxiprogesteronasRESUMO
Objectives Strategies to prevent preterm birth are limited. 17 Alpha-Hydroxyprogesterone Caproate (17P) injections have been shown to be effective, but the intervention is under-used. This mixed methods study investigates barriers and facilitators to 17P administration among Medicaid and CHIP participants enrolled in Strong Start for Mothers and Newborns, a federal preterm birth prevention program. Methods Twenty-seven awardees with more than 200 sites in 30 states, the District of Columbia, and Puerto Rico enrolled approximately 46,000 women in Strong Start from 2013 to 2016. Participant data, including data on preterm birth and 17P, was collected for each woman. Intensive interviews (n = 211) conducted with Strong Start program staff and providers (n = 314) included questions about 17P provision. Results Of women whose data included a valid response regarding 17P initiation, 3919 had a prior preterm birth and current singleton pregnancy; 14.95% received 17P. Barriers to 17P administration include late entry to prenatal care, administrative burden of preauthorization, cost risks to providers, limits in scope of practice for non-physician providers, and social barriers among participants. Facilitators for provision include streamlined work flows and the option of home administration. Conclusions for Practice A universal insurance authorization process could mitigate many barriers to 17P use. Providers need continuing education regarding the effectiveness of 17P, and expanding scope of practice for non-physician prenatal care providers would increase access. Targeted program interventions can help to overcome social barriers Medicaid participants face in accessing care. Streamlined work processes and the option of home health services are two effective program-based facilitators for providing 17P to a Medicaid population.
Assuntos
Hidroxiprogesteronas/administração & dosagem , Medicaid/estatística & dados numéricos , Nascimento Prematuro/prevenção & controle , Cuidado Pré-Natal/métodos , Caproato de 17 alfa-Hidroxiprogesterona , Adulto , District of Columbia , Feminino , Disparidades em Assistência à Saúde , Humanos , Recém-Nascido , Mães , Gravidez , Porto Rico , Fatores Socioeconômicos , Estados UnidosRESUMO
BACKGROUND: Infants born <37 weeks' gestation are of public health concern since complications associated with preterm birth are the leading cause of mortality in children <5 years of age and a major cause of morbidity and lifelong disability. The administration of 17-alpha hydroxyprogesterone caproate reduces preterm birth by 33% in women with history of spontaneous preterm birth. We demonstrated previously that plasma concentrations of 17-alpha hydroxyprogesterone caproate vary widely among pregnant women and that women with 17-alpha hydroxyprogesterone caproate plasma concentrations in the lowest quartile had spontaneous preterm birth rates of 40% vs rates of 25% in those women with higher concentrations. Thus, plasma concentrations are an important factor in determining drug efficacy but the reason 17-alpha hydroxyprogesterone caproate plasma concentrations vary so much is unclear. Predominantly, 17-alpha hydroxyprogesterone caproate is metabolized by CYP3A4 and CYP3A5 enzymes. OBJECTIVE: We sought to: (1) determine the relation between 17-alpha hydroxyprogesterone caproate plasma concentrations and single nucleotide polymorphisms in CYP3A4 and CYP3A5; (2) test the association between progesterone receptor single nucleotide polymorphisms and spontaneous preterm birth; and (3) test whether the association between plasma concentrations of 17-alpha hydroxyprogesterone caproate and spontaneous preterm birth varied by progesterone receptor single nucleotide polymorphisms. STUDY DESIGN: In this secondary analysis, we evaluated genetic polymorphism in 268 pregnant women treated with 17-alpha hydroxyprogesterone caproate, who participated in a placebo-controlled trial to evaluate the benefit of omega-3 supplementation in women with history of spontaneous preterm birth. Trough plasma concentrations of 17-alpha hydroxyprogesterone caproate were measured between 25-28 weeks of gestation after a minimum of 5 injections of 17-alpha hydroxyprogesterone caproate. We extracted DNA from maternal blood samples and genotyped the samples using TaqMan (Applied Biosystems, Foster City, CA) single nucleotide polymorphism genotyping assays for the following single nucleotide polymorphisms: CYP3A4*1B, CYP3A4*1G, CYP3A4*22, and CYP3A5*3; and rs578029, rs471767, rs666553, rs503362, and rs500760 for progesteronereceptor. We adjusted for prepregnancy body mass index, race, and treatment group in a multivariable analysis. Differences in the plasma concentrations of 17-alpha hydroxyprogesterone caproate by genotype were evaluated for each CYP single nucleotide polymorphism using general linear models. The association between progesterone receptor single nucleotide polymorphisms and frequency of spontaneous preterm birth was tested using logistic regression. A logistic model also tested interaction between 17-alpha hydroxyprogesterone caproate concentrations with each progesterone receptor single nucleotide polymorphism for the outcome of spontaneous preterm birth. RESULTS: The association between CYP single nucleotide polymorphisms *22, *1G, *1B, and *3 and trough plasma concentrations of 17-alpha hydroxyprogesterone caproate was not statistically significant (P = .68, .44, .08, and .44, respectively). In an adjusted logistic regression model, progesterone receptor single nucleotide polymorphisms rs578029, rs471767, rs666553, rs503362, and rs500760 were not associated with the frequency of spontaneous preterm birth (P = .29, .10, .76, .09, and .43, respectively). Low trough plasma concentrations of 17-alpha hydroxyprogesterone caproate were statistically associated with a higher frequency of spontaneous preterm birth (odds ratio, 0.78; 95% confidence ratio, 0.61-0.99; P = .04 for trend across quartiles), however no significant interaction with the progesterone receptor single nucleotide polymorphisms rs578029, rs471767, rs666553, rs503362, and rs500760 was observed (P = .13, .08, .10, .08, and .13, respectively). CONCLUSION: The frequency of recurrent spontaneous preterm birth appears to be associated with trough 17-alpha hydroxyprogesterone caproate plasma concentrations. However, the wide variation in trough 17-alpha hydroxyprogesterone caproate plasma concentrations is not attributable to polymorphisms in CYP3A4 and CYP3A5 genes. Progesterone receptor polymorphisms do not predict efficacy of 17-alpha hydroxyprogesterone caproate. The limitations of this secondary analysis include that we had a relative small sample size (n = 268) and race was self-reported by the patients.
Assuntos
Citocromo P-450 CYP3A/genética , Hidroxiprogesteronas/sangue , Polimorfismo de Nucleotídeo Único , Nascimento Prematuro/sangue , Nascimento Prematuro/genética , Receptores de Progesterona/genética , Caproato de 17 alfa-Hidroxiprogesterona , Adulto , Feminino , Idade Gestacional , Humanos , Hidroxiprogesteronas/administração & dosagem , Gravidez , Progestinas/administração & dosagemRESUMO
BACKGROUND: Midtrimester ultrasound is a valuable method for identifying asymptomatic women at risk for spontaneous preterm delivery (PTD). However, response to various treatments (cerclage, progestogen) has been variable in the clinical setting. It remains unclear how other biomarkers may be used to guide intervention strategies. OBJECTIVE: We applied an amniotic fluid inflammatory scoring system to determine if the degree of inflammation is associated with intervention efficacy in patients with midtrimester short cervix. STUDY DESIGN: Women carrying a singleton fetus between 16-24 weeks' gestation with a short cervix (≤25 mm) on transvaginal ultrasound underwent amniocentesis and were assigned to McDonald cerclage, no cerclage, or weekly 17-alpha hydroxyprogesterone caproate (17OHP-C). Our previously described inflammatory risk score (comprised of 14 inflammatory markers) was used to classify patients as high (score ≥8) or low (score <8) risk for inflammation. Gestational age at delivery was compared for each intervention and risk score status. Risk of delivering as a function of the remaining gestation was evaluated using modified Cox proportional hazards models with incorporation of methods to account for both left and right truncation bias. RESULTS: Ninety patients were included: 24 were in the nonintervention control group, 51 received cerclage, and 15 received 17OHP-C. Inflammation status at time of sampling influenced the efficacy of the treatment (P < .001). Compared to the nonintervention control group, in patients with low inflammation (score < 8), both cerclage (adjusted hazard ratio [HR], 2.86; 95% confidence interval [CI], 1.28-6.37) and 17OHP-C (HR, 3.11; 95% CI, 1.04-9.30) were associated with increased hazard of PTD. In contrast, in patients with high inflammation (score ≥8) both cerclage (HR, 0.22; 95% CI, 0.08-0.65) and 17OHP-C (HR, 0.20; 95% CI, 0.05-0.81) were associated with lower hazard of delivering preterm. CONCLUSION: Cerclage placement or administration of 17OHP-C therapy for midtrimester short cervix for PTD prevention appears beneficial only in the subset of patients with high inflammation. Knowledge of the amniotic fluid inflammatory status may aid in guiding the appropriate therapy for women presenting with midtrimester short cervix who are at increased risk of PTD.
Assuntos
Líquido Amniótico/imunologia , Cerclagem Cervical/métodos , Colo do Útero/diagnóstico por imagem , Citocinas/imunologia , Hidroxiprogesteronas/uso terapêutico , Gravidez , Nascimento Prematuro/prevenção & controle , Caproato de 17 alfa-Hidroxiprogesterona , Adulto , Amniocentese , Medida do Comprimento Cervical , Quimiocina CCL2/imunologia , Quimiocina CCL3/imunologia , Quimiocina CCL4/imunologia , Feminino , Fator Estimulador de Colônias de Granulócitos/imunologia , Humanos , Inflamação , Interleucinas/imunologia , Segundo Trimestre da Gravidez , Nascimento Prematuro/imunologia , Progestinas , Modelos de Riscos Proporcionais , Medição de Risco , Resultado do Tratamento , Fator de Necrose Tumoral alfa/imunologia , Adulto JovemRESUMO
Potamodromous teleosts that require migration to reproduce show dysfunctions that block ovulation and spawning while in captivity. To understand the physiological basis of these reproductive dysfunctions, follicle-stimulating hormone b subunit (fshb) and luteinizing hormone b subunit (lhb) gene expression analyses by real-time quantitative PCR, together with measurements of estradiol (E 2), 17α-hydroxyprogesterone (17α-OHP) and 17α,20ß-dihydroxy-4-pregnen-3-one (17α,20ß-DHP) levels, were carried out throughout the reproductive cycle of the potamodromous Salminus hilarii. The following reproductive stages were evaluated in captive and wild females: previtellogenic (PV), advanced maturation/mature (AM) and regression/spent (REG/SPENT). In the wild females, fshb expression decreased from the PV to the AM stage, and the opposite pattern was detected for E 2, which increased from the PV to the AM stage. fshb was expressed at lower levels in captive than in wild females, and this difference did not change during the reproductive cycle. lhb expression also increased from the PV to the AM stage in both groups, but the wild females at the AM and REG/SPENT stages showed higher lhb expression levels than the captive females. The concentrations of 17α-OHP did not change during the reproductive cycle, and the levels were higher in the captive than in the wild females at all reproductive stages. 17α,20ß-DHP levels did not change between wild and captive females. However, in captive females, the transition from PV to AM stage was followed by an increase in 17α,20ß-DHP levels. These data indicate that dysfunctions in the gonadotropins and steroids synthesis pathways cause the ovulation failure in captive S. hilarii.
Assuntos
Characidae/fisiologia , Hormônios Esteroides Gonadais/fisiologia , Gonadotropinas/fisiologia , Ovário/fisiopatologia , Ovulação , 17-alfa-Hidroxiprogesterona/sangue , Animais , Estradiol/sangue , Feminino , Hormônio Foliculoestimulante/fisiologia , Hidroxiprogesteronas/sangue , Hormônio Luteinizante/fisiologiaRESUMO
El presente estudio investiga la utilidad de determinar puntos de corte ajustados según la edad gestacional y el peso al nacer de neonatos (2-100 días) en la cuantificación de 17-hidroxiprogesterona en muestras de sangre seca en papel de filtro. Se analizaron los resultados de 6.266 determinaciones realizadas en el marco del Programa Nacional de Fortalecimiento de la Detección Precoz de Enfermedades Congénitas. Los datos se dividieron en cuatro grupos; Grupo 1: recién nacido pretérmino con bajo peso; Grupo 2: recién nacido pretérmino con peso normal; Grupo 3: recién nacido a término con bajo peso y Grupo 4: recién nacido a término con peso normal. Se establecieron puntos de corte diferentes a partir del cálculo del percentilo 99 de la distribución de frecuencias. Basado en este análisis se realizó la comparación de la tasa de resultados falsos positivos que se obtuvieron según el punto de corte establecido por el fabricante y los obtenidos en el estudio. Los nuevos puntos de corte obtenidos fueron: 217,72 nmol/L, 102,14 nmol/L, 61,62 nmol/L y 82,38 nmol/L para los grupos 1, 2, 3 y 4 respectivamente. Se evidenció una tasa total de falsos positivos del 1% con los nuevos puntos de corte, significativamente menor a la tasa del 6,2% obtenida al utilizar el punto de corte del fabricante. Esto puso en evidencia que el uso de puntos de corte adecuadamente establecidos para la población en estudio reduce significativamente las complicaciones derivadas de las repeticiones de análisis y eventualmente la tasa de recitaciones, lo cual es una importante contribución a la Salud Pública.
The present work studies the usefulness of determining adjusted cut-offs for the quantification of 17-hydroxyprogesterone in dried blood samples on filter paper, taking into account the gestational age and weight of the neonates. The results of 6266 determinations made within the framework of the National Program of Strengthening Early Detection of Congenital Disease were analysed. Data were divided into groups, Group 1: early established from the calculation of the 99 percentiles of the frequency distribution. New cutoff points were: 217.72 nmol/L, 102.14 nmol/L, 61.62 nmol/L and 82.38 nmol/L for groups 1, 2, 3 and 4 respectively. It showed a total rate of 1% false positives with the new cut-off points, which was significantly lower than the rate of 6.2% obtained using the manufacturer's cutoff. This revealed that the use of properly established cut-offs for the study of population reduces significantly the complications derived fromn analysis repetitions and eventually the recitation rate, which is an important contribution to Public Health.
O presente estudo investiga a utilidade de determinar pontos de corte estabelecidos conforme a idade gestacional e o peso ao nascer de neonatos (2-100 dias) na quantificação da 17-hidroxiprogesterona em amostras de sangue seco em papel filtro. Foram analisados os resultados de 6.266 determinações feitas no âmbito do Programa Nacional de Fortalecimento da Detecção Precoce de Doenças Congênitas. Os dados foram divididos em quatro grupos; Grupo 1: recém-nascido pré-termo com baixo peso, Grupo 2: recém-nascido pré-termo com peso normal, Grupo 3: recém-nascido a termo com baixo peso e Grupo 4: recém-nascido a termo com peso normal e foram estabelecidos pontos de corte diferentes a partir do cálculo do percentil 99 da distribuição de frequências. Com base nesta análise foi realizada a comparação da taxa de resultados falsos positivos obtidos conforme o ponto de corte estabelecido pelo fabricante e os obtidos no estudo. Os novos pontos de corte obtidos foram: 217,72 nmol/L, 102,14 nmol/L, 61,62 nmol/L e 82,38 nmol/L para os grupos 1, 2, 3 e 4, respectivamente. Tornou-se evidente uma taxa total de 1% de falsos positivos, com os novos pontos de corte significativamente menor do que a taxa de 6,2% obtida utilizando o ponto de corte do fabricante. Isto revelou que o uso de pontos de corte de forma adequada estabelecidos para a população em estudo reduz significativamente as complicações decorrentes das repetições de análises e eventualmente a taxa de repetição de novos encontros, o que é uma importante contribuição para a saúde pública.
Assuntos
Humanos , Masculino , Feminino , Recém-Nascido , 17-alfa-Hidroxiprogesterona/análise , 17-alfa-Hidroxiprogesterona/sangue , Hiperplasia Suprarrenal Congênita , Hiperplasia Suprarrenal Congênita/sangue , Doenças e Anormalidades Congênitas, Hereditárias e Neonatais , Doenças Genéticas Inatas , HidroxiprogesteronasRESUMO
OBJECTIVE: The aim of this study was to examine the effects of 17-alpha-hydroxyprogesterone caproate (17OHP-C) on the activity and expression of several common hepatic cytochrome P450 (CYP) enzymes. STUDY DESIGN: Primary human hepatocytes were pretreated with vehicle or 17OHP-C (0.1 and 1 µmol/L) for 72 hours, then incubated for 1 hour with a cocktail of CYP substrates. The activity of various CYP enzymes was determined by measuring the formation of the metabolites of specific CYP substrates, using liquid chromatography-tandem mass spectrometry. The messenger RNA expression of various CYP enzymes was determined by real-time polymerase chain reaction. RESULTS: In primary cultures of human hepatocytes, 17OHP-C minimally altered the activity or messenger RNA levels of CYP1A2, CYP2C9, CYP2D6, and CYP3A. However, 17OHP-C at 1 µmol/L increased CYP2C19 activity by 2.8-fold (P < .01) and CYP2C19 expression by 2.4-fold (P < .001), compared with vehicle-treated cells. A strong positive correlation between activity and expression of CYP2C19 was also observed (r = 0.9, P < .001). CONCLUSION: The activity and expression of hepatic CYP2C19 was significantly increased by 17OHP-C in primary cultures of human hepatocytes. This suggests that exposure to medications that are metabolized by CYP2C19 may be decreased in pregnant patients receiving 17OHP-C. Metabolism of substrates of CYP1A2, CYP2C9, CYP2D6, and CYP3A are not expected to be altered in patients receiving 17OHP-C.
Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Hepatócitos/efeitos dos fármacos , Hidroxiprogesteronas/farmacologia , Progestinas/farmacologia , Caproato de 17 alfa-Hidroxiprogesterona , Biomarcadores/metabolismo , Células Cultivadas , Cromatografia Líquida , Citocromo P-450 CYP2C19/metabolismo , Interações Medicamentosas , Hepatócitos/metabolismo , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Espectrometria de Massas em TandemRESUMO
OBJECTIVE: The purpose of this study was to evaluate the quality of compounded 17-hydroxyprogesterone caproate (17-OHPC). STUDY DESIGN: Compounded 17-OHPC that was obtained from 15 compounding pharmacies throughout the United States was analyzed for potency, impurities, sterility, and pyrogen status. RESULTS: Eighteen samples were supplied by 15 compounding pharmacies. The concentration of 17-OHPC in all samples was within the specification limits, and all tested samples passed sterility and pyrogen testing. Only 1 of 18 samples was out of specification limits for impurities. CONCLUSION: Compounded 17-OHPC that was obtained from 15 pharmacies throughout the United States did not raise safety concerns when assessed for potency, sterility, pyrogen status, or impurities.
Assuntos
Composição de Medicamentos/normas , Hidroxiprogesteronas/normas , Caproato de 17 alfa-Hidroxiprogesterona , Humanos , Hidroxiprogesteronas/análise , Pirogênios , Garantia da Qualidade dos Cuidados de Saúde , Controle de Qualidade , Estados UnidosRESUMO
OBJECTIVE: 17-alpha hydroxyprogesterone caproate 250 mg weekly reduces recurrent spontaneous preterm birth in women with a prior spontaneous preterm birth by 33%. The dose is not based on pharmacologic considerations. A therapeutic concentration has not been determined hampering any attempt to optimize treatment. This study evaluated the relationship between 17-alpha hydroxyprogesterone caproate plasma concentrations and the rate of spontaneous preterm birth in women with singleton gestation. STUDY DESIGN: A single blood sample was obtained between 25 and 28 weeks' gestation from 315 women with a spontaneous preterm birth who participated in a placebo-controlled, prospective, randomized clinical trial evaluating the benefit of omega-3 supplementation in reducing preterm birth. All women in the parent study received 17-alpha hydroxyprogesterone caproate and 434 received omega-3 supplementation and 418 received a placebo. Plasma from 315 consenting women was analyzed for 17-alpha hydroxyprogesterone caproate concentration. RESULTS: There were no differences between placebo and omega-3 supplemented groups in demographic variables, outcomes or in mean 17-alpha hydroxyprogesterone caproate concentration. Plasma concentrations of 17-alpha hydroxyprogesterone caproate ranged from 3.7-56 ng/mL. Women with plasma concentrations of 17-alpha hydroxyprogesterone caproate in the lowest quartile had a significantly higher risk of spontaneous preterm birth (P = .03) and delivered at significantly earlier gestational ages (P = .002) than did women in the second to fourth quartiles. The lowest preterm birth rates were seen when median 17-alpha hydroxyprogesterone caproate concentrations exceeded 6.4 ng/mL. CONCLUSION: Low plasma 17-alpha hydroxyprogesterone caproate concentration is associated with an increased risk of spontaneous preterm birth. This finding validates efficacy of this treatment but suggests that additional studies are needed to determine the optimal dosage.
Assuntos
Ácidos Graxos Ômega-3/uso terapêutico , Hidroxiprogesteronas/sangue , Nascimento Prematuro/sangue , Caproato de 17 alfa-Hidroxiprogesterona , Feminino , Humanos , Hidroxiprogesteronas/administração & dosagem , Gravidez , Segundo Trimestre da Gravidez/sangue , Nascimento Prematuro/prevenção & controle , RecidivaRESUMO
OBJECTIVE: We sought to evaluate in women with twin gestation the relationship between 17-hydroxyprogesterone caproate (17-OHPC) concentration and gestational age at delivery and select biomarkers of potential pathways of drug action. STUDY DESIGN: Blood was obtained between 24-28 weeks (epoch 1) and 32-35 weeks (epoch 2) in 217 women with twin gestation receiving 17-OHPC or placebo. Gestational age at delivery and concentrations of 17-OHPC, 17-hydroxyprogesterone, progesterone, C-reactive protein (CRP), and corticotrophin-releasing hormone were assessed. RESULTS: Women with higher concentrations of 17-OHPC delivered at earlier gestational ages than women with lower concentrations (P < .001). Women receiving 17-OHPC demonstrated significantly higher (P = .005) concentrations of CRP in epoch 1 than women receiving placebo but CRP values were similar in epoch 2 in both groups. A highly significant (P < .0001) positive relationship was observed between 17-OHPC concentration and progesterone and 17-hydroxyprogesterone concentrations at both epochs. Corticotropin-releasing hormone concentrations did not differ by treatment group. CONCLUSION: 17-OHPC may adversely impact gestational age at delivery in women with twin gestation.
Assuntos
Idade Gestacional , Hidroxiprogesteronas/efeitos adversos , Gravidez de Gêmeos/efeitos dos fármacos , Nascimento Prematuro/tratamento farmacológico , Progestinas/efeitos adversos , Caproato de 17 alfa-Hidroxiprogesterona , 17-alfa-Hidroxiprogesterona/sangue , Adulto , Biomarcadores/sangue , Proteína C-Reativa/análise , Hormônio Liberador da Corticotropina/sangue , Feminino , Humanos , Hidroxiprogesteronas/administração & dosagem , Hidroxiprogesteronas/sangue , Gravidez , Nascimento Prematuro/prevenção & controle , Progesterona/sangue , Progestinas/administração & dosagem , Progestinas/sangue , Resultado do TratamentoRESUMO
River damming and building of hydroelectric power plants interrupt the reproductive migration routes and change the major physicochemical parameters of water quality, with drastic consequences for populations of migratory fishes. The goal of this study was to evaluate proliferation and cell death during spermatogenesis and serum profiles of sex steroids in Prochilodus argenteus, from the São Francisco River, downstream from the Três Marias Dam. A total of 257 adult males were caught quarterly during a reproductive cycle in two sites: the first 34 km of the river after the dam (site 1) and the second 34-54 km after the dam (site 2), after the confluence with a tributary, the Abaeté River. Seasonal changes in the testicular activity associated with morphometric analyses of germ cells as well as proliferation and testicular apoptosis support a more active spermatogenesis in fish from site 2, where higher levels of sex steroids and gonadosomatic index (GSI) were also found. In site 1, fish presented low serum levels of testosterone, 17ß-estradiol and 17α-hydroxyprogesterone and a low GSI during gonadal maturation. Spermatogonial proliferation (PCNA) and apoptosis (TUNEL) were more elevated in fish from site 1, but spermatocytes were mainly labelled in fish from site 2. Overall, these data demonstrate changes in testicular activity and plasma sex steroids in a neotropical teleost fish living downstream from a hydroelectric dam, supplying new data on fish reproduction in regulated rivers. Moreover, morphometric analyses associated with sex steroids profiles provide reliable tools to assess fish spermatogenesis under environmental stress conditions.
Assuntos
Peixes/fisiologia , Reprodução/fisiologia , Estações do Ano , Espermatogênese/fisiologia , Esteroides/sangue , Animais , Brasil , Estradiol/sangue , Peixes/sangue , Hidroxiprogesteronas/sangue , Masculino , Centrais Elétricas , Rios , Testosterona/sangueRESUMO
The mechanism by which some hydrophobic molecules such as steroids and free fatty acids (FFA) act as noncompetitive inhibitors of the nicotinic acetylcholine receptor (AChR) is still not known. In the present work, we employ Förster resonance energy transfer (FRET) between the intrinsic fluorescence of membrane-bound Torpedo californica AChR and the fluorescent probe Laurdan using the decrease in FRET efficiency (E) caused by steroids and FFA to identify potential sites of these hydrophobic molecules. Structurally different steroids produced similar changes (DeltaE) in FRET, and competition studies between them demonstrate that they occupy the same site(s). They also share their binding site(s) with FFA. Furthermore, the FRET conditions define the location of the sites at the lipid-protein interface. Endogenous production of FFA by controlled phospholipase A2 enzymatic digestion of membrane phospholipids yielded DeltaE values similar to those obtained by addition of exogenous ligand. This finding, together with the preservation of the sites in membranes subjected to controlled proteolysis of the extracellular AChR moiety with membrane-impermeable proteinase K, further refines the topology of the sites at the AChR transmembrane domain. Agonist-induced desensitization resulted in the masking of the sites observed in the absence of agonist, thus demonstrating the conformational sensitivity of FFA and steroid sites in the AChR.
Assuntos
Sítios de Ligação/efeitos dos fármacos , Ácidos Graxos não Esterificados/farmacologia , Receptores Nicotínicos/química , Esteroides/farmacologia , 2-Naftilamina/análogos & derivados , Animais , Ácido Araquidônico/farmacologia , Cortisona/farmacologia , Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes , Hidrocortisona/farmacologia , Hidroxiprogesteronas/farmacologia , Lauratos , Fosfolipases A/metabolismo , Fosfolipases A2 , Conformação Proteica/efeitos dos fármacos , Receptores Nicotínicos/efeitos dos fármacos , TorpedoRESUMO
The mouse model of schistosomal periportal fibrosis (Symmers' "pipestem" fibrosis), that develops in 30-50% of the infected animals, is not reproduced in undernourished mice. Host nutritional status is likely to be a variable that may influence the outcome and progression of infection, since it interferes with the dynamics of connective tissue changes occurring in chronic hepatic schistosomiasis. Re-infections increase the occurrence of periportal liver fibrosis in well-nourished animals, but it is not known how undernourished mice would behave being repeatedly re-infected. So, 21-day-old male albino Swiss mice were individually exposed to 30 cercariae (percutaneous route) of the BH strain of Schistosoma mansoni, 4 weeks after being on a low-protein diet. Control animals were fed on a commercial balanced chow for mice. The nutritional status was evaluated by body weight gain and measurement of food intake. Mice were divided into four groups: A1 (undernourished, single infected), A2 (well-nourished, single infected), B1 (undernourished, re-infected), B2 (well-nourished, re-infected). The primary infection was performed 4 weeks after ingesting the respective diet. Re-infections started 45 days later, with exposure to 15 cercariae, at 15 day intervals. Mice were sacrificed 18 weeks after the primary exposure. The livers were submitted to morphological (gross and microscopic pathology), morphometric (percentage of fibrosis; granuloma size; volume and numerical densities) by using semi-automatic morphometry, and biochemical (quantification of collagen as hydroxyproline) studies. Worm burdens and hepatic egg counting were also recorded. Values for body weight gains were always lower in undernourished mice, the effects of re-infection being minimal on this regard. Liver and spleen weights were higher in well-nourished mice (either single infected or re-infected) and mainly related to the type of ingested diet. A greater number of re-infected well-nourished mice developed periportal fibrosis, but undernourished re-infected animals did not reproduce this lesion. The percentage of fibrosis and hepatic collagen content were higher in well-nourished mice, but differences between single infected and re-infected groups were not statistically significant.
Assuntos
Cirrose Hepática/parasitologia , Desnutrição Proteico-Calórica/parasitologia , Schistosoma mansoni/crescimento & desenvolvimento , Esquistossomose mansoni/parasitologia , Animais , Peso Corporal , Histocitoquímica , Hidroxiprogesteronas/metabolismo , Fígado/parasitologia , Cirrose Hepática/metabolismo , Masculino , Camundongos , Tamanho do Órgão , Contagem de Ovos de Parasitas , Desnutrição Proteico-Calórica/metabolismo , Esquistossomose mansoni/metabolismo , Baço/parasitologiaRESUMO
The present study employs an in vitro system to analyse the role of steroid hormones in hCG-induced spermiation in two species of anuran amphibian: Rana catesbeiana and Leptodactylus ocellatus. In vitro spermiation was induced with 10 IU hCG and the effect of different steroid-biosynthesis inhibitors was analysed. Cyanoketone (10(-5)M), an inhibitor of 3-oxo-4-ene steroid biosynthesis, did not block hCG-inducing activity even when biosynthesis of androgen was significantly reduced. These results clearly showed that, in both species, spermiation-inducing action of hCG does not depend on the biosynthesis of 3-oxo-4-ene steroids. Moreover, when combined inhibitors, aminoglutethimide (10(-5)M) plus cyanoketone (10(-5)M), were employed, spermiation evoked by hCG was not modified while hCG-induced androgen secretion significantly decreased. Additionally, none of the steroids used, progesterone, 17, 20 alpha-dihydroxy-4-pregnen-3-one, testosterone and 5 alpha-dihydrotestosterone, were able to induce spermiation in the absence of hCG, confirming that steroids are not involved in that process. In conclusion, as previously described in Bufo arenarum, in L. ocellatus and R. catesbeiana hCG-induced spermiation does not depend on steroid biosynthesis.
Assuntos
Anuros/fisiologia , Rana catesbeiana/fisiologia , Espermatogênese , Esteroides/biossíntese , Androgênios/metabolismo , Animais , Gonadotropina Coriônica/farmacologia , Di-Hidrotestosterona/farmacologia , Humanos , Hidroxiprogesteronas/farmacologia , Masculino , Progesterona/farmacologia , Testosterona/farmacologiaRESUMO
The purpose of the present study was to evaluate the effect of 4-pregnen-17-hydroxy-3-one (A) and two steroids homologues: 3beta-acetoxy-5,16-pregnadien-20-one (B) and 3beta-acetoxy-16alpha-17alpha-epoxy-4-pregnen-20-one (C). Male Wistar rats were treated with o-cresol combined (A, B or C) steroids. Lipid peroxidation status as result of measurement reactive substances to thiobarbituric acid (TBARS) as well as serotonin (5-HT) and its precursor 5-hydroxytryptophan (5-HTP) were measured. The prostate glands were weighed, the 5alpha-reductase activity was determined. The animals treated with A, B, and C steroids showed a slight increase in both 5alpha-reductase activity and prostate size. 5-HT and 5-HTP levels did not change significantly, and TBARS showed an increase in the group treated with B steroid and a decrease in the A steroid group with significant differences in both groups (p<0.05) versus control group. Results suggest that A steroid reduces TBARS in rat brain, perhaps as a result of the interaction between the testosterone unsaturated carbons and OH(-) groups with free radicals.
Assuntos
Encéfalo/efeitos dos fármacos , Hidroxiprogesteronas/farmacologia , Peroxidação de Lipídeos/efeitos dos fármacos , Pregnenodionas/farmacologia , Testosterona/farmacologia , 5-Hidroxitriptofano/metabolismo , Animais , Encéfalo/metabolismo , Colestenona 5 alfa-Redutase/metabolismo , Cresóis/farmacologia , Masculino , Tamanho do Órgão , Próstata/efeitos dos fármacos , Próstata/metabolismo , Próstata/patologia , Ratos , Ratos Wistar , Serotonina/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/análiseRESUMO
We studied the glucocorticoid response to the synthetic steroid pregna-1,4-diene-11beta-ol-3,20-dione (DeltaHOP) in several cell types and correlated its biological effect with the ability of the glucocorticoid receptor (GR) to be retained in the nuclear compartment. We observed that the DeltaHOP-transformed GR was diffusely distributed in the nucleus compared to the discrete structures observed for the dexamethasone (DEX)-transformed GR. Despite the fact that the receptor was entirely nuclear upon binding of each steroid and exhibited identical nuclear export rates, a greater amount of DeltaHOP-transformed GR was recovered in the cytoplasmic fraction after hypotonic cell lysis. Furthermore, accelerated nuclear export of GR was evidenced in digitonin-permeabilized cells treated with ATP and molybdate. Inasmuch as limited trypsinization of DEX-GR and DeltaHOP-GR complexes yielded different proteolytic products, we conclude that GR undergoes a differential conformational change upon binding of each ligand. We propose that these conformational differences may consequently lead to changes of stability in the interaction of the GR with chromatin. Therefore, the dynamic exchange of liganded GR with chromatin is likely to have significant consequences for the observed pleiotropic physiological responses triggered by glucocorticoid ligands, not only in different tissues but also in the same cell type.
Assuntos
Compartimento Celular/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Células Eucarióticas/efeitos dos fármacos , Glucocorticoides/farmacologia , Receptores de Glucocorticoides/agonistas , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Transporte Ativo do Núcleo Celular/genética , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Compartimento Celular/fisiologia , Divisão Celular/efeitos dos fármacos , Divisão Celular/fisiologia , Núcleo Celular/genética , Núcleo Celular/metabolismo , Células Cultivadas , Dexametasona/metabolismo , Dexametasona/farmacologia , Endométrio/efeitos dos fármacos , Endométrio/metabolismo , Células Eucarióticas/citologia , Células Eucarióticas/metabolismo , Feminino , Glucocorticoides/metabolismo , Hidroxiprogesteronas/metabolismo , Hidroxiprogesteronas/farmacologia , Masculino , Camundongos , Conformação Molecular , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/genética , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo , Proteína bcl-XRESUMO
The jundiá Rhamdia quelen (Quoy and Gaimard) is a teleost species from the Siluridae family and is an important species for aquaculture in temperate and subtropical climates. Gonad and blood tissue samples were taken from cultured jundiá females between 1998 and 1999. Plasma concentrations of 17beta-estradiol (E(2)), testosterone (T), 11-ketotestosterone (11-KT), 17-hydroxy-4-pregnene-3,20-dione (17-P), 17,20beta-dihydroxy-4-pregnen-3-one (17,20beta-P), and 17,20beta,21-trihydroxy-4-pregnen-3-one (20beta-S) were measured by radioimmunoassay and potential correlations with the stage of oogenesis and sexual maturation examined. During the experimental period two spawning episodes were observed. Plasma concentrations of E(2) increased progressively during oocyte development, simultaneously with the appearance of yolk vesicles and increasing amounts of deposited yolk. In female jundiá, the T peak occurred in October and was coincident with the peak in gonadosomatic index. Two distinct peaks of progestogens were detected, corresponding to the two spawning episodes, suggesting that one or more of these steroids might act as the "maturational-inducing steroid" in jundiá. Unusually large amounts of 11-KT were also measured in the plasma of mature jundiá females. The identity of 11-KT was confirmed by thin-layer chromatography. Although the profiles of the other steroids are compatible with the roles proposed for the action of these hormones in other teleosts, the role of 11-KT, normally found only in males, is unknown.
Assuntos
Cortodoxona/análogos & derivados , Peixes/sangue , Reprodução , Esteroides/sangue , Testosterona/análogos & derivados , Animais , Clima , Cortodoxona/sangue , Estradiol/sangue , Feminino , Peixes/crescimento & desenvolvimento , Hidroxiprogesteronas/sangue , Oogênese , Pregnenodionas/sangue , Estações do Ano , Maturidade Sexual , Testosterona/sangueRESUMO
Los síndromes de hiperandrogenismo de diferente grado constituyen un motivo de consulta frecuente en un consultorio de Ginecología Infantojuvenil. Estos cuadros suelen provocar preocupación en las adolescentes tanto por sus manifestaciones estéticas (hirsutismo, acné, alopecía) como por la presencia de alteraciones del ciclo mestrual que puede crearles dudas sobre su fertilidad futura. Una de las causas de hiperandrogenismo, la Hiperplasia Adrenal Congénita No Clásica (HACNC), cobra importancia debido a su origen genético y a que no existen elementos de la clínica que permitan diferenciarla de otras etiologías como síndrome de ovarios poliquísticos. El presente trabajo propone una actualización sobre HACNC, en cuanto a su fisiopatología, aspectos genéticos, clínica, metodología diagnóstica y tratamiento. Se consideran en forma particular sus posibles repercusiones sobre la fertilidad, así como el asesoramiento genético que requieren estas pacientes
Assuntos
Humanos , Feminino , Adolescente , Gravidez , Hiperplasia Suprarrenal Congênita/diagnóstico , Hiperplasia Suprarrenal Congênita/genética , Hiperplasia Suprarrenal Congênita/tratamento farmacológico , Hiperandrogenismo/etiologia , Esteroide 21-Hidroxilase/deficiência , Acetato de Ciproterona/uso terapêutico , Sulfato de Desidroepiandrosterona , Dexametasona/uso terapêutico , Fertilidade , Finasterida/uso terapêutico , Flutamida/uso terapêutico , Hirsutismo/tratamento farmacológico , Hidroxiprogesteronas , Hipertricose/diagnóstico , Infertilidade Feminina/etiologia , Distúrbios Menstruais/etiologia , Biologia Molecular , Espironolactona/uso terapêuticoRESUMO
Los síndromes de hiperandrogenismo de diferente grado constituyen un motivo de consulta frecuente en un consultorio de Ginecología Infantojuvenil. Estos cuadros suelen provocar preocupación en las adolescentes tanto por sus manifestaciones estéticas (hirsutismo, acné, alopecía) como por la presencia de alteraciones del ciclo mestrual que puede crearles dudas sobre su fertilidad futura. Una de las causas de hiperandrogenismo, la Hiperplasia Adrenal Congénita No Clásica (HACNC), cobra importancia debido a su origen genético y a que no existen elementos de la clínica que permitan diferenciarla de otras etiologías como síndrome de ovarios poliquísticos. El presente trabajo propone una actualización sobre HACNC, en cuanto a su fisiopatología, aspectos genéticos, clínica, metodología diagnóstica y tratamiento. Se consideran en forma particular sus posibles repercusiones sobre la fertilidad, así como el asesoramiento genético que requieren estas pacientes (AU)