Effect of hyperthyroidism on circulating prolactin and hypothalamic expression of tyrosine hydroxylase, prolactin signaling cascade members and estrogen and progesterone receptors during late pregnancy and lactation in the rat

Hyperthyroidism (HyperT) compromises pregnancy and lactation, hindering suckling-induced PRL release. We studied the effect of HyperT on hypothalamic mRNA (RT-qPCR) and protein (Western blot) expression of tyrosine hydroxylase (TH), PRL receptor (PRLR) and signaling pathway members, estrogen-α (ERα) and progesterone (PR) receptors on late pregnancy (days G19, 20 and 21) and early lactation (L2) in rats. HyperT advanced pre-partum PRL release, reduced circulating PRL on L2 and increased TH mRNA (G21 and L2), p-TH, PRLR mRNA, STAT5 protein (G19 and L2), PRLR protein (G21) and CIS protein (G19). PRs mRNAs and protein decreased on G19 but afterwards PRA mRNA (G20), PRB mRNA (G21) and PRA mRNA and protein (L2) increased. ERα protein increased on G19 and decreased on G20. Thus, the altered hypothalamic PRLR, STAT5, PR and ERα expression in hyperthyroid rats may induce elevated TH expression and activation, that consequently, elevate dopaminergic tone during lactation, blunting suckling-induced PRL release and litter growth.Fil: Pennacchio, Gisela Erika. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Neira, Flavia Judith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Soaje, Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Jahn, Graciela Alma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Valdez, Susana Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; Argentin

Long-term effects od neonatal hypoxia on anxiety-related behaviors and hormonal response to acute stress

Neonatal lesions in the brain have less severe effects than in adults due to the neuronal plasticity of the developing nervous system, although they can cause cognitive and behavioral sequelae. Previously, we found that neonatal hypoxia (NH) transiently affected the expression of proteins associated with synaptogenesis in certain brain areas. The intermingled neural circuits controlling both stress and anxiety suggest a strong relationship between stress experiences and anxiety in both healthy and pathological conditions. We evaluated the long-term effects of NH on anxiety parameters and in stress-induced hormone release in adult female (estrous day of rat cycle) and male rats. Sprague Dawley rats at 4 Post-Natal Day (PND) were exposed to an atmosphere of low oxygen level (6.5% O2 and 93.5% N2) for 70 min. 4PND control pups were exposed to normal oxygen levels (Co) for 70 min. The humidity and temperature conditions were controlled. Pups were then returned with their mother until weaned, and then they were allowed to grow. At 3 months of age, both groups of rats were subjected to two tests, Elevated Plus Maze (EPM) to measure anxiety parameters and a stressful challenge to determine hormone response to acute stress (exposure to ether vapors for 2 min). EPM reflected an unconditional aversion to heights and open spaces, an anxiogenic behavior. The hormonal response to stress included the release of pituitary prolactin (PRL), adrenal progesterone (P4), and adrenal corticosterone (CORT). Blood samples were collected before and after 5 min of stress exposure for serum hormone determinations by RIA. In the EPM test, both female and male hypoxic rats increased the number of entries to the open arms (OA) and the time spent in the OA compared to Co (P<0.05). The results obtained indicated an anxiolytic-related behavior induced by NH, that was higher in female than in male hypoxic rats. Basal levels (unstressed) of PRL and P4 in NH rats remained similar to Co ones in both sexes. Only in female rats, NH increased the basal levels of CORT compared Co rats (P<0.05). In female and male rats, the hormonal release of PRL, P4, and CORT induced by stress, were differentially affected by NH. Hypoxia attenuated the stress-induced PRL secretion in female rats (P<0.05) while this response was blocked in males. The release of CORT by stress was blunted in both sexes by NH. The release of P4 by stress was inhibited in NH female but it was preserved in male rats. In conclusion, the long-term effects of NH were influenced by sex. NH altered the anxiety levels and the hormonal response to stress in adulthood. The alterations caused by NH at the brain level could be influencing the appropriate response to situations of stress and anxiety in adulthood.Fil: Neira, Flavia Judith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Torrecilla, Norma Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Pennacchio, Gisela Erika. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Soaje, Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Jahn, Graciela Alma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Seltzer, Alicia Mabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentina. Universidad Nacional de Villa Mercedes. Escuela de Cs. de la Salud; ArgentinaFil: Valdez, Susana Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaXXXVII Reunión Científica Anual de la Sociedad de Biología de CuyoSan LuisArgentinaSociedad de Biología de Cuy

Hipertiroidismo incrementa el crecimiento fetal, el infiltrado leucocitario placentario y los niveles de corticosterona y prolactina en gestación tardía

Las disfunciones tiroideas pueden generar profundas alteraciones endócrinas y trastornos reproductivos durante la etapa gestacional. Sin embargo, se desconoce si el hipertiroidismo (H) puede modular la expresión de citoquinas e infiltrado celular leucocitario en placenta. Por lo antes mencionado, el objetivo del presente trabajo fue determinar la influencia del H en: i) los niveles séricos de hormonas inmunomoduladoras como prolactina y corticosterona, ii) infiltrado leucocitario, iii) la expresión de receptores hormonales iv) y citoquinas (IL-17, IL-8, VEGF, IL-1 β y TGF β). Para esto, fueron empleadas ratas Wistar hembras de 10-12 semanas de edad; las cuales fueron inyectadas diariamente con T4 (0.1 o 0.25 mg/kg s.c) con el objetivo de inducir H o con vehículo (grupo control)

Desmoglein-4 deficiency exacerbates psoriasiform dermatitis in rats while psoriasis patients displayed a decreased gene expression of DSG4

Desmogleins are involved in cell adhesion conferring structural skin integrity. However, their role in inflammation has been barely studied, and whether desmoglein-4 modulates psoriasis lesions is completely unknown. In this study, we assessed the impact of desmoglein-4 deficiency on the severity of imiquimod (IMQ)-induced skin inflammation and psoriasiform lesions. To this end, desmoglein-4−/− Oncins France Colony A (OFA) with Sprague–Dawley (SD) genetic background were used. Additionally, human RNA-Seq datasets from psoriasis (PSO), atopic dermatitis (AD), and a healthy cohort were analyzed to obtain a desmosome gene expression overview. OFA rats displayed an intense skin inflammation while SD showed only mild inflammatory changes after IMQ treatment. We found that IMQ treatment increased CD3+ T cells in skin from both OFA and SD, being higher in desmoglein-4-deficient rats. In-depth transcriptomic analysis determined that PSO displayed twofold less DSG4 expression than healthy samples while both, PSO and AD showed more than three-fold change expression of DSG3 and DSC2 genes. Although underlying mechanisms are still unknown, these results suggest that the lack of desmoglein-4 may contribute to immune-mediated skin disease progression, promoting leukocyte recruitment to skin. Although further research is needed, targeting desmoglein-4 could have a potential impact on designing new biomarkers for skin diseases.Fil: Moreno Sosa, María Tamara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Sánchez, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Pietrobon, Elisa Olivia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Fernandez Muñoz, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Zoppino, Felipe Carlos Martin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Neira, Flavia Judith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Germano, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Cargnelutti, Diego Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Innocenti Badano, Alicia Carolina. Gobierno de la Provincia de Mendoza. Hospital Luis Lagomaggiore.; ArgentinaFil: Jahn, Graciela Alma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Valdez, Susana Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Mackern Oberti, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentin

Control de lh sobre la migración e invasión de células de cáncer de mama vía src/fak/paxillin y cortactin/cdc-42/n-wasp

El cáncer de mama es una problemática a nivel mundial. La elevada tasa de mortalidad por este tipo de cáncer se debe a su proceso de metástasis, ya que este evento es difícil de tratar y controlar. Por este motivo, la búsqueda de nuevas terapias tiene como objetivo, evitar el proceso de metástasis celular. La hormona luteinizante (LH) es sintetizada y secretada por la glándula pituitaria y sus efectos sobre el cáncer de mama son poco conocidos. La movilidad celular es un evento fundamental en la migración e invasión celular. Un elevado número de proteínas reguladoras son reclutadas para dirigir la dinámica funcional de estos procesos. Nuestros resultados previos han demostrado como LH regula la movilidad de células tumorales de mama, a través del remodelamiento rápido del citoesqueleto actínico mediante las proteínas ROCK-2 y moesin. Por ello, en este trabajo, se propuso continuar profundizando las bases moleculares de estos procesos. Los resultados indican que LH provoca un rápido remodelamiento actínico, a través de su receptor (LHR), que conduce hacia la activación de N-WASP, mediante una vía de señalización mediada por proteína G/Src/FAK/Paxillin/Cdc42/N-WASP/Arp2-3. Además, se pudo determinar una regulación adicional entre las proteínas Src/FAK/Cortactin hacia N-WASP/complejo Arp2/3, promoviendo la migración e invasión celular.Breast cancer is a worldwide problem. The high mortality rate by this type of cancer is due to the process of metastasis. Since this event is difficult to treat and to control, the search for new therapies aims to prevent cell metastasis. Luteinizing hormone (LH) is synthesized and secreted by the pituitary gland and its effects on breast cancer are poorly understood. Cell mobility is a key event in cell migration and invasion. A large number of regulatory proteins are recruited to direct the functional dynamics of these processes. Our previous results have shown that LH regulates breast cancer cell motility, through the rapid remodeling of the actin cytoskeleton through ROCK-2 and moesin proteins. Therefore, in this work it was decided to further deepen the molecular basis of these process. The results indicate that LH causes a rapid actinic remodeling, via LHR receptor. This leads to the activation of N-WASP, through a signaling pathway mediated by protein G/Src/FAK/Paxillin/Cdc42/N- WASP/Arp2-3. In addition, it was observed an additional regulation via Arp2/3 complex and Src/FAK/Cortactin proteins towards N-WASP promoting migration and cell invasion.Fil: Neira, Flavia Judith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

Prenatal Amphetamine-Induced Dopaminergic Alteration in a Gender- and Estrogen-Dependent Manner

Prenatal exposure to amphetamine induces changes in dopamine receptors in mesolimbic areas and alters locomotor response to amphetamine during adulthood. Sex differences have been reported in amphetamine-induced brain activity and stress sensitivity. We evaluated the effects of prenatal amphetamine exposure on locomotor activity, dopamine receptors and tyrosine hydroxylase mRNA expression in nucleus accumbens and caudate-putamen in response to amphetamine challenge in adult female and male rats. The role of estrogen in the response to restraint stress was analyzed in ovariectomized, prenatally amphetamine-exposed rats. Pregnant rats were treated with d-amphetamine during days 15–21 of gestation. Nucleus accumbens and caudate-putamen were processed for mRNA determination by real-time PCR. In nucleus accumbens, higher mRNA dopamine (D3) receptor expression was found in basal and d-amphetamine-challenge conditions in female than male, and prenatal amphetamine increased the difference. No sex differences were observed in caudate-putamen. Basal saline-treated females showed higher locomotor activity than males. Amphetamine challenge in prenatally amphetamine-exposed rats increased locomotor activity in males and reduced it in females. In nucleus accumbens, estrogen diminished mRNA D1, D2 and D3 receptor expression in basal, and D1 and D3 in ovariectomized stressed rats. Estrogen prevented the increase in tyrosine hydroxylase expression induced by stress in ovariectomized prenatally exposed rats. In conclusion, estrogen modulates mRNA levels of D1, D2 and D3 receptors and tyrosine hydroxylase expression in nucleus accumbens; prenatal amphetamine-exposure effects on D3 receptors and behavioral responses were gender dependent.Fil: Pennacchio, Gisela Erika. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Santonja, Florencia Eleonora. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Neira, Flavia Judith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Bregonzio Diaz, Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Farmacología Experimental de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Farmacología Experimental de Córdoba; ArgentinaFil: Soaje, Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Medicas. Instituto de Fisiologia; Argentin

Paxillin, a novel controller in the signaling of estrogen to FAK/N-WASP/Arp2/3 complex in breast cancer cells

Breast cancer is the major cause of cancer-related death in women. Its treatment is particularly difficult when metastasis occurs. The ability of cancer cells to move and invade the surrounding environment is the basis of local and distant metastasis. Cancer cells are able to remodel the actin cytoskeleton, which requires the recruitment of numerous structural and regulatory proteins that modulate actin filaments dynamics, including Paxillin or the Neural Wiskott-Aldrich Syndrome Protein (N-WASP). We show that 17-β estradiol (E2) induces phosphorylation of Paxillin and its translocation toward membrane sites where focal adhesion complexes are assembled. This cascade is triggered by a Gαi1/Gβ protein-dependent signaling of estrogen receptor α (ERα) to c-Src, focal adhesion kinase (FAK) and Paxillin. Within this complex, activated Paxillin recruits the small GTPase Cdc42, which triggers N-WASP phosphorylation. This results in the redistribution of Arp2/3 complexes at sites where membrane structures related to cell movement are formed. Recruitment of Paxillin, Cdc42 and N-WASP is necessary for cell adhesion, migration and invasion induced by E2 in breast cancer cells. In parallel, we investigated whether Raloxifene (RAL), a selective estrogen receptor modulator (SERMs), could inhibit or revert the effects of E2 in breast cancer cell movement. We found that, in the presence of E2, RAL acts as an ER antagonist and displays an inhibitory effect on estrogen-promoted cell adhesion and migration via FAK/Paxillin/N-WASP. Our findings identify an original mechanism through which estrogen regulates breast cancer cell motility and invasion via Paxillin. These results may have clinical relevance for the development of new therapeutic strategies for cancer treatment.Fil: Shortrede, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Uzair, Ivonne Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Neira, Flavia Judith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Flamini, Marina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Sanchez, Angel Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

Hipocampal hormone receptors expression in late pregnant and lactating rats: effect of mild hyperthyroidism

Thyroid disorders are associated with anxiety, depression and disturb responses to stress. The effect of stress is associated with functional changes in hippocampus (HpC) and hypothalamus by activating the hypothalamichypophysis-adrenal axis (HHA) and glucocorticoid release induced to stress. This response is physiologically attenuated during lactation. We found that mild hyperthyroidism (HyperT) increases stress-induced serum prolactin (PRL) and corticosterone secretion in lactating rats suggesting that HHA remains activated in lactation. To explore possible causes of this effect we studied the expression of thyroid receptors (TR), the long isoform of PRL receptor (PRLRl), members of the PRL signaling pathway, estradiol receptor (ER) and glucocorticoid receptor (GR) in HpC of Wistar female rats in different reproductive states (day 19 of gestation (G19), 2 (L2, early lactation) and 12 (L12) of lactation) in control (Co) and HyperT rats. Mild HyperT was induced with T4 (0.1 mg/kg/day, s.c.), a dose that allows the maintenance of lactation. HpC mRNA was obtained and the expression of receptors TRa1, TRa2, TRb1, TRb2, ERa, GR and PRLRl and members of the PRL signaling pathway (STAT5b, SOCS1 and SOCS3) was determined by RTqPCR. HpC mRNA content of TRs, STAT5b (activator of PRL signaling) and SOCS1 (supressor of PRL signaling) decreased from G19 to L12 in Co and HyperT rats (p<0.05). HyperT induced increases of TRa2 (P< 0.05 vs Co) and TRb2 in L2 (p< 0.01 vs. Co) without changes in others isoforms. HyperT increased STAT5b in G19 (p<0.05 vs. Co). ERa and PRLR mRNAs were unchanged by treatment or reproductive state while GR increased in L12 in both groups (p<0.05 vs. G19).These results indicate a physiological decline in HpC responsiveness to thyroid and PRL hormones in the transition from pregnancy to lactation in Co, while the increases observed in TRa2, TRb2 and STAT5b described in HyperT rats may be involved in the persistence of high HHA axis reactivity.Fil: Neira, Flavia Judith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Sánchez, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Pietrobon, Elisa Oliva. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Mackern Oberti, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Soaje, Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Jahn, Graciela Alma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Valdez, Susana Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaLXIV Reunión Anual de la Sociedad Argentina de Investigación Clínica; LI Reunión Anual de la Asociación Argentina de Farmacología Experimenta; XXI Reunión Anual de la Sociedad Argentina de Biología; XXXI Reunión Anual de la Sociedad Argentina de Protozoología; IX Reunión Anual de la Asociación Argentina de Nanomedicinas; VI Reunión Científica Regional de la Asociación Argentina de Ciencia y Tecnología de Animales de LaboratorioMar del PlataArgentinaSociedad Argentina de Investigación ClínicaAsociación Argentina de NanomedicinasAsociación Argentina de Farmacología ExperimentalSociedad Argentina de BiologíaSociedad Argentina de ProtozoologíaAsociación Argentina de Ciencia y Tecnología de Animales de Laboratori

Thyroid Hormone Controls Breast Cancer Cell Movement via Integrin αV/β3/SRC/FAK/PI3-Kinases

Thyroid hormones (TH) play a fundamental role in diverse processes, including cellular movement. Cell migration requires the integration of events that induce changes in cell structure towards the direction of migration. These actions are driven by actin remodeling and stabilized by the development of adhesion sites to extracellular matrix via transmembrane receptors linked to the actin cytoskeleton. Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that promotes cell migration and invasion through the control of focal adhesion turnover. In this work, we demonstrate that the thyroid hormone triiodothyronine (T3) regulates actin remodeling and cell movement in breast cancer T-47D cells through the recruitment of FAK. T3 controls FAK phosphorylation and translocation at sites where focal adhesion complexes are assembled. This process is triggered via rapid signaling to integrin αV/β3, Src, phosphatidylinositol 3-OH kinase (PI3K), and FAK. In addition, we established a cellular model with different concentration of T3 levels: normal, absence, and excess in T-47D breast cancer cells. We found that the expression of Src, FAK, and PI3K remained at normal levels in the excess of T3 model, while it was significantly reduced in the absence model. In conclusion, these results suggest a novel role for T3 as an important modulator of cell migration, providing a starting point for the development of new therapeutic strategies for breast cancer treatment.Fil: Flamini, Marina Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Uzair, Ivonne Denise. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Pennacchio, Gisela Erika. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Neira, Flavia Judith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Mondaca, Joselina Magali. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Cuello Carrión, Fernando Darío. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Jahn, Graciela Alma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Simoncini, Tommaso. Università degli Studi di Pisa; ItaliaFil: Sanchez, Angel Matias. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

Placental leukocyte infiltration accompanies gestational changes induced by hyperthyroidism

Thyroid dysfunctions lead to metabolic, angiogenic, and developmental alterations at the maternal–fetal interface that cause reproductive complications. Thyroid hormones (THs) act through their nuclear receptors that interact with other steroid hormone receptors. Currently, immunological regulation by thyroid status has been characterized to a far less extent. It is well known that THs exert regulatory function on immune cells and modulate cytokine expression, but how hyperthyroidism (hyper) modulates placental immunological aspects leading to placental alterations is unknown. This work aims to throw light on how hyper modulates immunological and morphological placental aspects. Control and hyper (induced by a daily s.c. injection of T4 0.25 mg/kg) Wistar rats were mated 8 days after starting T4 treatment and euthanized on days 19 (G19) and 20 (G20) of pregnancy. We removed the placenta to perform qPCR, flow cytometry, immunohistochemistry, Western blot and histological analysis, and amniotic fluid and serum to evaluate hormone levels. We observed that hyper increases the fetal number, fetal weight, and placental weight on G19. Moreover, hyper induced an endocrine imbalance with higher serum corticosterone and changed placental morphology, specifically the basal zone and decidua. These changes were accompanied by an increased mRNA expression of glucocorticoid receptor and monocyte chemoattractant protein-1, an increased mRNA and protein expression of prolactin receptor, and an increase in CD45+ infiltration. Finally, by in vitro assays, we evidenced that TH induced immune cell activation. In summary, we demonstrated that hyper modulates immunological and morphological placental aspects and induces fetal phenotypic changes, which could be related to preterm labor observed in hyper.Fil: Sánchez, María Belén. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad "Juan Agustín Maza"; Argentina. Universidad Nacional de Cuyo; ArgentinaFil: Neira, Flavia Judith. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo; Argentina. Universidad "Juan Agustín Maza"; ArgentinaFil: Moreno Sosa, María Tamara. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad "Juan Agustín Maza"; Argentina. Universidad Nacional de Cuyo; ArgentinaFil: Michel, María Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo; Argentina. Universidad "Juan Agustín Maza"; ArgentinaFil: Viruel, Luciana Belén. Universidad "Juan Agustín Maza"; ArgentinaFil: Germano, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo; ArgentinaFil: Pietrobon, Elisa Olivia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología; Argentina. Universidad Nacional de Cuyo; ArgentinaFil: Troncoso, Mariana Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo; ArgentinaFil: Soaje, Marta. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Fisiología; ArgentinaFil: Jahn, Graciela Alma. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo; ArgentinaFil: Valdez, Susana Ruth. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo; ArgentinaFil: Mackern Oberti, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Fisiología; Argentin