RESUMO
The actions of mammalian insulin-like growth factors (IGF-I and IGF-II) and insulin on skeletal growth of the axolotl, Ambystoma mexicanum, were examined by monitoring the in vitro uptake of [35S]sulfate by cartilage. Both growth factors stimulated sulfate uptake significantly at a concentration of 13 nM. The increase after incubation with 130 nM insulin was similar (uptake ca. 160% of control), but the effect was not significant. Further, the binding of 125I-IGF-I and 125I-IGF-II was studied in the skeletal tissue by quantitative in vitro autoradiography. Specific binding sites for both growth factors were localized in the perichondrial tissue. 125I-IGF-II binding sites were saturated at the used doses. Scatchard and Hill plots demonstrate heterogeneous binding sites exhibiting positive cooperativity. IGF-II was more effective than IGF-I in competitively displacing both labeled ligands. Insulin only slightly affected the binding at the highest concentrations. These results indicate that the insulinlike growth factors regulate skeletal growth in urodeles as in mammals.
Assuntos
Ambystoma mexicanum/metabolismo , Cartilagem/metabolismo , Hipoglicemiantes/farmacologia , Insulina/farmacologia , Somatomedinas/farmacologia , Sulfatos/farmacocinética , Animais , Autorradiografia , Sítios de Ligação , Cartilagem/efeitos dos fármacos , Cartilagem/crescimento & desenvolvimento , Técnicas In Vitro , Radioisótopos de Enxofre/farmacocinéticaRESUMO
El hiperandrogenismo ovárico funcional es un trastorno de alta prevalencia en las mujeres de edad fértil; más del 30 por ciento de ellas presenta insulinorresistencia (IR). Estas pacientes están expuestas a desarrollar una diabetes no insulinodependiente (DMNID) a edades más tempranas que en la población general. La etiología de la insulinorresistencia asociada a hiperandrogenemia es parcialmente conocida. Se ha observado que la insulina en altas concentraciones estimula la producción de andrógenos en la teca y el estroma de ovarios obtenidos de mujeres con insulinorresistencia e hiperandrogenismo. Se postula, por lo tanto, que sería la insulinorresistencia la que al condicionar una hiperinsulinemia llevaría a una hiperandrogenemia a través del efecto estimulador de la insulina sobre las células tecales del ovario vía receptor de IGF-I. Además la insulina reduce la SHBG aumentando la fracción libre de andrógeno y disminuye la IGFBP-I, lo que aumenta el efecto de IGF-I sobre el ovario. Debido a que los andrógenos son atretogénicos, la insulina favorece la atresia folicular y la mayor secreción de andrógenos por el ovario lo que tiene como consecuencia una disminución de la producción de estrógenos, lo que crea un desbalance en favor de los andrógenos
Assuntos
Humanos , Feminino , Hiperandrogenismo/complicações , Resistência à Insulina/fisiologia , Androgênios , Insulina/farmacologia , Ovário/citologia , Ovário/fisiologia , Ovário/metabolismo , Receptor de Insulina , Síndrome de Hiperestimulação Ovariana/etiologia , Somatomedinas/farmacologia , Células TecaisRESUMO
Receptors for insulin and insulin-like growth factor-1 (IGF-1) have been demonstrated on activated T-lymphocytes. The question is whether receptors for insulin or IGF-1 have any function in these cells. In this study we demonstrate that the concentration of IGF-1 in commercial samples of fetal calf serum is about 70 times that of insulin. Moreover, antibodies binding IGF-1 reduce responses of human peripheral blood mononuclear cells to PHA by about 50%, whereas antibodies to insulin have no demonstrable effect. These observations suggest that binding of IGF-1 to specific receptors contributes to the proliferative responses of activated T-lymphocytes.
Assuntos
Fator de Crescimento Insulin-Like I/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Fito-Hemaglutininas/farmacologia , Somatomedinas/farmacologia , Linfócitos T/efeitos dos fármacos , Animais , Anticorpos/imunologia , Bovinos/sangue , Divisão Celular/efeitos dos fármacos , Sangue Fetal/fisiologia , Humanos , Fator de Crescimento Insulin-Like I/imunologia , Fator de Crescimento Insulin-Like I/isolamento & purificação , Receptores de Superfície Celular/fisiologia , Receptores de Somatomedina , Proteínas Recombinantes/farmacologia , Estimulação Química , Linfócitos T/citologiaRESUMO
The growth regulation of cultured mouse fibroblasts and functional adrenal cells was studied. Variants of mutants from these cell lines were obtained. The effects of classical hormones (insulin, hydrocortisone and adrenocorticotropin) and of growth factors (EGF and PF) were analysed. These hormones stimulate or inhibit the entry of cells into S phase. However G1 cells become irreversibly committed to DNA synthesis 5 hours before entering S phase.
Assuntos
Ciclo Celular/efeitos dos fármacos , Replicação do DNA/efeitos dos fármacos , Substâncias de Crescimento/farmacologia , Hormônios/farmacologia , Glândulas Suprarrenais/citologia , Animais , Células Cultivadas , Fator de Crescimento Epidérmico/farmacologia , Fibroblastos , Hidrocortisona/farmacologia , Insulina/farmacologia , Interfase/efeitos dos fármacos , Camundongos , Mutação , Prostaglandinas F/farmacologia , Somatomedinas/farmacologia , Fatores de TempoRESUMO
Suppression of growth without significant alterations in hormonal patterns has been demonstrated for the neurostimulant drug pemoline. Comparison of the in vitro effect of pemoline, methylphenidate, and methamphetamine on somatomedin-stimulated sulfate uptake by cartilage showed all three drugs to be inhibitory. Sulfate uptake by cartilage can be directly related to growth and glycosaminoglycan biosynthesis. Assay of two of the enzymes involved in the glycosaminoglycan biosynthetic pathway showed that methamphetamine and methylphenidate caused a marked depression of xylosyl- and galactosyltransferase enzyme activity. These data suggest an interference with cartilage metabolism as one possible mechanism for the growth retardation observed in children on neurostimulant drug therapy.