Extra nuclear localization of steroid receptors and non genomic activation mechanisms

Los receptores de hormonas esteroides han sido considerados históricamente como factores de transcripción nucleares. Sin embargo, en los últimos años surgieron evidencias que indican que su activación desencadena eventos rápidos, independientes de la transcripción y que involucran a diferentes segundos mensajeros; muchos de estos receptores han sido localizados en la membrana celular. Por otra parte, se han caracterizado varios receptores de hormonas esteroides noveles, de estructura molecular diferente al receptor clásico, localizados principalmente en la membrana celular. Esta revisión enfoca los diferentes efectos iniciados por los glucocorticoides, mineralocorticoides, andrógenos, estrógenos y progesterona, y los posibles receptores involucrados en los mismos.Steroid hormone receptors have been historically considered as nuclear transcription factors. Nevertheless, in the last years, many of them have been detected in the cellular membrane. It has been postulated that their activation can induce transcription independent rapid events involving different second messengers. In addition, several novel steroid hormone receptors, showing a different molecular structure than the classical ones, have also been characterized and most of them are also located in the plasmatic membrane. This review focuses on the variety of effects initiated by glucocorticoids, mineralocorticoids, androgens, estrogens and progesterone, and the possible receptors involved mediating these effects.Fil: Bottino, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentin

The MPA mouse breast cancer model: evidence for a role of progesterone receptors in breast cancer

More than 60% of all breast neoplasias are ductal carcinomas expressing estrogen (ER) and progesterone receptors (PR). In contrast, most of the spontaneous, chemically or MMTV induced tumors, as well as tumors arising in genetically modified mice do not express hormone receptors. We developed a model of breast cancer in which the administration of medroxyprogesterone acetate (MPA) to BALB/c female mice induces mammary ductal carcinomas with a mean latency of 52 weeks and an incidence of about 80%. These tumors are hormone-dependent, metastatic, express both ER and PR, and are maintained by syngeneic transplants. The model has been further refined to include mammary carcinomas that evolve through different stages of hormone dependency, as well as several hormone-responsive cell lines. In this review, we describe the main features of this tumor model, highlighting the role of PR as a trigger of key signaling pathways mediating tumor growth. In addition, we discussthe relevance of this model in comparison with other currently used breast cancer models pointing out its advantages and limitations and how, this model may be suitable to unravel key questions in breast cancer.Fil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Lamb, Caroline Ana. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Fabris, Victoria Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Helguero, Luisa A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Soldati, Rocío. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Bottino, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Giulianelli, Sebastian Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Wargon, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; ArgentinaFil: Molinolo, Alfredo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Public Health Service. National Institute Of Health; Estados Unido

The effect of D-aspartate on luteinizing hormone-releasing hormone, α-melanocyte-stimulating hormone, GABA and dopamine release

Since D-aspartate stimulates prolactin and LH release, our objective was to determine whether D-aspartate modifies the release of hypothalamic and posterior pituitary factors involved in the control of their secretion and whether its effects on these tissues are exerted through NMDA receptors and mediated by nitric oxide. In the hypothalamus, D-aspartate stimulated luteinizing hormone-releasing hormone (LHRH), alpha-melanocyte-stimulating hormone (alpha-MSH) and GABA release and inhibited dopamine release through interaction with NMDA receptors. It increased nitric oxide synthase (NOS) activity, and its effects on LHRH and hypothalamic GABA release were blunted when NOS was inhibited. In the posterior pituitary gland, D-aspartate inhibited GABA release but had no effect on dopamine or alpha-MSH release. We report that D-aspartate differentially affects the release of hypothalamic and posterior pituitary factors involved in the regulation of pituitary hormone secretion.Fil: Pampillo, Macarena. No especifíca;Fil: Scimonelli, Teresa. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Farmacología; ArgentinaFil: Bottino, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Duvilanski, Beatriz Haydee. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Rettori, Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Seilicovich, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; ArgentinaFil: Lasaga, Mercedes Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Biomédicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Biomédicas; Argentin

Efeito da concentração de bactérias probióticas como imunomodulador da produção de anticorpos antirrábicos em bovinos vacinados

This study evaluated the effects of supplementation with a combination of probiotic microorganisms, added at different concentrations to the mineral mixture, on the production of serum antibodies against rabies virus in cattle vaccinated with a single dose of rabies vaccine. Forty-two male Nellore cattle, aged 12 months, were randomly divided into three groups (n = 14): the control group (CG) received 70 grams of mineral mixture/animal/day; and the 2 gram probiotic group (G2P) and 8 gram probiotic group (G8P) received 70 grams of mineral mix/animal/day with 2 and 8 grams added, respectively, of a combination of probiotic microorganisms (Lactobacillus acidophilus, Streptococcus faecium, Bifidobacterium thermophilum and Bifidobacterium longum). Individual antibody titers were determined using a neutralization in cell-based rapid fluorescent focus inhibition test (RFFIT) technique. One-way analysis of variance (one-way ANOVA) was used with contrasts using the Tukey method to determine whether the experimental groups differed within each time point, and the paired t-test was used to determine whether differences occurred between time points within each group. The level of significance was set at 5%. There were statistically significant differences between the mean serum concentrations of the CG and G8P groups at 30 and 60 days after the first vaccination, and at 60 days, 100% of the animals maintained minimum titers of protective antibodies only in the G8P group. There was also improvement in the production of antibodies in the G2P group compared with the CG after 30 and 60 days, but this difference was not statistically significant. In conclusion, increasing doses of probiotic added to the mineral mix beneficially affected the rabies humoral immune response, as determined by serum antibodies, and enabled the maintenance of minimum protective titers for a longer period in previously vaccinated cattle.Esse estudo avaliou o efeito da suplementação de uma associação de microrganismos probióticos, adicionados à mistura mineral em diferentes doses, na produção de anticorpos séricos antirrábicos em bovinos primovacinados. Os Quarenta e dois bovinos Nelore machos, com idade de 12 meses, foram divididos em três grupos (n=14): grupo controle (GC) recebeu 70 gramas de mistura mineral/animal/dia; grupos probiótico 2 gramas (G2P) e 8 gramas (G8P) receberam 70 gramas de mistura mineral/animal/dia adicionados respectivamente de 2 e 8 gramas de probióticos (Lactobacillus acidophilus, Streptococcus faecium, Bifidobacterium thermophilum e Bifidobacterium longum). títulos individuais de anticorpos antirrábicos foram determinados por meio da técnica de soroneutralização em células baseado no rapid fluorescent focus inhibition test (RFFIT). Os resultados obtidos foram comparados pelo teste t não pareado, com 5% de nível de significância. Houve diferenças estatísticas significativas entre as médias de concentrações séricas entre os grupos GC e G8P, após 30 e 60 dias da primovacinação e após 60 dias, somente o G8P manteve 100% com títulos de anticorpos protetores mínimos. Houve também melhora na produção de anticorpos no grupo G2P em relação ao GC, após 30 e 60 dias, porém não significativa. Conclui-se que as doses crescentes de probiótico adicionadas na mineral interferiram beneficamente na resposta imune humoral antirrábica, determinada pela concentração sérica de anticorpos, assim como permitiu a manutenção por um período maior os títulos protetores mínimos nos bovinos primovacinados

Glutamate Induces Apoptosis in Anterior Pituitary Cells through Group II Metabotropic Glutamate Receptor Activation

Glutamate can induce neuronal cell death by activating ionotropic glutamate receptors (iGluRs) as well as metabotropic glutamate receptors (mGluRs). In the present study, we investigated whether glutamate induces apoptosis of cultured anterior pituitary cells from female rats. Glutamate (1 mM) significantly reduced the metabolic activity of viable cells and increased the percentage of terminal deoxynucleotidyl transferasemediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive cells and caspase-3 activity in anterior pituitary cells. The inhibitory effect of glutamate on the viability of anterior pituitary cells was not observed in the presence of [2S]-α-ethylglutamic acid (0.75 mM), a specific group II mGluR antagonist. Also, (2S,1′S,2′S)-2-(carboxycyclopropyl) glycine (LCCG-I; 0.75 mM), a specific group II mGluR agonist, reduced viability and increased the percentage of TUNEL-positive anterior pituitary cells. Group I and III mGluRs and iGluRs agonists failed to modify the metabolic activity of anterior pituitary cells. Glutamate and LCCG-I increased the percentage of TUNEL-positive lactotropes and somatotropes. The subunit mGluR2/3, belonging to group II mGluR, was localized in these cell types. Glutamate increased nitric oxide (NO) synthase (NOS) activity and inducible NOS expression in anterior pituitary cells. N-methyl-L-arginine (NMMA, 0.5 mM), a NOS inhibitor, potentiated the apoptotic effect of glutamate in anterior pituitary cells, indicating that NO may restrain glutamate-induced apoptosis. Incubation of anterior pituitary cells with a cAMP analog (N6, 2′-o-dibutyryladenosine 3′, 5′-cyclic monophosphate; 1 mM) attenuated the apoptosis induced by glutamate. Glutamate and LCCG-I decreased prolactin release from anterior pituitary cells. N6, 2′-o-dibutyryladenosine 3′, 5′-cyclic monophosphate reversed the inhibitory effect of glutamate on prolactin release, but NMMA failed to modify it. Our data show that glutamate induces apoptosis of lactotropes and somatotropes through group II mGluR activation, probably by decreasing cAMP synthesis.Fil: Bottino, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Pampillón González, María Cristina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Pisera, Daniel Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Jaita, Gabriela Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Duvilanski, Beatriz Haydee. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Seilicovich, Adriana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Lasaga, Mercedes Isabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; ArgentinaFil: Caruso, Carla Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Investigaciones Médicas. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Investigaciones Médicas; Argentin

Classical membrane progesterone receptors in murine mammary carcinomas: agonistic effects of progestins and RU-486 mediating rapid non-genomic effects.

In this article, we demonstrate the expression of functional progesterone binding sites at the cell membrane in murine mammary carcinomas that are stimulated by progestins and inhibited by antiprogestins. Using confocal immunofluorescence, ligand binding and cell compartment-specific western blots, we were able to identify the presence of the classical progesterone receptors. Medroxyprogesterone acetate (MPA) and RU-486 (1 × 10(-11) and 1 × 10(-8) M) behaved as agonists activating extracellular signal-regulated kinases (ERKs) and progestin-regulated proteins, except for Cyclin D1 and Tissue factor which failed to increase with 1 × 10(-8) M RU-486, an experimental condition that allows PR to bind DNA. These results predicted a full agonist effect at low concentrations of RU-486. Accordingly, at concentrations lower than 1 × 10(-11) M, RU-486 increased cell proliferation in vitro. This effect was abolished by incubation with the ERK kinase inhibitor PD 98059 or by OH-tamoxifen. In vivo, at a daily dose of 1.2 μg/kg body weight RU-486 increased tumor growth, whereas at 12 mg/kg induces tumor regression. Our results indicate that low concentrations of MPA and RU-486 induce similar agonistic non-genomic effects, whereas RU-486 at higher concentrations may inhibit cell proliferation by genomic-induced effects. This suggests that RU-486 should be therapeutically administered at doses high enough to guarantee its genomic inhibitory effect.Fil: Bottino, Maria Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Cerliani, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Rojas, Paola Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Giulianelli, Sebastian Jesus. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Soldati, Rocío. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Mondillo, Carolina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Gorostiaga, Maria Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Pignataro, Omar Pedro. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Calvo, Juan Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Gutkind, Silvio J.. National Institutes of Health. National Institute of Dental and Craniofacial Reasearch; Estados UnidosFil: Amornphimoltham, Panomwat. National Institutes of Health. National Institute of Dental and Craniofacial Reasearch; Estados UnidosFil: Molinolo, Alfredo A.. National Institutes of Health. National Institute of Dental and Craniofacial Reasearch; Estados UnidosFil: Luthy, Isabel Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; ArgentinaFil: Lanari, Claudia Lee Malvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina; Argentin

Clinical nutrition in surgical oncology: Young AIOM-AIRO-SICO multidisciplinary national survey on behalf of NutriOnc research group

Malnutrition is a common condition in cancer patients which is usually associated with functional limitations, as well as increased morbidity and mortality. Based on the support of the young sections of Italian Association of Medical Oncology (AIOM), Italian Association of Radiotherapy and Clinical Oncology (AIRO) and Italian Society of Surgical Oncology (SICO) merged into the NutriOnc Research Group, we performed a multidisciplinary national survey with the aim to define the awareness of nutritional issues among healthcare professionals delivering anticancer care. The questionnaire was organized in four sections, as follows: Knowledge and practices regarding Nutritional Management of cancer patients; Timing of screening and assessment of Nutritional Status; Nutritional Treatment and prescription criteria; Immunonutrition and educational topics. The modules focused on esophagogastric, hepato-bilio-pancreatic and colorectal malignancies. Overall, 215 physicians completed the survey. As regards the management of Nutritional Status of cancer patients, many responders adopted the ERAS program (49.3%), while a consistent number of professionals did not follow a specific validated nutritional care protocol (41.8%), mainly due to lack of educational courses (14.5%) and financial support (15.3%). Nearly all the included institutions had a multidisciplinary team (92%) to finalize the treatment decision-making. Cancer patients routinely underwent nutritional screening according to 57.2% of interviewed physicians. The timing of nutritional assessment was at diagnosis (37.8%), before surgery (25.9%), after surgery (16.7%), before radiochemotherapy (13.5%) and after radiochemotherapy (7%). Most of the responders reported that nutritional status was assessed throughout the duration of cancer treatments (55.6%). An important gap between current delivery and need of nutritional assessment persists. The development of specific and defined care protocols and the adherence to these tools may be the key to improving nutritional support management in clinical practice