The effect of androgen on wool follicles and keratin production in Hetian sheep / Efeito do androgênio na produção de folículos e queratina em ovinos Hetianos

Abstract To investigate the optimal androgen concentration for culturing Hetian sheep wool follicle and to detect effects of androgen concentration on wool follicle cell proliferation and apoptosis using immunofluorescence labeling and real-time quantitative fluorescence determinations of wool keratin-associated protein gene expression levels. Wool follicles were isolated by microdissection and wool follicles and skin pieces were cultured in various concentrations of dihydrotestosterone (DHT) in culture medium. Next, daily lengthwise growth measurements of wool follicles were obtained using a microscopic micrometer. Cultured Hetian wool follicles were stained using the SACPIC method to reveal wool follicle structure, while sheep skin slices were used to observe cell proliferation by immunostaining and cell apoptosis using the TUNEL method. At the molecular biological level, keratin-associated protein (Kap) gene expression was studied using wool follicles cultured for various numbers of days in vitro. Effects of androgen concentrations on Hetian wool follicle growth and development were experimentally studied. EdU proliferation assays revealed that androgen promoted cell proliferation within wool follicle dermal papillae. TUNEL apoptosis detection demonstrated that androgen treatment could delay cell apoptosis. Quantitative reverse transcription polymerase chain reaction (qPCR) results demonstrated that gene expression level patterns of Hetian mountain sheep super-high sulfur protein. Kap1.1, KIF1.2, Kap2.12 and Kap4.2 gene expression level of the mountainous experimental group was significantly higher than plains Hetian sheep. An androgen concentration of 100 nM can promote the growth of Hetian wool follicle cells in vitro, resulting in overexpression of some genes of the Kap family.

Resumo Investigar a concentração ideal de andrógenos em cultura de folículos pilosos de carneiro Hetiano e detectar os efeitos da concentração de andrógenos na proliferação e apoptose de células foliculares, por meio de imunofluorescência e de determinação quantitativa, em tempo real, da fluorescência dos níveis de expressão gênica de proteína associada à queratina. Folículos pilosos foram isolados por microdissecção, e folículos de lã e pedaços de pele foram cultivados em várias concentrações de di-hidrotestosterona (DHT) em meio de cultura. Em seguida, medições diárias de crescimento longitudinal dos folículos capilares foram obtidas usando um micrômetro microscópico. Folículos de lã cultivados de Hetianos foram corados pelo método SACPIC para revelar a estrutura do folículo piloso, enquanto fatias de pele de carneiro foram usadas para observar a proliferação celular por imunocoloração e apoptose celular por meio do método TUNEL. Em âmbito da biologia molecular, a expressão gênica da proteína associada à queratina (Kap) foi estudada usando folículos capilares cultivados por vários dias, in vitro. Os efeitos das concentrações de andrógenos no crescimento e desenvolvimento dos folículos de lã de Hetianos foram estudados experimentalmente. Ensaios de proliferação de EdU revelaram que o andrógeno promoveu a proliferação celular dentro das papilas dérmicas do folículo piloso. A detecção de apoptose por TUNEL demonstrou que o tratamento com andrógeno poderia atrasar a apoptose celular. Os resultados da reação em cadeia da polimerase transcrição reversa quantitativa (qPCR) demonstraram que os padrões de expressão gênica da proteína de enxofre Kap1.1, KIF1.2, Kap2.12 e Kap4.2 foram significativamente maiores no grupo de ovinos Hetianos de montanha. Uma concentração de androgênio de 100 nM pode promover o crescimento de células foliculares de lã de Hetianos in vitro, resultando na superexpressão de alguns genes da família Kap.

Masculinization in common carp (Cyprinus carpio) by androgen immersion: The interaction effect of hormone concentration and immersion time / Masculinização na carpa comum (Cyprinus carpio) por imersão em androgênio: Efeito da interação da concentração hormonal e do tempo de imersão

Synthetic androgens (male hormones) administered to fish nursery are being used in aquaculture to avoid sexual differentiation and unwanted spawning at the eggs or the first feeding fry stage of fish. Present trial was conducted with the aim to produce male common carp (Cyprinus carpio) by egg immersion technique. Through this little insight, the effect of different hormone concentrations (17α-methyltestosterone @ HC:150, 300, 450 and 600 µgl-1) with immersion times (IT: 24, 48 and 72 hrs) and their interaction effect (HC x IT) on the hatching percentage of Cyprinus carpio eggs, percent survival and percent of male's production was evaluated specifically. Results showed that egg hatching percentage decreased with increased IT likewise, survival of treated fry was affected by increasing the IT (P<0.001). The main interaction effect of HC x IT showed that the highest percent of male individuals (95%) was obtained at 450-600 µgl-1 HC for 72 hrs IT, followed by 88-92.50% at 150-300 µgl-1 HC for 72-hrsof IT, 87.50% at 48-hrs of IT for rest of the hormone treatments, and lowest 47.50% was recorded in control (P<0.05). Increased percent male of Cyprinus carpio was obtained with increasing HC across all ITs. It was observed that the immersion treatment at 600µgl-1 for 72 hours was more effective to change the sex ratio of pre hatch Cyprinus carpio. A comparative outlook made from this experimental trial that sex induction of Cyprinus carpio by eggs immersion using synthetic male steroid hormone is an alternative safe technique of fish sex reversal in contrast to oral administration of hormone in fish feed.

Andrógenos sintéticos (hormônios masculinos) administrados ao viveiro de peixes estão sendo usados ​​na aquicultura para evitar a diferenciação sexual e a desova indesejada nos ovos ou no primeiro estágio de alimentação dos peixes. O presente estudo foi conduzido com o objetivo de produzir carpa comum masculina (Cyprinuscarpio) pela técnica de imersão em ovos. Com essa pequena percepção, o efeito de diferentes concentrações hormonais (17α-metiltestosterona @ HC: 150, 300, 450 e 600 µgl-1) com tempos de imersão (IT: 24, 48 e 72 horas) e seu efeito de interação (HC x IT) na porcentagem de eclosão dos ovos de Cyprinuscarpio, a porcentagem de sobrevivência e a porcentagem da produção masculina foram avaliadas especificamente. Os resultados mostraram que a porcentagem de incubação de ovos diminuiu com o aumento da TI da mesma forma, a sobrevivência dos alevinos tratados foi afetada pelo aumento da TI (P <0,001). O principal efeito de interação do HC x IT mostrou que o maior percentual de indivíduos do sexo masculino (95%) foi obtido com 450-600 µgl-1 HC por 72 horas de TI, seguido por 88-92,50% com 150-300 µgl-1 HC para 72 horas de TI, 87,50% às 48 horas de TI para o restante dos tratamentos hormonais, e 47,50% mais baixos foram registrados no controle (P <0,05). A porcentagem aumentada de macho de Cyprinuscarpio foi obtida com o aumento do HC em todas as TIs. Observou-se que o tratamento de imersão a 600µgl-1 por 72 horas foi mais efetivo na alteração da razão sexual do Cyprinuscarpio antes da eclosão. Uma perspectiva comparativa feita a partir deste ensaio experimental de que a indução sexual de Cyprinuscarpio por imersão de ovos usando hormônio esteróide masculino sintético é uma técnica alternativa segura de reversão do sexo em peixes, em contraste com a administração oral de hormônio na alimentação de peixes.

Behavioral cross-sensitization between testosterone and fenproporex in adolescent and adult rats

The abuse of psychoactive drugs is considered a global health problem. During the last years, a relevant number of studies have investigated the relationship between anabolic-androgenic steroids (AAS) and other psychoactive drugs. AAS, such as testosterone, can cause a dependence syndrome that shares many features with the classical dependence to psychoactive substances. Pre-clinical evidence shows that there are interactions between testosterone and psychoactive drugs, such as cocaine. However, few studies have been performed to investigate the effect of repeated testosterone treatment on behavioral effects of amphetamine derivatives, such as fenproporex. The purpose of the present study was to investigate the effects of repeated testosterone administration on fenproporex-induced locomotor activity in adolescent and adult rats. Adolescent male Wistar rats were injected with testosterone (10 mg/kg sc for 10 days). After 3 days, animals received an acute injection of fenproporex (3.0 mg/kg ip) and the locomotor activity was recorded during 40 min. Thirty days later, the same animals received the same treatment with testosterone followed by a fenproporex challenge injection as described above. Our results demonstrated that repeated testosterone induced behavioral sensitization to fenproporex in adolescent but not in adult rats. These findings suggest that repeated AAS treatment might increase the dependence vulnerability to amphetamine and its derivatives in adolescent rats.

Interaction of Anabolic Androgenic Steroids and Induced Tooth Movement in Rats

Abstract This study evaluated the interaction between tooth movement and two anabolic androgenic steroids (AAS), Deposteron® and Nebido®. One hundred Wistar rats were divided into 3 groups: control (C) n=30, Nebido experimental (N) n=35 and Deposteron experimental (D) n=35. The control group was subdivided into 6 subgroups: 1, 2, 3, 5, 7 and 14. The experimental groups were subdivided into 7 subgroups: 0, 1, 2, 3, 5, 7 and 14, which corresponded to the day of animal's euthanasia after applying orthodontic force. Orthodontic devices were used to induce tooth movement using 50 cN of reciprocal force between the maxillary right first molar and the maxillary incisors. After euthanasia, the tissues were processed and stained with hematoxylin and eosin (HE) and tartrate-resistant acid phosphatase (TRAP). Osteoclasts, Howship's lacunae and blood vessels were quantified. Groups N and D showed acceleration in the reorganization of the periodontal ligament compared to group C. The peak of the histological events occurred in group C on day 5 and in groups N and D on day 3 after installation of the orthodontic device. There was a statistically significant difference in the number of osteoclasts (p<0.05) between groups N3 and C3, and between groups N3 and D3. Supra-physiological doses of the AAS Nebido® and Deposteron® altered the number of osteoclasts, Howship's lacunae and blood vessels, accelerating the reorganization of the periodontal ligament, resulting in accelerated biological effects from the induced tooth movement in rats.

Resumo Este estudo avaliou a interação do movimento dentário entre dois esteróides anabólicos androgênicos (EAA), Deposteron® and Nebido®. Cem ratos Wistar foram divididos em 3 grupos: controle (C) n=30, Nebido experimental (N) n=35 e Deposteron experimental (D) n=35. O grupo controle foi subdivido em 6 subgrupos: 1, 2, 3, 5, 7 e 14. Os grupos experimentais foram subdivididos em 7 subgrupos: 0, 1, 2, 3, 5, 7 e 14, correspondendo ao dia da eutanásia do animal após aplicada a força ortodôntica. Um dispositivo ortodôntico foi utilizado para induzir a movimentação dentária com força recíproca de 50 cN entre o primeiro molar superior direito e os incisivos superiores. Após a eutanásia, o tecido foi processado e corado com hematoxilina e eosina (HE) e fosfatase ácida tartarato-resistente (TRAP). Osteoclastos, lacunas de Howship e vasos sanguíneos foram quantificados. Os grupos N e D demonstraram aceleração na reorganização do ligamento periodontal comparado ao grupo C. O pico dos eventos histológicos ocorreu no grupo C no dia 5 e nos grupos N e D no dia 3, após a instalação do dispositivo ortodôntico. Houve diferença estatisticamente significante no número de osteoclastos (p<0,05) entre os grupos N3 e C3 e entre os grupos N3 e D3. Doses supra-fisiológicas de EAA Nebido® and Deposteron® alteraram o número de osteoclastos, lacunas de Howship e vasos sanguíneos, acelerando a reorganização do ligamento periodontal, resultando na aceleração dos efeitos biológicos na movimentação dentária em ratos.

Testosterone and Voluntary Exercise, Alone or Together Increase Cardiac Activation of AKT and ERK1/2 in Diabetic Rats / Testosterona e Exercício Voluntário, Individualmente ou em Conjunto, Aumentam a Ativação Cardíaca de AKT e ERK1/2 em Ratos Diabéticos

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.

Family care of people with severe mental disorders: an integrative review / Cuidado familiar de pessoas com doenças mentais graves: uma revisão integrativa / Cuidado familiar de la persona con trastorno mental grave: una revisión integradora

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. .

Tratamento com andrógenos como possibilidade de melhoria do prognóstico reprodutivo em mulheres com envelhecimento ovariano / Treatment with androgens as a possibility to improve the reproductive outcome of women with ovarian aging

Justificativa: A resposta ao estímulo ovariano é uma peça-chave na reprodução assistida. Apesar dos recentes avanços das técnicas, pacientes com baixa reserva ovariana apresentam mau prognóstico e representam um desafio na medicina reprodutiva. Objetivo: Propor estratégia de melhoria do prognóstico reprodutivo em mulheres com idades superiores a 38 anos ou jovens com baixa contagem de folículos antrais, por meio do uso de testosterona previamente ao estímulo ovariano. Material e métodos: Levantamento de dados da literatura científica na área da medicina reprodutiva. Resultados e conclusões: O uso de androgênios em fases que antecedem a estimulação ovariana em ciclos de fertilização in vitro parece ser ótima ferramenta de melhoria da resposta à estimulação oocitária controlada em pacientes com mais de 38 anos ou com reserva ovariana diminuída. Melhora tanto a quantidade quanto a qualidade oocitária e aumenta as taxas de gestação e de nascido vivos.

Justification: The response to ovarian stimulation is a keyelement in assisted reproduction (AR). Despite recent advances in the techniques, patients with low ovarian reserve havepoor prognosis and represent a challenge in reproductive medicine.Objective: To propose a strategy to improve reproductive prognosis of women older than 38years or young women with low antral follicle count, through the use of testosterone prior to ovarian stimulus.Material and methods: Survey data from the scientific literature in the field of reproductive medicine. Results and conclusions: The use of androgens in stages preceding ovarian stimulation in IVF cycles seems to be great tool for improving oocyte response in oocyte controlled stimulation of patients older than 38 years or with diminished ovarian reserve, improving both quantityand quality of oocytes and increasing rates of pregnancy and live-born.

Effect of anabolic-androgenic steroids on semen parameters and serum hormonal levels in Iraqi male bodybuilders

This research aims at studying the influence of administration of anabolic androgenic steroids on the male reproductive health. Twenty four male bodybuilders were included in the study. The history of Anabolic Androgenic Steroids administration [AAS group] was recorded for 16 subjects [age =211.6 +/- years], while 8 subjects exercised only without AAS use [age =21.20.8 +/- years] and served as control group. All subjects of AAS group were asked to cease using AAS before being enrolled in the study. A sheet containing a detailed questionnaire was completed for each subject. Subjects of both groups were asked to visit the clinic [subsequent visits] for clinical evaluation of their health together with semen analysis. Blood was collected to determine serum hormonal changes. Semen analysis results indicated that, the use of AAS resulted in the impairment of spermatogenesis. Thus, sperm concentration and total sperm count increased significantly [P <0.05] within both AAS and control groups during the period of cessation, however, these parameters remained significantly low [P<0.05] in AAS group in comparison with the control group. Sperm agglutination increased significantly within AAS group [P<0.05]. Both sperm agglutination and round cells increased significantly [P<0.05] in AAS group as compared with the control group. Likewise gonadotropins: Follicle-Stimulating Hormone [FSH] and Luteinizing Hormone [LH] increased significantly [P<0.05] in AAS group, 12 weeks after the cessation of AAS as compared to baseline. Although prolactin level was within the normal range in AAS group, it was significantly low [P<0.05] in AAS group as compared to the control. These findings collectively indicated that, the use of AAS drugs have an ill effect on the general health of the users in addition to a profound effect on the reproductive functions. This study has also opened the road for further studies in Iraq concerned with the abuse of anabolic steroids which may constitute on the long run a major source of health and social problems

Corticosteroid physiology and principles of therapy.

The adrenal cortex secretes glucocorticoids (GC), mineralocorticoids (MC) and androgens. GC maintain homeostasis, MC regulate fluid and electrolyte balance and adrenal androgens contribute to development of secondary sexual characteristics. Pharmacologic GC therapy is frequently indicated in the pediatric age group. Besides having many important side effects, prolonged high dose systemic GC therapy has a suppressive effect on endogenous steroid production. Therefore, GC therapy should be withdrawn gradually and stopped based on assessment of hypothalamo-pituitary-adrenal (HPA) axis recovery. Patients with HPA axis suppression require physiological replacement of GC along with enhancement of doses during periods of stress. Due to its immunosuppressive effects, issues about safety and efficacy of live virus vaccines in patients receiving systemic high dose GC therapy must be borne in mind.

p53 overexpression represses androgen-mediated induction of NKX3.1 in a prostate cancer cell line

Prostate cancer is a disease involving complicated multiple-gene alterations. Both NKX3.1 and p53 are related to prostate cancer and play crucial roles in prostate cancer progression. However, little is known about the relationships and interactions between p53 and NKX3.1 in prostate cancer. We found that NKX3.1 expression is down-regulated by over-expression of wild type (wt) p53 in prostate cancer LNCaP cells. NKX3.1 is down-regulated at both the mRNA and protein levels by p53 over- expression due to either transient transfection of exogenous p53 or induction of endogenous p53. p53 over-expression represses androgen-induced transactivation of NKX3.1 by inhibiting the promoter of the androgen acceptor (AR) gene and by blocking AR-DNA binding activity. In addition, transfection with the p21 expression vector (pPSA-p21) showed that p21 does not reduce NKX3.1 expression, indicating that NKX3.1 expression is not the result of nonspecific effects of cell growth arrest. Our results provide biochemical and cellular biologic evidence that NKX3.1 is down-regulated by p53 over-expression in prostate cancer cells.

Morphological changes induced by testosterone in the mammary glands of female Wistar rats

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.

Direct and Indirect Effects of Androgens on Survival of Hematopoietic Progenitor Cells In Vitro

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.

Risks and benefits of hormone replacement therapy in older men

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.

Testosterone Causes Simultaneous Decrease of Ca2+i and Tension in Rabbit Coronary Arteries: by Opening Voltage Dependent Potassium Channels

The relationship between the level of testosterone and the incidence of coronary heart disease is still controversial in the view of the results of clinical and epidemiologic studies. This uncertainty might be partly due to relatively small number of experimental studies undertaken to investigate the cellular mechanism underlying the vascular responses to testosterone. To further investigate the cellular mechanisms of testosterone with respect to vascular response, we investigated the effect of testosterone on contractility and intracellular Ca2+ regulation in a rabbit coronary artery and evaluated the underlying mechanism of testosterone-induced changes of coronary vascular tone by using various pharmacological blockers. Testosterone was found to relax rabbit coronary arteries in a dose-dependent manner, and no significant difference was found in the relaxation response to testosterone with or without endothelium. Similar results were obtained in male and non-pregnant female rabbit coronary arteries. The relaxation response of rabbit coronary arteries to testosterone was greater for PGF2alpha-contracted rings than for KCl contracted rings, which suggest the involvement of K+ channels. Furthermore, the relaxation response to testosterone was significantly reduced by 4-aminopyridine, a sensitive blocker of voltage dependent K+ channels, but not by low doses of tetraethylammonium or iberiotoxin, a Ca2+ activated K+ channel blocker. Testosterone simultaneously reduced the intracellular Ca2+ concentration ([Ca2+]i) and tension, and 4-AP effectively antagonized the testosterone-induced change of [Ca2+]i and tension. Therefore, it may be concluded that the stimulation of voltage dependent K channels is responsible, at least in part, for the testosterone-induced relaxation of rabbit coronary arteries.

Urinary proteins and pheromonal communication in mammals.

Urinary proteins play a significant role as pheromones and pheromone-binders in mammalian reproduction and social behaviour. The present study was carried out to quantify the urinary proteins in five different mammalian species viz mouse, rat, rabbit, bovine and human. The results revealed that the male rodents excrete large amounts of urinary protein as compared to that of other mammals. In addition, the male mammals excrete a higher quantity of protein than do the females., suggesting the role of androgens in excretion of protein. The presence of higher concentration of urinary proteins in rodents suggests that the rodents depend more on urinary proteins for olfactory/social communication.

Immunochemical characterization and antifertility effect of an androgen independent antigen of spermatozoa identified by a monoclonal antibody (D7G3).

Monoclonal antibody, (mAb) D7G3, directed to human spermatozoa and cross-reactive with mouse and rat spermatozoa was found to be a sperm agglutinating antibody. It reacted with antigen present on the post acrosomal region of human spermatozoa and acrosomal region of mouse spermatozoa. The antigen reacting with mAb D7G3 was localized in mouse testicular germ cells and Sertoli cells. It was also localized in the epithelium and spermatozoa of the caput, corpus and cauda epididymides. In addition, the antigen was detected in the epithelial cells and secretions of the prostate and seminal vesicle. The mAb D7G3 reacted with a band of molecular mass 16 kDa in testicular and epididymal sperm and protein preparations of ventral prostate. In the seminal vesicle, an additional band of molecular mass 36 kDa was also identified. The effect of castration on the expression of proteins was studied in the rat. Immunohistochemical localization and Western blotting experiments showed that the antigens identified by the mAb D7G3 was detectable in the epididymis, ventral prostate and seminal vesicle after two weeks of castration. In the seminal vesicle, three additional bands were identified by mAb D7G3 following castration. The expression of this antigen throughout spermatogenesis and sperm maturation indicated that it may have an important biological function. A polyclonal antiserum directed to the 16 kDa mouse epididymal sperm protein was raised in rabbits. Passive immunization of female mice with this antibody caused a significant reduction in fertility only if administered 24 hours prior to mating, indicating that the antibody inhibited a pre-fertilization event by inhibiting sperm function.

Androgenos em ginecologia / Androgens in gynecology

O emprego dos androgenos em ginecologia constitui o motivo deste estudo onde säo abordadas as açöes biológicas destes hormonios, as principais indicaçöes terapeuticas (estados intersexuais, liquem escleroso, síndrome de deficiência androgenica na mulher, alteraçöes emocionais e da libido, endometriose, osteoporose, climatério e câncer da mama) e os efeitos colaterais

Effects of prolactin and androgens on enzymes of carbohydrate metabolism in prostate of castrated bonnet monkeys Macaca radiata (Geoffroy).

Effects of prolactin (PRL), bromocriptine (Br), testosterone propionate (TP), dihydrotestosterone (DHT) and the combinations of these androgens with PRL/Br on the specific activities of caudal and cranial prostatic cellular enzymes involved in carbohydrate metabolism in castrated mature bonnet monkeys have been studied. Castration decreased all the enzymes studied such as hexokinase (HK), 6-phosphofructokinase (6-PFK), glyceraldehyde-3-phosphate dehydrogenase (G-3-PD), pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G-6-PD) and 6-phosphogluconate dehydrogenase (6-PGD) in the cranial and caudal prostates. PRL elevated the activities of all the enzymes above normal except G-3-PD of cranial lobe. In the caudal lobe, PRL brought back the activities of HK, PFK, PK, G-6-PD to normal and 6-PGD above normal except G-3-PD. TP/DHT treatment increased all the enzymes in both the lobes. PRL given along with TP/DHT further enhanced the androgen action with regard to HK, PK, G-6-PD and 6-PGD of cranial and PFK, G-3-PD, PK, G-6-PD and 6-PGD of caudal lobe. Br treatment did not produce any alteration of these enzymes in both the lobes. In the cranial lobe, during Br+TP/DHT treatment, the stimulating effects of androgen were unaffected on all the enzymes except PK. On the other hand in the caudal, the stimulatory effects of androgens were affected and the activities of HK, PFK, PK and 6-PGD were significantly decreased. The present results suggest that PRL has a direct as well as a synergistic action with androgens on enzymes of EMP and HMP shunt in the prostates of monkeys.