ABSTRACT
Resumen La aterosclerosis es una enfermedad que involucra múltiples mecanismos fisiopatológicos cuyo conocimiento no se ha dilucidado por completo. Con frecuencia, los avances científicos sobre la fisiopatología aterogénica generan que a diversas moléculas no consideradas previamente en el panorama de dicha enfermedad se les atribuyan acciones sobre el inicio o progresión de la misma. Un ejemplo representativo es el estudio de un nuevo mecanismo involucrado en el proceso aterogénico, consistente en la asociación entre el sistema de factores de crecimiento similares a la insulina (IGF) y la proteína plasmática A asociada al embarazo (PAPP-A). El sistema IGF es una familia de péptidos compuesto por 3 hormonas peptídicas, 4 receptores transmembranales y 6 proteínas transportadoras. El factor de crecimiento similar a la insulina tipo 1 (IGF-1) es el principal ligando del sistema IGF involucrado en la aterosclerosis coronaria y ejerce sus efectos mediante la activación del receptor IGF-1R en células de músculo liso vascular de las arterias coronarias o en macrófagos de placas ateroscleróticas. En células de músculo liso vascular promueve la migración y previene la apoptosis aumentando la estabilidad de la placa, y en macrófagos disminuye el transporte reverso de colesterol propiciando la formación de células espumosas. La regulación de la biodisponibilidad de IGF-1 en el endotelio se lleva a cabo por las proteasas de proteínas IGFBP, principalmente por la PAPP-A. En la presente revisión se abordan los mecanismos involucrados entre el sistema IGF y la PAPP-A en aterosclerosis coronaria con énfasis en los efectos moleculares producidos en células de músculo liso vascular y en macrófagos.
Abstract Atherosclerosis is a condition that involves multiple pathophysiological mechanisms and whose knowledge has not been fully elucidated. Often, scientific advances on the atherogenic pathophysiology generate that molecules not previously considered in the scene of this disease, were attributed actions on the onset or progression of it. A representative example is the study of a new mechanism involved in the atherogenic process, consisting of the association between the insulin-like growth factor (IGF) system and pregnancy-associated plasma protein-A (PAPP-A). Insulin-like growth factor system is a family of peptides that include 3 peptide hormones, 4 transmembrane receptors and 6 binding proteins. Insulin-like growth factor-1 (IGF-1) is the main ligand of the IGF system involved in coronary atherosclerosis. IGF-1 exerts its effects via activation of the IGF-1R receptor on vascular smooth muscle cells or macrophages. In vascular smooth muscle cells promotes migration and prevents apoptosis which increases plaque stability while in macrophages reduces reverse cholesterol transport leading to the formation of foam cells. Regulation of IGF-1 endothelial bioavailability is carried out by IGFBP proteases, mainly by PAPP-A. In this review, we address the mechanisms between IGF system and PAPP-A in atherosclerosis with emphasis on molecular effects on vascular smooth muscle cells and macrophages.
Subject(s)
Humans , Animals , Pregnancy-Associated Plasma Protein-A/physiology , Coronary Artery Disease/etiology , Insulin-Like Growth Factor I/physiologyABSTRACT
La enfermedad quística ovárica (COD) es una de las principales causas de falla reproductiva y de infertilidad, y constituye uno de los de los trastornos reproductivos más frecuentes en vacas lecheras de alta producción. El desarrollo de esta enfermedad está asociado a un desequilibrio en el eje hipotalámico-hipofisario-gonadal en el cual factores endocrinos, entre ellos el sistema de factores de crecimiento análogos a insulina (IGF), participan en el desarrollo folicular, diferenciación celular y la secreción de hormonas ováricas. Considerando al sistema IGF como un importante regulador del crecimiento y funcionalidad folicular, evaluamos la participación de componentes del sistema IGF en el desarrollo de la COD. Las alteraciones en diferentes componentes del sistema IGF que podrían afectar al normal funcionamiento del ovario participando en el desarrollo de la COD en bovinos.
Cystic ovarian disease (COD) is one of the most frequent reproductive disorders in dairy cows. Their development is associated with an imbalance in the hypothalamus-hypophyseal-gonadal axis in which endocrine factors, including insulin like growth factor (IGF) system, are involved in follicular development, cell differentiation and secretion ovarian hormones. Considering that the IGF system is an important regulator of the follicular growth and functionality, we have evaluated the involvement of members of the IGF system in the COD development. Alterations in different components of the IGF system could modify the normal ovarian function and participate in the development of the COD in cattle.
ABSTRACT
OBJECTIVE: To investigate the influence of tumor necrosis factor (TNF)-alpha on the expression of insulin-like growth factor (IGF)-II, insulin-like growth factor binding protein (IGFBP)-1, 2, 3, and 5 mRNA in cultured human luteinized granulosa cells. METHODS: Human luteinized granulosa cells were obtained from the follicular fluid by transvaginal oocyte aspiration from infertile patients undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). The cells were cultured for 72 hours with TNF-alpha at concentrations of 1.0, 10.0, and 100.0 ng/mL, respectively. The cells not treated with TNF-alpha were served as control. Riverse transcription-polymerase chain reaction (RT-PCR) had been used to examine the expression of IGF-II, IGFBP-1, 2, 3, and 5 mRNA. Results were analyzed with Kolmogorov-Smirnov test and analysis of variance (ANOVA) and statical significance was defined as p<0.05. RESULTS: The expressions of IGF-II mRNA in 10.0 and 100.0 ng/mL of TNF-alpha groups were significantly lower than the control group (p<0.05, p<0.05, respectively). The expressions of IGFBP-2 mRNA were seemed to be decreased in 10.0 and 100.0 ng/mL of TNF-alpha groups than the control group (p=0.05, p=0.06, respectively). The expression of IGFBP-3 mRNA was seemed to be increased in 100.0 ng/mL of TNF-alpha group than the control group (p=0.08). There were no statistically significant differences in the expressions of IGFBP-1 and 5 in all groups. CONCLUSION: TNF-alpha might play a role as a regulator of human ovarian physiology by modulating the expression of IGF-II in luteinized granulosa cells.
Subject(s)
Female , Humans , Carrier Proteins , Fertilization in Vitro , Follicular Fluid , Granulosa Cells , Insulin-Like Growth Factor Binding Protein 1 , Insulin-Like Growth Factor Binding Protein 2 , Insulin-Like Growth Factor Binding Protein 3 , Insulin-Like Growth Factor II , Lutein , Oocyte Retrieval , Physiology , Rivers , RNA, Messenger , Tumor Necrosis Factor-alphaABSTRACT
OBJECTIVE: To investigate the influence of activin and follistatin on the expression of IGF (insulin-like growth factor)-I, II, IGFBP (insulin-like growth factor binding protein)-1, 2, and 3 mRNA in cultured mouse granulosa cells MATERIALS AND METHODS: The granulosa cells were obtained from the mouse and cultured for 6 days with 10 ng/ml of activin, 10 ng/ml of follistatin, and 10 ng/ml of activin with 10 ng/m of follistatin, respectively. The cells not treated with activin or follistatin served as control. Reverse transcription-polymerase chain reaction (RT-PCR) has been used to examine the expression of IGF-I, II, IGFBP-1, 2, and 3 mRNA. Results were analyzed with Kolmogorov-Smirnov test and analysis of variance (ANOVA) and statistical significance was defined as p<0.05. RESULTS: The expression of IGF-I and II mRNA were not different significantly. However, the expression of IGFBP-3 mRNA was significantly increased in the follistatin group compared to the control group (p<0.05) and significantly decreased in the activin with follistatin group compared to the control group (p<0.05). The expression of IGFBP-1 mRNA was seemed to be increased in the activin group and decreased in the follistatin group compared to the control group, respectively (p=0.07, p=0.07). The expression of IGFBP-2 and 3 mRNA were seemed to be decreased in the activin group compared to the control group (p=0.06, p=0.07, respectively). CONCLUSION: Activin and follistatin might play a role as regulators of mouse ovarian physiology by modulating the IGF system, especially IGFBPs.
Subject(s)
Animals , Female , Mice , Activins , Carrier Proteins , Follistatin , Granulosa Cells , Insulin-Like Growth Factor Binding Protein 1 , Insulin-Like Growth Factor Binding Protein 2 , Insulin-Like Growth Factor Binding Protein 3 , Insulin-Like Growth Factor Binding Proteins , Insulin-Like Growth Factor I , Physiology , RNA, MessengerABSTRACT
OBJECTIVES: To investigate the influence of TNF-alpha on the secretion of estradiol (E2), progesterone (P4), insulin-like growth factor (IGF)-II, insulin-like growth factor binding protein (IGFBP)-1, 2, and 3 in cultured human luteinized granulosa cells MATERIALS AND METHODS: Human luteinized granulosa cells were obtained from the follicular fluid by transvaginal oocyte aspiration from infertile patients undergoing controlled ovarian hyperstimulation (COH) for in vitro fertilization (IVF). The cells were grouped into the control, 1.0, 10.0, and 100.0 ng/ml of TNF-alpha group according to the concentrations of TNF-alpha. The cells were cultured for 72 hours with the different concentrations of TNF-alpha as descibed above. The cells not treated with TNF-alpha served as control. The concentrations of E2, P4, IGF-I, IGFBP-1, 2, and 3 were determined in conditioned culture media by immunoradiometric assay (IRMA) or radioimmunoassay (RIA). RESULTS: The cell number in 100.0 ng/ml of TNF-alpha group was significantly higher than those in other groups, although the cell viabilities were similar in all groups. There were no statistically significant differences in the concentrations of E2 in all groups. However, the concentrations of P4 were seemed to be decreased as the concentrations of TNF-alpha were increased and the concentration of P4 in 100.0 ng/ml of TNF-alpha group was significantly lower than those in the control and other TNF-alpha groups. The concentrations of IGF-II, IGFBP-1, 2, and 3 were not different among the control and each TNF-alpha group. The secretion of E2 and P4 was not affected by IGF type I receptor antibody pretreatment. CONCLUSION: TNF-alpha might play a role as a regulator of ovarian physiology by modulating luteinized granulosa cellular proliferation and P4 secretion, and this mechanism might not be related to IGF system.