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1.
Rev. Hosp. Ital. B. Aires (2004) ; 40(1): 34-38, mar. 2020. tab
Article in Spanish | LILACS | ID: biblio-1102292

ABSTRACT

Las mujeres han sido tratadas por décadas con testosterona intentando aliviar una gran variedad de síntomas con riesgos y beneficios inciertos. En la mayoría de los países, la testosterona se prescribe "off-label", de modo que las mujeres están utilizando compuestos y dosis ideadas para tratamientos en hombres. En este sentido, varias sociedades médicas de distintos continentes adoptaron recientemente por consenso una toma de posición sobre los beneficios y potenciales riesgos de la terapia con testosterona en la mujer, explorar las áreas de incertidumbre e identificar prácticas de prescripción con potencial de causar daño. Las recomendaciones con respecto a los beneficios y riesgos de la terapia con testosterona se basan en los resultados de ensayos clínicos controlados con placebo de al menos 12 semanas de duración. A continuación se comentan las recomendaciones. (AU)


There are currently no clear established indications for testosterone replacement therapy for women. Nonetheless, clinicians have been treating women with testosterone to alleviate a variety of symptoms for decades with uncertainty regarding its benefits and risks. In most countries, testosterone therapy is prescribed off-label, which means that women are using testosterone formulations or compounds approved for men with a modified dose for women. Due to these issues, there was a need for a global Consensus Position Statement on testosterone therapy for women based on the available evidence from placebo randomized controlled trials (RCTs). This Position Statement was developed to inform health care professionals about the benefits and potential risks of testosterone therapy intended for women. The aim of the Consensus was to provide clear guidance as to which women might benefit from testosterone therapy; to identify symptoms, signs, and certain conditions for which the evidence does not support the prescription of testosterone; to explore areas of uncertainty, and to identify any prescribing practices that have the potential to cause harm. (AU)


Subject(s)
Humans , Female , Aged , Testosterone/therapeutic use , Postmenopause/drug effects , Appetite Depressants/adverse effects , Phenytoin/adverse effects , Placebos/administration & dosage , Psychotropic Drugs/adverse effects , Tamoxifen/adverse effects , Testosterone/administration & dosage , Testosterone/analysis , Testosterone/adverse effects , Testosterone/pharmacology , Cardiovascular Agents/adverse effects , Indomethacin/adverse effects , Gonadotropin-Releasing Hormone/adverse effects , Postmenopause/physiology , Controlled Clinical Trials as Topic , Cholinergic Antagonists/adverse effects , Contraceptives, Oral/adverse effects , Sexual Dysfunctions, Psychological/etiology , Sexual Dysfunctions, Psychological/therapy , Danazol/adverse effects , Consensus , Aromatase Inhibitors/adverse effects , Off-Label Use , Factor Xa Inhibitors/adverse effects , Amphetamines/adverse effects , Histamine Antagonists/adverse effects , Androgen Antagonists/adverse effects , Androgens/physiology , Ketoconazole/adverse effects , Narcotics/adverse effects
2.
Braz. j. pharm. sci ; 52(4): 591-594, Oct.-Dec. 2016.
Article in English | LILACS | ID: biblio-951874

ABSTRACT

ABSTRACT Various studies have linked metformin, a universally antidiabetic drug, with semen quality; however, such a direct link has not been established. This review systematically addresses and summarizes the effect of metformin on semen quality, particularly sperm function. We searched the MEDLINE electronic database for English articles and abstracts containing the key words 'metformin' and 'sperm', and relevant articles were reviewed. In summary, metformin appears to have improved and provided positive impact on sperm quality. This effect may be due to the ability of metformin to reduce oxidative stress and lipid peroxidation, enhance 5'-AMP activated protein kinase activity, and restore the normal levels of pituitary-gonadal hormones. However, further clinical research is still necessary to confirm such effect.


Subject(s)
Semen/metabolism , Metformin/analysis , Metformin/adverse effects , Testosterone/pharmacology , Oxidative Stress
3.
Arq. bras. cardiol ; 107(6): 532-541, Dec. 2016. tab, graf
Article in English | LILACS | ID: biblio-838658

ABSTRACT

Abstract Background: Impaired angiogenesis in cardiac tissue is a major complication of diabetes. Protein kinase B (AKT) and extracellular signal regulated kinase (ERK) signaling pathways play important role during capillary-like network formation in angiogenesis process. Objectives: To determine the effects of testosterone and voluntary exercise on levels of vascularity, phosphorylated Akt (P- AKT) and phosphorylated ERK (P-ERK) in heart tissue of diabetic and castrated diabetic rats. Methods: Type I diabetes was induced by i.p injection of 50 mg/kg of streptozotocin in animals. After 42 days of treatment with testosterone (2mg/kg/day) or voluntary exercise alone or in combination, heart tissue samples were collected and used for histological evaluation and determination of P-AKT and P-ERK levels by ELISA method. Results: Our results showed that either testosterone or exercise increased capillarity, P-AKT, and P-ERK levels in the heart of diabetic rats. Treatment of diabetic rats with testosterone and exercise had a synergistic effect on capillarity, P-AKT, and P-ERK levels in heart. Furthermore, in the castrated diabetes group, capillarity, P-AKT, and P-ERK levels significantly decreased in the heart, whereas either testosterone treatment or exercise training reversed these effects. Also, simultaneous treatment of castrated diabetic rats with testosterone and exercise had an additive effect on P-AKT and P-ERK levels. Conclusion: Our findings suggest that testosterone and exercise alone or together can increase angiogenesis in the heart of diabetic and castrated diabetic rats. The proangiogenesis effects of testosterone and exercise are associated with the enhanced activation of AKT and ERK1/2 in heart tissue.


Resumo Fundamento: Angiogênese prejudicada em tecido cardíaco é uma das principais complicações das diabetes. As vias de sinalização da proteína-quinase B (AKT) e a quinase regulada por sinal extracelular (ERK) exercem um importante papel durante a formação de uma rede similar à capilar no processo de angiogênese. Objetivos: Determinar os efeitos da testosterona e exercícios voluntários sobre os níveis de vascularidade, AKT fosforilada (P- AKT) e ERK fosforilada (P-ERK) sobre o tecido cardíaco de ratos diabéticos e castrados diabéticos. Métodos: A diabetes tipo 1 foi induzida através de injeção intraperitoneal de 50 mg/kg de estreptozotocina em animais. Após 42 dias de tratamento com testosterona (2mg/kg/dia) ou exercícios voluntários, individualmente ou em conjunto, as amostras de tecidos cardíacos foram coletadas e usadas para avaliação histológica e determinação de níveis de P-AKT e P-ERK através do método ELISA. Resultados: Os nossos resultados mostraram que a testosterona ou os exercícios aumentaram a capilaridade, os níveis de P-AKT, e P-ERK nos corações de ratos diabéticos. O tratamento de ratos diabéticos com testosterona e exercícios obteve um efeito sinérgico sobre a capilaridade, níveis de P-AKT, e P-ERK no coração. Além disto, na capilaridade do grupo diabético castrado, os níveis de P-AKT e P-ERK diminuíram significativamente no coração, ao passo que o tratamento com testosterona ou o treinamento com exercícios reverteu tais efeitos. O tratamento simultâneo de ratos diabéticos castrados com testosterona e exercícios obteve um efeito aditivo sobre os níveis de P-AKT e P-ERK. Conclusão: Nossas descobertas sugerem que a testosterona e exercícios, em conjunto ou individualmente, podem aumentar a angiogênese nos corações de ratos diabéticos e castrados diabéticos. Os efeitos favoráveis à angiogênese da testosterona e dos exercícios estão associados à ativação reforçada de AKT e ERK1/2 no tecido cardíaco.


Subject(s)
Animals , Male , Physical Conditioning, Animal/physiology , Testosterone/pharmacology , Extracellular Signal-Regulated MAP Kinases/analysis , Diabetes Mellitus, Experimental/metabolism , Heart/drug effects , Androgens/pharmacology , Time Factors , Enzyme-Linked Immunosorbent Assay , Signal Transduction/drug effects , Reproducibility of Results , Rats, Wistar , Hormone Replacement Therapy/methods , Extracellular Signal-Regulated MAP Kinases/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Diabetes Mellitus, Experimental/physiopathology , Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 1/metabolism , Heart/physiopathology , Androgens/therapeutic use , Myocardium/chemistry
4.
Sex., salud soc. (Rio J.) ; (23): 162-186, mayo-ago. 2016.
Article in Portuguese | LILACS | ID: lil-795150

ABSTRACT

Resumo O texto tem como proposta refletir sobre os usos do hormônio testosterona entre os homens transexuais, tendo como ponto central a relação com o cuidado em saúde. O objetivo é entender, a partir do uso de fármacos a base de testosterona, como eles transversalizam, interagem e reiteram os processos de construção do que se designa transexual masculino, suas diferentes experiências e narrativas e a relação com o cuidado em saúde, seja no âmbito do serviço de referência no atendimento aos transexuais, seja nas experiências em outros serviços privados, e/ou nas vivências cotidianas experimentadas pelos homens transexuais em diferentes espaços sociais. As discussões são baseadas em seis relatos de homens transexuais na cidade do Rio de Janeiro.


Abstract This paper discusses the uses of testosterone among transsexual men and its relation to healthcare. It addresses how the use of testosterone-based drugs crisscross, interact and reiterate the processes of construction of the subjects designated as transsexual men. It analyses trans men's experiences and narratives, as well as their view of healthcare, both in trans-specific healthcare clinics and in everyday experiences in other social realms. The discussion is based on interviews with six transsexual men in the city of Rio de Janeiro.


Resumen Este artículo se propone reflexionar sobre el uso de la hormona testosterona entre hombres transexuales, teniendo como punto central la relación con el cuidado sanitario. Tiene como objetivo entender, a partir del uso de fármacos a base de testosterona, cómo éstos transversalizan, interactúan y reiteran los procesos de construcción de lo que se designa como transexual masculino, sus diversas experiencias y narrativas, así como su relación con el cuidado sanitario, sea en el ámbito del servicio específico de referencia de atención a transexuales, sea en las experiencias en otros servicios privados, y /o en las vivencias cotidianas experimentadas por hombres transexuales en diferentes espacios sociales. Las discusiones se basan en seis relatos de hombres transexuales en la ciudad de Río de Janeiro.


Subject(s)
Humans , Male , Female , Testosterone/pharmacology , Transsexualism/drug therapy , Transgender Persons , Health Services for Transgender Persons , Life Change Events , Unified Health System , Brazil , Public Health , Delivery of Health Care , Personal Narrative
5.
Rev. latinoam. enferm ; 23(2): 352-360, Feb-Apr/2015. tab, graf
Article in English | LILACS, BDENF | ID: lil-747162

ABSTRACT

OBJECTIVE: to analyze the scientific literature on home-based family care of people with severe mental illness. METHOD: integrative review of 14 databases (CINALH, Cochrane Plus, Cuidatge, CUIDEN, Eric, IBECS, EMI, ISOC, JBI COnNECT, LILACS, PsycINFO, PubMed, SciELO, and Scopus) searched with the key words "family caregivers", "severe mental illness", and "home" between 2003 and 2013. RESULTS: of 787 articles retrieved, only 85 met the inclusion criteria. The articles appeared in 61 journals from different areas and disciplines, mainly from nursing (36%). The countries producing the most scientific literature on nursing were Brazil, the UK, and the US, and authorship predominantly belonged to university centers. A total of 54.12% of the studies presented quantitative designs, with descriptive ones standing out. Work overload, subjective perspectives, and resources were the main topics of these papers. CONCLUSIONS: the international scientific literature on home-based, informal family care of people with severe mental disorder is limited. Nursing research stands out in this field. The prevalent topics coincide with the evolution of the mental health system. The expansion of the scientific approach to family care is promoted to create evidence-based guidelines for family caregivers and for the clinical practice of professional caregivers. .


OBJETIVO: analisar a produção científica sobre o cuidado familiar de pessoas com transtorno mental grave em casa. MÉTODO: revisão integrativa de 14 bases de dados (CINALH, Cochrane Plus, Cuidatge, CUIDEN, Eric, IBECS, EMI, ISOC, JBI Connect, LILACS, PsycInfo e PubMed, SciELO, e Scopus), com as palavras-chave "cuidadores familiares", "TMG" (transtornos mentais graves ) e "casa", realizada entre 2003 e 2013. RESULTADOS: dos 787 artigos retornados, somente 85 atenderam os critérios de inclusão. Os artigos vieram de 61 periódicos de diferentes áreas e disciplinas, principalmente de enfermagem (36%). Os países com maior produção científica sobre enfermagem foram o Brasil, o Reino Unido e os Estados Unidos, e a autoria era predominantemente de centros universitários. Um total de 54,12% dos estudos apresentou delineamento quantitativo, e os descritivos se destacaram. Os principais temas desses trabalhos foram sobrecarga de trabalho, perspectivas subjetivas e recursos. CONCLUSÕES: a produção cientifica internacional sobre o cuidado familiar informal de pessoas com doenças mentais graves em casa é limitada. A pesquisa em enfermagem se destaca nesse campo. Os temas prevalentes coincidem com a evolução do sistema de saúde mental. Estimula-se a expansão da abordagem científica do cuidado familiar de modo a encontrar evidências para criar guias para cuidadores familiares e para a prática clínica de cuidadores profissionais. .


OBJETIVO: analizar la producción científica sobre el cuidado familiar de la persona con trastorno mental grave en el hogar familiar. MÉTODO: revisión integradora en 14 bases de datos (CINALH, Cochrane Plus, Cuidatge, CUIDEN, Eric, IBECS, IME, ISOC, JBI ConNECT, LILACS, PsycInfo, PubMed, SciELO y Scopus), con las palabras clave "cuidadores familiares", "TMG" y "hogar"; realizada entre 2003 y 2013. RESULTADOS: de 787 artículos recuperados, sólo 85 cumplieron con los criterios de inclusión. Los artículos procedieron de 61 revistas de diferentes áreas y disciplinas destacando la disciplina de enfermería (36%). Los países con mayor producción científica sobre enfermería fueron Brasil, Reino Unido y EEUU. En la autoría predominaron los centros universitarios. El 54,12% de los estudios presentó diseño cuantitativo, sobresaliendo los descriptivos. Las temáticas destacadas fueron sobrecarga, perspectivas subjetivas y recursos. CONCLUSIONES: la producción científica internacional sobre el cuidado informal familiar de la persona con trastorno mental grave, en el contexto del hogar familiar, es limitada. En este campo, destaca la investigación de enfermería. Las temáticas prevalentes coinciden con la evolución del sistema de salud mental. Se estimula la ampliación del abordaje científico del cuidado familiar con el fin de encontrar evidencias para la elaboración de guías de cuidadores familiares y para la práctica clínica de cuidadores profesionales. .


Subject(s)
Humans , Female , Adipogenesis , Adipocytes/metabolism , Adult Stem Cells/physiology , Androgens/physiology , Dihydrotestosterone/pharmacology , Testosterone/physiology , Androgen Antagonists/pharmacology , Androgens/pharmacology , /metabolism , CCAAT-Enhancer-Binding Protein-beta/genetics , CCAAT-Enhancer-Binding Protein-beta/metabolism , CCAAT-Enhancer-Binding Proteins/genetics , CCAAT-Enhancer-Binding Proteins/metabolism , Cells, Cultured , Flutamide/pharmacology , Gene Expression , Lipid Metabolism , PPAR gamma/genetics , PPAR gamma/metabolism , Receptors, Androgen/metabolism , Signal Transduction , Testosterone/pharmacology
6.
IBJ-Iranian Biomedical Journal. 2013; 17 (4): 221-224
in English | IMEMR | ID: emr-148461

ABSTRACT

The secretion of thyroxin [T4] as the main hormone of thyroid gland is regulated by androgens. The present study aimed to evaluate the effect of testosterone and finasteride administration and castration on serum levels of T4 and to show the effect of this regulation on total body weight, weight of testis, and the weight of prostate. Male adult rats [n = 32] were divided into 4 groups [n = 8]: Group 1 [control], Group 2 [castration], Group 3 [finasteride: 20 mg/kg/day] and Group 4 [testosterone: 5 mg/kg/day]. At the end of the study [35 days], serum level of thyroxin, body weight, weight of testis, and prostate were determined. The data showed that the body weight increased in castrated [P = 0.04] and decreased in testosterone [P = 0.00] groups but did not differ in finasteride [P>0.05] group. There were not any differences in the weight of testis among control, finasteride, and testosterone groups but the weight of prostate increased in testosterone group [P = 0.00] and decreased in castrated [P = 0.03] and finasteride groups [P = 0.04]. In addition, the serum level of T4 [nmo/ml] decreased in the three groups: finasteride [P = 0.03], testosterone [P = 0.04], and castrated [P = 0.00]. Testosterone in both high and low levels decreased the amount of T4 with a time-dependent manner


Subject(s)
Animals, Laboratory , Testosterone/pharmacology , Castration , Finasteride/pharmacology , Rats, Wistar
7.
Braz. j. med. biol. res ; 44(11): 1118-1124, Nov. 2011. ilus
Article in English | LILACS | ID: lil-604270

ABSTRACT

The testicular feminized (Tfm) mouse carries a nonfunctional androgen receptor (AR) and reduced circulating testosterone levels. We used Tfm and castrated mice to determine whether testosterone modulates markers of aging in cardiomyocytes via its classic AR-dependent pathway or conversion to estradiol. Male littermates and Tfm mice were divided into 6 experimental groups. Castrated littermates (group 1) and sham-operated Tfm mice (group 2, N = 8 each) received testosterone. Sham-operated Tfm mice received testosterone in combination with the aromatase inhibitor anastrazole (group 3, N = 7). Castrated littermates (group 4) and sham-operated untreated Tfm mice (group 5) were used as controls (N = 8 and 7, respectively). An additional control group (group 6) consisted of age-matched non-castrated littermates (N = 8). Cardiomyocytes were isolated from the left ventricle, telomere length was measured by quantitative PCR and expression of p16INK4α, retinoblastoma (Rb) and p53 proteins was detected by Western blot 3 months after treatment. Compared with group 6, telomere length was short (P < 0.01) and expression of p16INK4α, Rb and p53 proteins was significantly (P < 0.05) up-regulated in groups 4 and 5. These changes were improved to nearly normal levels in groups 1 and 2 (telomere length = 0.78 ± 0.05 and 0.80 ± 0.08; p16INK4α = 0.13 ± 0.03 and 0.15 ± 0.04; Rb = 0.45 ± 0.05 and 0.39 ± 0.06; p53 = 0.16 ± 0.04 and 0.13 ± 0.03), but did not differ between these two groups. These improvements were partly inhibited in group 3 compared with group 2 (telomere length = 0.65 ± 0.08 vs 0.80 ± 0.08, P = 0.021; p16INK4α = 0.28 ± 0.05 vs 0.15 ± 0.04, P = 0.047; Rb = 0.60 ± 0.06 vs 0.39 ± 0.06, P < 0.01; p53 = 0.34 ± 0.06 vs 0.13 ± 0.03, P = 0.004). In conclusion, testosterone deficiency contributes to cardiomyocyte aging. Physiological testosterone can delay cardiomyocyte aging via an AR-independent pathway and in part by conversion to estradiol.


Subject(s)
Animals , Male , Mice , Aging/metabolism , Cellular Senescence/physiology , Estradiol/metabolism , Myocytes, Cardiac/physiology , Receptors, Androgen/metabolism , Testosterone/pharmacology , Aging/pathology , Biomarkers/analysis , /drug effects , Models, Animal , Orchiectomy , Random Allocation , Retinoblastoma Protein/metabolism , Telomere Shortening/drug effects , Testosterone/deficiency , /metabolism
8.
Braz. j. pharm. sci ; 46(1): 79-89, Jan.-Mar. 2010. graf, tab
Article in English | LILACS | ID: lil-548738

ABSTRACT

The aim of the work was evaluate the effects of testosterone undecanoate (TU) treatment combined with moderate physical training on: the estrous cycle, body weight (BW), motor behavior (MB), and the morphohistology of the reproductive system, the liver and kidney in rats. Female Wistar rats (180 g - 250 g) were divided as follows: sedentary + TU (S + TU), trained + TU (T + TU), sedentary + vehicle (S + V), trained + vehicle (T + V). The rats swam 50 min/Day, strapped with a 5 percent BW load, for 4 weeks. During this training, (BW) was monitored daily as well as the estrous cycle (EC) by vaginal smear. The TU (15 mg/kg s.c) was administered 3 times/week for 4 weeks. At the end of the study, data on MB, BW and morphohistopathological changes in viscera were compiled. The (T + TU) group had on average, a higher (BW) in the fourth week compared to the first week, and (BW) higher than (S + V) and (S + TU) groups. We noted an interruption in the EC and a decrease in weight of ovaries in animals treated with TU. In addition, there was an increase in the relative weight of the heart in groups (T + V) and (T+ TU), and kidneys in group (T + TU). Histopathological analysis showed periportal congestion and isolated foci of hepatic necrosis in rats with TU. Thus, TU combined with training abolished the EC, promoted ovarian atrophy, liver necrosis, cardiac hypertrophy and a decrease in motor activity.


O objetivo do trabalho foi avaliar o efeito do tratamento com undecanoato de testosterona (UT) combinado ao treinamento físico moderado sobre ciclo estral, peso corporal, estruturas do sistema reprodutor, comportamento motor e morfologia hepática e renal em ratas. Ratas Wistar (180 a 250 g) foram divididas em: sedentárias + UT (S+UT), treinadas + UT (T+UT), sedentárias + veículo (S+V), treinadas + veículo (T+V). As ratas nadaram 50 min/dia com sobrecarga de ~5 por cento do peso corporal por 4 semanas. Durante o período de treinamento foi realizado acompanhamento diário do peso corporal (PC) e do ciclo estral (CE) pelo esfregaço vaginal. O UT (15 mg/kg s.c.) foi administrado 3x/semana durante 4 semanas. Ao final foram avaliados comportamento motor, pesos e alterações histopatológicas de alguns órgãos. O grupo T+UT apresentou PC maior na quarta semana do que na primeira, com pesos corporais maiores que os grupos S+V e S+UT. Houve interrupção no CE e redução do peso dos ovários nos animais tratados com UT. Houve aumento do peso relativo do coração, nos grupos T+V e T+UT, e do peso relativo dos rins, no grupo T+UT. A análise histopatológica revelou congestão periportal e focos isolados de necrose hepática nas ratas com UT. O UT combinado com treinamento produziu supressão do ciclo estral, atrofia ovariana, necrose hepática, hipertrofia cardíaca e redução da atividade motora.


Subject(s)
Female , Adult , Rats , Animals , Estrous Cycle/drug effects , Exercise/physiology , Kidney/drug effects , Liver/drug effects , Motor Activity/drug effects , Testosterone/pharmacology , Analysis of Variance
9.
Rev. bras. ginecol. obstet ; 31(9): 453-460, set. 2009. ilus, tab
Article in Portuguese | LILACS | ID: lil-529613

ABSTRACT

OBJETIVO: avaliar os efeitos da administração de dois esteroides sintéticos sobre a morfologia do útero e parâmetros reprodutivos de ratas adultas. MÉTODOS: quarenta ratas foram aleatoriamente distribuídas nos grupos experimentais: controle (C; solução fisiológica); tratados com decanoato de nandrolona (DN; 7,5 mg/kg de peso corpóreo); composto de ésteres de testosterona (T; 7,5 mg/kg de peso corpóreo); e, simultaneamente, com DN e T (7,5 mg/kg de peso corpóreo de cada esteroide), em uma única dose/semana, intraperitoneal, durante oito semanas. Cinco fêmeas de cada grupo foram sacrificadas e os cornos uterinos foram coletados, pesados e preparados para avaliação histológica e morfométrica. As ratas restantes foram acasaladas com machos normais para avaliação dos parâmetros reprodutivos, constituindo os grupos tratados durante o período pré-gestacional. Outro grupo de 20 ratas recebeu os tratamentos durante o período gestacional (7º-14º dias). Foi aplicada a análise de variância não paramétrica de Kruskal-Wallis, complementada com o teste de Dunn ou de Student-Newman-Kleus para análise dos dados (5 por cento de significância). RESULTADOS: houve aumento significativo no peso corpóreo das fêmeas androgenizadas (DN: 305±50; T: 280±35; DN+T: 275±30 versus C: 255±22 g) (p<0,05). O peso uterino não foi afetado pelos tratamentos esteroidais (DN: 0,6±0,2; T: 0,4±0,04; DN+T: 0,7±0,1 versus C: 0,4±0,09 g). Todas as fêmeas androgenizadas apresentaram aciclicidade estral e endométrio caracterizado pelo revestimento luminal papilífero, estroma edematoso com áreas hemorrágicas e atividade secretora. Houve alterações nos parâmetros morfométricos de espessura do epitélio luminal, miométrio e perimétrio, em função do grupo androgenizado. Nenhuma rata exibiu prenhez quando tratada com os esteroides no período pré-gestacional, e o tratamento durante a organogênese afetou negativamente os parâmetros reprodutivos. CONCLUSÕES: os agentes esteroidais alteram ...


PURPOSE: to evaluate the effects of the administration of two synthetic steroids in the uterus morphology and in the reproductive parameters of adult female rats. METHODS: divided into four experimental groups: control (C; physiological solution); treated with nandrolone decanoate (DN; 7.5 mg/kg of body weight); with a testosterone esters compound (T; 7.5 mg/kg); and simultaneously with DN and T (7.5 mg/kg of each steroid), in a single intraperitoneal weekly dose, for eight weeks. Five females of each group were sacrificed and the uterine horns were collected, weighted and prepared for histological and morphometrical evaluation. The remaining rats were mated with normal male rats for reproductive parameters evaluation, composing the groups treated during the pre-gestational period. Another group of 20 female rats were treated during the gestational period (7th-14th days). For data analysis, the Kruskal-Wallis non-parametric variance analysis was used, followed by the test of Dunn or of Student-Newman-Keus (5 percent significance level). RESULTS: there was a significant body weight increase in the androgenized females (ND: 305±50; T: 280±35; ND+T: 275±30 versus C: 255±22 g; p<0.05). Uterine weight was not affected by the steroidal treatment (ND: 0.6±0.2; T: 0.4±0.04; ND+T: 0.7±0.1 versus C: 0.4±0.09 g). All the androgenized females presented estral acyclicity and endometrium characterized by papilliferous luminal lining, oedematous stroma with hemorrhagic areas and secretory activity. There were changes in the morphometrical thickness parameters of the luminal epithelium, myometrium and perimetrium in the androgenized groups. None of the female rats got pregnant when treated with steroids in the pre-gestational period and the treatment during organogenesis affected negatively the reproductive parameters. CONCLUSIONS: steroidal agents alter the uterine structure and impair fertility and gestational outcome in female rats.


Subject(s)
Animals , Female , Rats , Anabolic Agents/pharmacology , Nandrolone/analogs & derivatives , Reproduction/drug effects , Testosterone/analogs & derivatives , Testosterone/pharmacology , Uterus/drug effects , Age Factors , Nandrolone/pharmacology , Uterus/pathology
10.
Indian J Exp Biol ; 2007 Aug; 45(8): 676-82
Article in English | IMSEAR | ID: sea-56708

ABSTRACT

In vitro effects of gonadal hormones (testosterone, 17beta-estradiol estriol and estrone) and corticosteroid hormones (corticosterone and cortisol) were studied on arylalklyamine N-acetyltransferase (AA-NAT) activity in the pineal organ of the fish, C. gariepinus during quiescent, progressive, breeding and regressive phases of its annual breeding cycle. The pineals were collected under dim red light, maintained in organ culture for 7 hr and incubated with three concentrations (10(-6), 10(-5) and 10(-4) M) of hormones for 6 hr. The treatments with gonadal hormones and corticosteroid hormones inhibited pineal AA-NAT activity in a dose-dependent manner during all the phases of the breeding cycle. AA-NAT activity was comparatively more sensitive to the inhibitory effects of the gonadal hormones during the regressive phase and less sensitive during the quiescent phase. Further, the enzyme activity was more sensitive to the inhibitory effects of corticosteroid hormones (corticosterone and cortisol) during the breeding phase and less sensitive during the quiescent phase. These findings seem to suggest that gonadal hormones and corticosteroid hormones have direct inhibitory influence on AA-NAT activity and, hence melatonin synthesis in the photoreceptive pineal organ of C. gariepinus.


Subject(s)
Adrenal Cortex Hormones/pharmacology , Animals , Arylamine N-Acetyltransferase/antagonists & inhibitors , Breeding , Catfishes/growth & development , Estradiol/pharmacology , Estriol/pharmacology , Gonadal Steroid Hormones/pharmacology , Melatonin/metabolism , Pineal Gland/drug effects , Testosterone/pharmacology
11.
Biol. Res ; 40(3): 329-338, 2007. graf
Article in English | LILACS | ID: lil-481310

ABSTRACT

Although evidence is accumulating that prenatal testosterone (T) compromises reproductive function in the female, the effects of excess T in utero on the postnatal development of male reproductive function has not been studied. The aim of this study was to assess the influence of prenatal T excess on age-related changes in pituitary and gonadal responsiveness to GnRH in the male sheep. We used the GnRH agonist, leuprolide (10 µg/kg), as a pharmacologic challenge at 5, 10, 20 and 30 weeks of age. These time points correspond to early and late juvenile periods and the prepubertal and postpubertal periods of sexual development, respectively. LH and T were measured in blood samples collected before and after GnRH agonist administration. The area under the response curve (AUC) of LH increased progressively in both controls and prenatal T-treated males from 5 to 20 weeks of age (P<0.01). The LH responses in prenatal T-treated males were lower at 20 and 30 weeks of age compared to controls (P<0.05). AUC-T increased progressively in control males from 5 through 30 weeks of age and prenatal T-treated males from 5 to 20 weeks of age. The T response in prenatal T-treated males was higher at 20 weeks compared to controls of same age but similar to controls and prenatal T-treated males at 30 weeks of age (P <0.05). Our findings suggest that prenatal T treatment advances the developmental trajectory of gonadal responsiveness to GnRH in male offspring.


Subject(s)
Animals , Female , Male , Pregnancy , Gonadotropin-Releasing Hormone/agonists , Gonads/drug effects , Leuprolide/pharmacology , Luteinizing Hormone/drug effects , Prenatal Exposure Delayed Effects , Testosterone/pharmacology , Area Under Curve , Luteinizing Hormone/blood , Sheep , Time Factors , Testosterone/blood
12.
Article in English | WPRIM | ID: wpr-200810

ABSTRACT

Phospholipid hydroperoxide glutathione peroxidase(PHGPx), an antioxidative selenoprotein, is modulated byestrogen in the testis and oviduct. To examine whetherpotential endocrine disrupting chemicals (EDCs) affectthe microenvironment of the testes, the expression patternsof PHGPx mRNA and histological changes were analyzedin 5-week-old Sprague-Dawley male rats exposed to severalEDCs such as an androgenic compound [testosterone (50,200, and 1,000microg/kg)], anti-androgenic compounds [flutamide(1, 5, and 25mg/kg), ketoconazole (0.2 and 1mg/kg), anddiethylhexyl phthalate (10, 50, and 250mg/kg)], andestrogenic compounds [nonylphenol (10, 50, 100, and 250mg/kg), octylphenol (10, 50, and 250mg/kg), and diethyl-stilbestrol (10, 20, and 40microg/kg)] daily for 3 weeks via oraladministration. Mild proliferation of germ cells andhyperplasia of interstitial cells were observed in the testesof the flutamide-treated group and deletion of thegerminal epithelium and sloughing of germ cells wereobserved in testes of the diethylstilbestrol-treated group.Treatment with testosterone was shown to slightly decreasePHGPx mRNA levels in testes by the reverse transcription-polymerase chain reaction. However, anti-androgeniccompounds (flutamide, ketoconazole, and diethylhexylphthalate) and estrogenic compounds (nonylphenol,octylphenol, and diethylstilbestrol) significantly up-regulated PHGPx mRNA in the testes (p<0.05). Thesefindings indicate that the EDCs might have a detrimentaleffect on spermatogenesis via abnormal enhancement ofPHGPx expression in testes and that PHGPx is useful as abiomarker for toxicity screening of estrogenic or anti-androgenic EDCs in testes.


Subject(s)
Androgen Antagonists/pharmacology , Animals , Diethylhexyl Phthalate/pharmacology , Diethylstilbestrol/pharmacology , Endocrine Disruptors/pharmacology , Estrogens, Non-Steroidal/pharmacology , Flutamide/pharmacology , Glutathione Peroxidase/biosynthesis , Histocytochemistry , Ketoconazole/pharmacology , Male , Phenols/pharmacology , RNA, Messenger/biosynthesis , Rats , Rats, Sprague-Dawley , Reverse Transcriptase Polymerase Chain Reaction , Spermatogenesis/drug effects , Testis/drug effects , Testosterone/pharmacology
13.
Braz. j. morphol. sci ; 23(2): 247-253, Apr.-June 2006. ilus, tab
Article in English | LILACS | ID: lil-468064

ABSTRACT

The effects of testosterone on skeletal muscle were assessed in adult male Wistar rats aged 80 days and 1 year. The animals were divided into 4 groups: young testosterone (YT), old testosterone (OT), young control (YC), and old control (OC) groups. The YT and OT groups received 15 applications of testosterone cypionate (5 mg/kg) on alternate days and the controls received injections containing sterile oil alone. After 30 days the animals were sacrificed and the soleus (SOL) and extensor digitorum longus (EDL) muscles were analyzed using mATPase histochemistry. After treatment, YT group gained less body weight than YC group and OT group decreased body weight, differently from the body weight gain observed in the OC group. Testosterone treatment did not show significant changes in both relative muscle weight and muscle fiber composition profile. However, in the YT group we observed an increase in the cross-sectional area of type I fibers in the SOL muscle, and type I and IIAD fibers in the EDL muscle. In the OT group, the cross sectional area of type I was decreased in the EDL muscle. These results reveal that testosterone did not cause a shift in muscle fiber type, but the cross-sectional area had fiber type-specific changes.


Subject(s)
Animals , Male , Adult , Rats , Muscle Fibers, Fast-Twitch , Muscle Fibers, Skeletal , Muscle, Skeletal , Muscle, Skeletal/cytology , Muscle, Skeletal/metabolism , Testosterone , Testosterone/metabolism , Histocytochemistry , Rats, Wistar , Testosterone/pharmacology
14.
Gac. méd. Méx ; 142(1): 1-8, ene.-feb. 2006. ilus
Article in Spanish | LILACS | ID: lil-571159

ABSTRACT

Utilizando segmentos de aorta de rata sin endotelio inmersos en solución sin Ca2+, evaluamos la capacidad de la testosterona para modificar el efecto contráctil del agonista adrenérgico fenilefrina, así como el incremento en el tono de reposo (ITR) asociado con la entrada capacitativa de calcio por el sarcoplasma. La testosterona [10-5–10- 4 M] inhibió significativamente la contracción activada por la fenilefrina [10-6 M] y el ITR. Estos efectos no fueron modificados con cicloheximida [10-5 M] (inhibidor de la síntesis protéica), flutamida [10-5 M] (antagonista de receptores androgénicos), o aminoglutetimida [10-5 M] (inhibidor de la citocromo P450 aromatasa). La testosterona también inhibió las respuestas contráctiles de la serotonina [10-5 M], pero no de la cafeína [10-2 M]. Además, la testosterona inhibió las contracciones del ácido ciclopiazónico [10-6 M] y de la ryanodina [10- 5 M] asociadas con el ingreso capacitativo de Ca2+ mediante canales de Ca2+ tipo no L. Estos datos sugieren que la testosterona interfiere con la vía de transducción de los receptores acoplados a proteínas Gq- 11, e inhibe la entrada capacitativa de Ca2+ a través de canales de Ca2+ tipo L y tipo no L; los efectos son no genómicos, independientes de receptores androgénicos, y de la conversión testosterona en estrógenos.


Using endothelium-denuded rat aortic rings incubated in Ca2+ -free solution, we assessed the ability of testosterone to influence the contractile effect of phenylephrine, and the increase in resting tone (IRT) associated with Ca2+ ability to cross the plasma membrane. The addition of testosterone [10(-5)-10(-4) 5 min before phenylephrine [10(-6) M], inhibited both phenylephrine-induced contraction and IRT. These changes were not affected by cycloheximide (10(-5) M; a protein synthesis inhibitor of), flutamide (10(-5) M; an androgenic receptor antagonist), or by adding aminoglutethimide (10(-5) M; an aromatase inhibitor). Testosterone also blocked the contractile response to serotonin [10(-5) M] but not to caffeine [10(-2) M]. On the other hand, testosterone inhibited the contractile responses to cyclopiazonic acid (10(-6) M; a selective Ca2+ -ATPase inhibitor) or ryanodine (10(-5 M; an activator of sarcoplasmic reticulum Ca2+ -release channels) associated with capacitative Ca2+ influx through non-L-type Ca2+ channels. These data suggest that by acting on the cellular membrane, testosterone interferes with the signal transduction pathway of G(q-11) protein-coupled receptors, and inhibits capacitative Ca2+ influx through both L-type and non-L-type Ca2+ channels. These effects are non-genomic, non-mediated by the intracellular androgen receptor, and not due to the conversion of testosterone to estrogens.


Subject(s)
Animals , Male , Rats , Aorta/drug effects , Aorta/physiology , Calcium/metabolism , Cells/metabolism , Phenylephrine/pharmacology , Testosterone/pharmacology , Vasoconstrictor Agents/pharmacology , Vasodilation/drug effects , Muscle Contraction , Rats, Wistar
15.
Indian J Exp Biol ; 2005 Nov; 43(11): 1080-7
Article in English | IMSEAR | ID: sea-57076

ABSTRACT

Germ cell death and their removal from the seminiferous epithelium are common in the affected testis in conditions of unilateral ischemia or cryptorchidism; the similarities and differences, however, have not been studied between these two conditions. The present study was designed to examine the severity of the effect on testicular germ cells during the initial stages of both ischemia and cryptorchidism, which have significant implications on the restoration of fertility following surgical repair. Complete absence of spermatids was observed following 12 hr of ischemia as compared to 7 days of cryptorchidism. Germ cell removal in either case was in the direction of lumen to basement membrane leaving only a single layer of cells by 24 hr of unilateral ischemia as compared to 15 days of cryptorchidism. Levels of intratesticular testosterone was found lower in cryptorchidism (7 days) but not in ischemia till 24 hrs. Giant cells frequently observed in cryptorchid testis were absent in the ischemic seminiferous epithelium. There was a gradual increase in the number of apoptotic and non-viable cells; the latter was more than 95% by 24 hr of ischemia. In contrast, approximately 85% testicular cells were nonviable till 15 days of cryptorchidism. The 1c peak representing the population of haploid cells was significantly reduced in cryptorchidism (7 days), while the peak was completely abolished by 24 hr of ischemia. Rise in the levels of oxidative stress in the affected testis was observed identically during the initial stages. These findings indicate that coupled with the rise in tissue oxidative stress, the number of apoptotic/nonviable germ cells was alarmingly high (> 80%) by 15 days of cryptochidism or 24 hr of ischemia. Restoration of complete spermatogenesis following surgical repair may not be possible in such cases because of these acute adverse effects.


Subject(s)
Animals , Apoptosis , Cell Survival , Cryptorchidism/pathology , DNA/chemistry , Flow Cytometry , Germ Cells/pathology , Haploidy , Hormones/metabolism , In Situ Nick-End Labeling , Ischemia/pathology , Lipid Peroxidation , Male , Oxidative Stress , Rats , Seminiferous Epithelium/pathology , Testicular Diseases/pathology , Testis/pathology , Testosterone/pharmacology , Time Factors
16.
Braz. j. med. biol. res ; 38(4): 553-558, Apr. 2005. ilus, graf
Article in English | LILACS | ID: lil-398173

ABSTRACT

Increased levels of androgens in postmenopausal women are considered to be a risk factor for breast cancer. Testosterone, alone or in combination with estrogen, induces epithelial dysplasia and mammary tumors in Noble rats. Since this model of hormone-induced neoplasia has not been reported in other rat strains, we studied the effect of testosterone on the mammary gland morphology of female Wistar rats. Sixty adult, non-castrated, female Wistar rats were implanted in the dorsum midline with a silicone tube containing 50 mg testosterone (testosterone propionate in 30 animals and non-esterified testosterone in the remaining 30 animals) and 20 additional animals were implanted with empty tubes and used as control. Five animals per group were killed 30, 60, 90, 120, 150, and 180 days after implantation, and the mammary glands were dissected, fixed and embedded in paraffin. Histological sections were then stained with hematoxylin and eosin and picrosyrius red for collagen visualization. Morphological and morphometric analysis demonstrated ductal proliferation and acinotubular differentiation with secretory activity in all treated animals, peaking at 90 days of androgen exposure. After 90 days the proliferation of acinar epithelial cells was evident, but there was a progressive reduction of secretory differentiation and an increase in intralobular collagen fibers. There was no morphological evidence of dysplastic changes or other pre-neoplastic lesions. Testosterone treatment applied to adult, non-castrated female Wistar rats induced a mammary gland hyperplasia resembling the lactating differentiation, with progressive reduction in secretory differentiation.


Subject(s)
Animals , Female , Rats , Androgens/pharmacology , Mammary Glands, Animal/drug effects , Testosterone/pharmacology , Carcinogenicity Tests , Hyperplasia/chemically induced , Mammary Glands, Animal/pathology , Mammary Glands, Animal , Rats, Wistar , Time Factors
17.
Article in English | WPRIM | ID: wpr-53835

ABSTRACT

Androgens remain a common treatment for certain type of anemia, based upon its myelostimulating effects; however, it has not been established whether androgens affect apoptosis of hematopoietic progenitor cells (HPCs). We investigated the effects of the androgens, such as testosterone, 5beta-dihydrotestosterone (5-DHT), and oxymetholone, on apoptosis of normal hematopoietic progenitor cells in vitro. Androgens did not rescue normal bone marrow (BM) CD34+ cells and colony-forming cells (CFCs), other than mature erythroid CFCs, from apoptosis induced by serum- and growth factor deprivation. Oxymetholone did not affect growth factor-mediated survival of normal CD34+ cells or its inhibition by interferon-gamma (IFN-gamma). In a standard methylcellulose clonogenic assay, low concentrations of oxymetholone and 5-DHT stimulated the clonal growth of colony-forming unit (CFU)-erythroid, but did not affect growth of CFU-granulocyte/macrophage or burst-forming unit-erythroid. Oxymetholone and 5-DHT stimulated the production of stem cell factor in normal bone marrow stromal cells (BMSCs) via transcriptional regulation. In agreement with this, oxymetholone-treated BMSCs better supported the survival of HPCs. These data indicate that survival-enhancing or growth-stimulatory effects of androgens on hematopoietic progenitor cells are minimal and mostly restricted to mature erythroid progenitors, and its myelostimulating effects could be attributed, at least in part, to the stimulation of production of hematopoietic growth factors in BMSCs.


Subject(s)
Androgens/pharmacology , Antigens, CD34/analysis , Apoptosis/drug effects , Blotting, Northern , Blotting, Western , Bone Marrow Cells/cytology , Cell Survival/drug effects , Cells, Cultured , Chemokines, CXC/genetics , Colony-Forming Units Assay , Cytokines/genetics , Dihydrotestosterone/pharmacology , Dose-Response Relationship, Drug , Flow Cytometry , Gene Expression/drug effects , Hematopoietic Stem Cells/cytology , Humans , Oxymetholone/pharmacology , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , Testosterone/pharmacology , Time Factors
18.
Indian J Exp Biol ; 2004 Mar; 42(3): 283-7
Article in English | IMSEAR | ID: sea-57536

ABSTRACT

The effects of administration of cortisol, corticosterone, testosterone, progesterone and a synthetic estrogen. diethylstilbestrol (DES) on total brain Na(+)-K+- ATPase were investigated in tilapia, O. mossambicus. Exogenous administration of 0.125 and 0.25 microg/g body weight of glucocorticoids and 0.125, 0.25 and 0.5 microg/g body weight of DES for 5 days significantly stimulated Na+(-) K+ ATPase activity by 14-41% in the brain, while 0.5 microg/g body weight of glucocorticoids did not evoke any response on the activity of the enzyme. Progesterone (0.125 and 0.25 microg/g body weight) administration significantly decreased the enzyme activity by 21-36% and high dose (0.5 microg/g body weight) was ineffective. Testosterone exhibited a biphasic effect on Na(+)-K+ ATPase activity--a low dose stimulated by 14% while middle and high doses inhibited it by 19-24%. The results seem to be the first report on the effect of steroids on brain ATPase activity in a teleost. When 0.25microg/g body weight of actinomycin D or puromycin was administered prior to the treatment of similar doses of hormones, the inhibitors significantly inhibited the effect of the hormones by 24-52%. This clearly shows that the effect of the hormones was sensitive to the action of inhibitors suggesting a possible genomic mode of action under long-term treatment. The results suggest that cortisol, corticosterone and DES may possibly stimulate the co-transport of glucose and excitation of membrane potential while progesterone and testosterone inhibit them in the brain of O. mossambicus by regulating the activity of Na(+)-K+ ATPase.


Subject(s)
Animals , Body Weight , Brain/drug effects , Corticosterone/pharmacology , Dactinomycin/pharmacology , Diethylstilbestrol/pharmacology , Dose-Response Relationship, Drug , Fishes , Hydrocortisone/pharmacology , Progesterone/pharmacology , Puromycin/pharmacology , Sodium-Potassium-Exchanging ATPase/metabolism , Steroids/pharmacology , Testosterone/pharmacology , Tilapia
19.
Rev. Hosp. Clin. Fac. Med. Univ. Säo Paulo ; 59(1): 32-38, Jan. 2004. tab
Article in English | LILACS | ID: lil-356987

ABSTRACT

O uso da testosterona em homens idosos, conhecido como Terapia de Reposição Hormonal no homem ou Terapia de Reposição com Androgênios, têm aumentado o interesse para as comunidades médica e leiga na última década. Muito embora o conhecimento a respeito dos potenciais benefícios e riscos da Terapia de Reposição Hormonal nos homens tem aumentado dramaticamente, ainda existe muito que precisa ser determinado. Embora existam vários benefícios potenciais da Terapia de Reposição com Androgênios e dados clínicos relacionados com o uso de tal terapia, não existem ainda nenhum estudo controlado, randomizado e multicêntrico avaliando o uso de tal terapia. O objetivo deste artigo é revisar os aspectos atuais sobre os possíveis riscos e benefícios da Terapia de Reposição com Androgênios discutindo os estudos clínicos publicados sobre o assunto.


Subject(s)
Humans , Male , Aged , Androgens/therapeutic use , Hormone Replacement Therapy , Testosterone/therapeutic use , Androgens/pharmacology , Hormone Replacement Therapy/adverse effects , Risk Assessment , Treatment Outcome , Testosterone/pharmacology
20.
Biol. Res ; 37(4): 625-633, 2004. tab, graf
Article in English | LILACS | ID: lil-437518

ABSTRACT

We studied the effect of IGF-I, insulin and testosterone on intracellular Ca2+ in cultured muscle cells. Insulin produced a fast (<1 s) and transient [Ca2+] increase lasting less than 10 s. IGF-I induced a transient [Ca2+] increase, reaching a fluorescence peak 6 s after stimulus, to return to basal values after 60 s. Testosterone induced delayed (35 s) and long lasting (100-200 s) signals, frequently associated with oscillations. IGF-I, testosterone and electrical stimulation-induced Ca2+ signals were shown to be dependent on IP3 production. All of these Ca2+ signals were blocked by inhibitors of the IP3 pathway. On the other hand, insulin-induced Ca2+ increase was dependent on ryanodine receptors and blocked by either nifedipine or ryanodine. The different intracellular Ca2+ patterns produced by electrical stimulation, testosterone, IGF-I and insulin, may help to understand the role of intracellular calcium kinetics in the regulation of gene expression by various stimuli in skeletal muscle cells.


Subject(s)
Animals , Rats , Muscle Cells , Muscle Cells/metabolism , Insulin-Like Growth Factor I/pharmacology , Insulin/pharmacology , Calcium Signaling , Calcium Signaling/physiology , Testosterone/pharmacology , Cell Culture Techniques , Calcium/metabolism , Electric Stimulation , Gene Expression , Transcription Factors/metabolism , Myocytes, Cardiac , Myocytes, Cardiac/metabolism , Muscle, Skeletal/cytology , Muscle, Skeletal , Membrane Potentials
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