Impact of Neonatal Manipulation of Androgen Receptor Function on Endocrine-Metabolic Programming in the Juvenile Female Rat

The impact of neonatal androgen receptor (AR) stimulation/blockage, due to testosterone propionate (TP)/AR antagonist treatment, on individual anthropometry and neuroendocrine-metabolic function was evaluated in the juvenile female rat. Pups (age 5 days) were s.c. injected with TP (1.25 mg), flutamide (F; 1.75 mg), and TP + F or vehicle (control, CT) and studied on day 30 of age. Body weight (BW), parametrial adipose tissue (PMAT) mass, food intake, adipoinsular axis, and steroidogenic functions were examined. Opposite to TP-rats, F-treated rats developed hypophagia, grew slowly (BW and PMAT), and displayed heightened peripheral insulin sensitivity. These F effects were abrogated in TP + F animals. Accordingly, TP rats displayed hyperleptinemia, an effect fully prevented by F cotreatment. Finally, androgen-treated animals bore an irreversible ovarian dysfunction (reduced circulating levels of 17HOP4 and ovary 17HOP4 content and P450c17 mRNA abundance). These data indicate that early stimulation of AR enhanced energy store, blockage of AR activity resulted in some beneficial metabolic effects, and neonatally androgenized rats developed a severe ovarian dysfunction. Our study highlights the important role of AR in the early organizational programming of metabolic and neuroendocrine functions.Fil: Ongaro, Luisina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Giovambattista, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; ArgentinaFil: Spinedi, Eduardo Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto Multidisciplinario de Biología Celular. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas. Instituto Multidisciplinario de Biología Celular. Universidad Nacional de La Plata. Instituto Multidisciplinario de Biología Celular; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - la Plata. Centro de Endocrinología Experimental y Aplicada. Universidad Nacional de la Plata. Facultad de Cs.médicas. Centro de Endocrinología Experimental y Aplicada; Argentin

Química: ¿Cuáles son las condiciones que permiten la vida en la Tierra? : Propuesta de aulas heterogéneas desde la enseñanza para la comprensión

La presente actividad tiene como marco de referencia la Enseñanza para la Comprensión (EPC). Basado en este modelo pedagógico, se propone un enfoque del diseño didáctico que hace especial énfasis en la búsqueda de comprensiones duraderas, flexibles y profundas. Tal como lo plantea Perkins (1995), la comprensión no es algo que se posea, sino que se construye, y se encuentra siempre en estado de formación. Cuando comprendemos un tema o concepto, no sólo hemos recibido la información sino que también somos capaces de utilizarla para realizar diversos desempeños. Las actividades de comprensión implican diversos desafíos cognitivos a los que se enfrenta cada alumno según sus particulares habilidades de compresión.Colegio Nacional "Rafael Hernández

Modificación neonatal de la actividad andrógenica: impacto sobre la programación endocrino-metabólica en la rata hembra

El objetivo general de este estudio es avanzar en el esclarecimiento de mecanismos fisiopatológicos responsables del desarrollo de cambios en el metabolismo y la función esteroidogénica adrenal y ovárica como consecuencia de una modificación de la acción androgénica, ya sea por una hiperandrogenemia temprana como por un bloqueo de los receptores de andrógeno a edad neonatal. Está postulado que la androgenización pre-o neonatal en el sexo femenino interaccionaría con factores genéticos, el medio ambiente (dieta, etc.) o la combinación de ellos, afectándose la programación en la diferenciación de tejidos blanco para andrógenos y modificando la insulino-sensibilidad durante la edad reproductiva. Sin embargo, aún no existe consenso internacional sobre los mecanismos involucrados en las alteraciones inducidas por el temprano exceso androgénico, se infiere que las modificaciones estarían vinculadas a la producción adrenal/ovárica de andrógenos, y las modificaciones endócrinas adipocitarias que puedan afectar el estado metabólico del individuo. Estos estudios podrían aportar al esclarecimiento del desarrollo de insulino-resistencia y la contribución androgénica al desarrollo sexual de la rata hembra, dependientes de una temprana alteración de la actividad de los esteroides sexuales. (Párrafo extraído del texto a modo de resumen)Facultad de Ciencias Exacta

Impact of Neonatal Manipulation of Androgen Receptor Function on Endocrine-Metabolic Programming in the Juvenile Female Rat

The impact of neonatal androgen receptor (AR) stimulation/blockage, due to testosterone propionate (TP)/AR antagonist treatment, on individual anthropometry and neuroendocrine-metabolic function was evaluated in the juvenile female rat. Pups (age 5 days) were s.c. injected with TP (1.25 mg), flutamide (F; 1.75 mg), and TP + F or vehicle (control, CT) and studied on day 30 of age. Body weight (BW), parametrial adipose tissue (PMAT) mass, food intake, adipoinsular axis, and steroidogenic functions were examined. Opposite to TP-rats, F-treated rats developed hypophagia, grew slowly (BW and PMAT), and displayed heightened peripheral insulin sensitivity. These F effects were abrogated in TP + F animals. Accordingly, TP rats displayed hyperleptinemia, an effect fully prevented by F cotreatment. Finally, androgen-treated animals bore an irreversible ovarian dysfunction (reduced circulating levels of 17HOP4 and ovary 17HOP4 content and P450c17 mRNA abundance). These data indicate that early stimulation of AR enhanced energy store, blockage of AR activity resulted in some beneficial metabolic effects, and neonatally androgenized rats developed a severe ovarian dysfunction. Our study highlights the important role of AR in the early organizational programming of metabolic and neuroendocrine functions.Instituto Multidisciplinario de Biología CelularCentro de Endocrinología Experimental y Aplicad

Dietary and Hormonal Factors Involved in Healthy or Unhealthy Visceral Adipose Tissue Expansion

White adipose tissue (WAT) expansion is related to the development of metabolic disorders found in obesity. WAT expansion is the result of generation of new adipose cells by activation of adipogenesis and/or the increase in adipose cell size (hypertrophy). The balance between these two processes determines whether WAT expansion occurs predominantly by hyperplasia, which means the increase in the number of adipocytes, or hypertrophy. Hypertrophic adipocytes are characterized by changes in adipokine secretion pattern, insulin resistance and altered lipid metabolism, which is the reason why WAT-hypertrophic expansion is considered unhealthy. Conversely, the generation of new mature adipocytes by adipogenesis contributes to reduction of the development of hypertrophic adipocytes and therefore maintain normal WAT functions, leading to healthy hyperplastic expansion. The adipogenic capacity of adipose tissue depends on the adipogenic potential and the number of adipocyte precursor cells. Different factors are known to regulate adipogenic process and adipose tissue function, contributing to a healthy or unhealthy expansion that occurs under positive energy balance. This chapter discusses the role of fructose intake and glucocorticoids and testosterone as regulators of adipose tissue function and expansion

Oral metformin treatment counteracts Adipoinsular Axis Dysfunction in hypothalamic obese rats

Rats neonatally treated with monosodium L-glutamate (MSG) are deeply dysfunctional in adulthood. We explored the effect of an oral low dose of metformin treatment in male MSG rats on adipoinsular axis and visceral adipose tissue (VAT) dysfunctions, in both basal (nonfasting) and endotoxemia conditions. MSG rats, treated or not treated with metformin (30 days prior to experimentation), and control litter-mates (CTR) were studied at 90 days of age. Peripheral concentrations of glucose, lipids, and hormones were determined in basal and post-lipopolysaccharide (LPS) treatment conditions. Food intake and body weight (BW) were recorded and VAT mass and leptin mRNA levels were evaluated. Data indicated that MSG rats were lighter and displayed hypercorticosteronemia, hypophagia, adipoinsular axis hyperactivity, and enhanced VAT mass associated with an increased leptin gene expression. Interestingly, metformin-treated MSG rats corrected BW catch-up and counteracted VAT (mass and leptin mRNA level) and adipoinsular axis (basal and post-LPS) dysfunctions. Thus metformin treatment in MSG rats is able to correct several VAT and metabolic-endocrine dysfunctions. Our study suggests that a low-dose metformin therapy is effective to correct, at least in part, adipoinsular axis dysfunction in hypertrophic obese phenotypes, such as that of the human Cushing syndrome.Fil: Castrogiovanni, Daniel Cayetano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto Multidisciplinario de Biología Celular (i); ArgentinaFil: Ongaro, Luisina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto Multidisciplinario de Biología Celular (i); ArgentinaFil: Zubiría, María Guillermina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto Multidisciplinario de Biología Celular (i); ArgentinaFil: Giovambattista, Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico la Plata. Instituto Multidisciplinario de Biología Celular (i); ArgentinaFil: Spinedi, Eduardo Julio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Cientifico Tecnológico la Plata. Centro de Endocrinologia Experimental y Aplicada (i); Argentina. Universidad Nacional de La Plata; Argentin

Oral Metformin Treatment Counteracts Adipoinsular Axis Dysfunction in Hypothalamic Obese Rats

Rats neonatally treated withmonosodiumL-glutamate (MSG) are deeply dysfunctional in adulthood. We explored the effect of an oral low dose of metformin treatment in male MSG rats on adipoinsular axis and visceral adipose tissue (VAT) dysfunctions, in both basal (nonfasting) and endotoxemia conditions. MSG rats, treated or not treated with metformin (30 days prior to experimentation), and control litter-mates (CTR) were studied at 90 days of age. Peripheral concentrations of glucose, lipids, and hormones were determined in basal and post-lipopolysaccharide (LPS) treatment conditions. Food intake and body weight (BW) were recorded and VAT mass and leptin mRNA levels were evaluated. Data indicated that MSG rats were lighter and displayed hypercorticosteronemia, hypophagia, adipoinsular axis hyperactivity, and enhanced VAT mass associated with an increased leptin gene expression. Interestingly,metformin-treatedMSG rats corrected BWcatch-up and counteracted VAT (mass and leptinmRNA level) and adipoinsular axis (basal and post-LPS) dysfunctions. Thus metformin treatment in MSG rats is able to correct several VAT and metabolic-endocrine dysfunctions. Our study suggests that a low-dose metformin therapy is effective to correct, at least in part, adipoinsular axis dysfunction in hypertrophic obese phenotypes, such as that of the human Cushing syndrome.Facultad de Ciencias Médica

Fructose rich diet-induced high plasminogen activator inhibitor-1 (PAI-1) production in the adult female rat: Protective effect of progesterone

The effect of progesterone (P4) on fructose rich diet (FRD) intake-induced metabolic, endocrine and parametrial adipose tissue (PMAT) dysfunctions was studied in the adult female rat. Sixty day-old rats were i.m. treated with oil alone (control, CT) or containing P4 (12 mg/kg). Rats ate Purina chow-diet ad libitum throughout the entire experiment and, between 100 and 120 days of age drank ad libitum tap water alone (normal diet; CT-ND and P4-ND) or containing fructose (10% w/v; CT-FRD and P4-FRD). At age 120 days, animals were subjected to a glucose tolerance test or decapitated. Plasma concentrations of various biomarkers and PMAT gene abundance were monitored. P4-ND (vs. CT-ND) rats showed elevated circulating levels of lipids. CT-FRD rats displayed high (vs. CT-ND) plasma concentrations of lipids, leptin, adiponectin and plasminogen activator inhibitor-1 (PAI-1). Lipidemia and adiponectinemia were high (vs. P4-ND) in P4-FRD rats. Although P4 failed to prevent FRD-induced hyperleptinemia, it was fully protective on FRD-enhanced plasma PAI-1 levels. PMAT leptin and adiponectin mRNAs were high in CT-FRD and P4-FRD rats. While FRD enhanced PMAT PAI-1 mRNA abundance in CT rats, this effect was absent in P4 rats. Our study supports that a preceding P4-enriched milieu prevented the enhanced prothrombotic risk induced by FRD-elicited high PAI-1 production.Instituto Multidisciplinario de Biología CelularFacultad de Ciencias MédicasFacultad de Ciencias Exacta

Dietary and Hormonal Factors Involved in Healthy or Unhealthy Visceral Adipose Tissue Expansion

White adipose tissue (WAT) expansion is related to the development of metabolic disorders found in obesity. WAT expansion is the result of generation of new adipose cells by activation of adipogenesis and/or the increase in adipose cell size (hypertrophy). The balance between these two processes determines whether WAT expansion occurs predominantly by hyperplasia, which means the increase in the number of adipocytes, or hypertrophy. Hypertrophic adipocytes are characterized by changes in adipokine secretion pattern, insulin resistance and altered lipid metabolism, which is the reason why WAT-hypertrophic expansion is considered unhealthy. Conversely, the generation of new mature adipocytes by adipogenesis contributes to reduction of the development of hypertrophic adipocytes and therefore maintain normal WAT functions, leading to healthy hyperplastic expansion. The adipogenic capacity of adipose tissue depends on the adipogenic potential and the number of adipocyte precursor cells. Different factors are known to regulate adipogenic process and adipose tissue function, contributing to a healthy or unhealthy expansion that occurs under positive energy balance. This chapter discusses the role of fructose intake and glucocorticoids and testosterone as regulators of adipose tissue function and expansion.Facultad de Ciencias Médica

Fructose rich diet-induced high plasminogen activator inhibitor-1 (PAI-1) production in the adult female rat: Protective effect of progesterone

The effect of progesterone (P4) on fructose rich diet (FRD) intake-induced metabolic, endocrine and parametrial adipose tissue (PMAT) dysfunctions was studied in the adult female rat. Sixty day-old rats were i.m. treated with oil alone (control, CT) or containing P4 (12 mg/kg). Rats ate Purina chow-diet ad libitum throughout the entire experiment and, between 100 and 120 days of age drank ad libitum tap water alone (normal diet; CT-ND and P4-ND) or containing fructose (10% w/v; CT-FRD and P4-FRD). At age 120 days, animals were subjected to a glucose tolerance test or decapitated. Plasma concentrations of various biomarkers and PMAT gene abundance were monitored. P4-ND (vs. CT-ND) rats showed elevated circulating levels of lipids. CT-FRD rats displayed high (vs. CT-ND) plasma concentrations of lipids, leptin, adiponectin and plasminogen activator inhibitor-1 (PAI-1). Lipidemia and adiponectinemia were high (vs. P4-ND) in P4-FRD rats. Although P4 failed to prevent FRD-induced hyperleptinemia, it was fully protective on FRD-enhanced plasma PAI-1 levels. PMAT leptin and adiponectin mRNAs were high in CT-FRD and P4-FRD rats. While FRD enhanced PMAT PAI-1 mRNA abundance in CT rats, this effect was absent in P4 rats. Our study supports that a preceding P4-enriched milieu prevented the enhanced prothrombotic risk induced by FRD-elicited high PAI-1 production.Instituto Multidisciplinario de Biología CelularFacultad de Ciencias MédicasFacultad de Ciencias Exacta