ABSTRACT
ABSTRACT Objective: To present a case of bilateral gynecomastia in a prepubertal boy with autism spectrum disorder, diagnosed with myotonic dystrophy type 1. Case description: A 12-year-old boy with autism spectrum disorder presented at a follow-up visit with bilateral breast growth. There was a family history of gynecomastia, cataracts at a young age, puberty delay, and myotonic dystrophy type 1. The physical examination showed that he had bilateral gynecomastia with external genitalia Tanner stage 1. Neurologic examination was regular, without demonstrable myotonia. The analytical study revealed increased estradiol levels and estradiol/testosterone ratio. After excluding endocrine diseases, the molecular study of the dystrophia myotonica protein kinase gene confirmed the diagnosis of myotonic dystrophy type 1. Comments: A diagnosis of prepubertal gynecomastia should include an investigation for possible underlying diseases. This case report highlights the importance of considering the diagnosis of myotonic dystrophy type 1 in the presence of endocrine and neurodevelopmental manifestations.
RESUMO Objetivo: Apresentar o caso de um adolescente pré-púbere com ginecomastia bilateral e transtorno do espectro autista, diagnosticado com distrofia miotônica tipo 1. Descrição do caso: Adolescente do sexo masculino de 12 anos, com transtorno do espectro autista, observado em consulta de seguimento por crescimento mamário bilateral. O paciente tinha antecedentes familiares de ginecomastia, catarata em idade jovem, atraso pubertário e distrofia miotônica tipo 1. À observação física, apresentava ginecomastia bilateral estádio 1 de Tanner. O exame neurológico era normal, sem miotonia aparente. O estudo analítico mostrou níveis elevados de estradiol e da relação estradiol/testosterona. Após exclusão de causas endócrinas, o estudo molecular do gene DMPK confirmou o diagnóstico de distrofia miotônica tipo 1. Comentários: Perante um quadro de ginecomastia pré-púbere, deve-se excluir doenças subjacentes. Este caso reforça a importância de considerar o diagnóstico de distrofia miotônica tipo 1 na presença de manifestações endócrinas e do neurodesenvolvimento.
Subject(s)
Humans , Male , Child , Gynecomastia/etiology , Myotonic Dystrophy/complications , Pedigree , Testosterone/blood , Puberty , Estradiol/chemistry , Myotonin-Protein Kinase/genetics , Autism Spectrum Disorder , Genitalia, Male/anatomy & histology , Gynecomastia/blood , Myotonic Dystrophy/diagnosis , Myotonic Dystrophy/genetics , Myotonic Dystrophy/bloodABSTRACT
Molecular docking has been used to compare and contrast the binding modes of oestradiol with the wild-type and some disease-associated mutant forms of the human CYP1b1 protein.The receptor structures used for docking were derived from molecular dynamics simulations of homology-modelled structures. Earlier studies involving molecular dynamics and principal component analysis indicated that mutations could have a disruptive effect on function,by destabilizing the native properties of the functionally important regions, especially those of the haem-binding and substrate-binding regions,which constitute the site of catalytic activity of the enzyme.In order to gain more insights into the possible differences in substrate-binding and catalysis between the wild-type and mutant proteins,molecular docking studies were carried out. Mutants showed altered protein -ligand interactions compared with the wild-type as a consequence of changes in the geometry of the substrate-binding region and in the position of haem relative to the active site. An important difference in ligand -protein interactions between the wild-type and mutants is the presence of stacking interaction with phenyl residues in the wild-type,which is either completely absent or considerably weaker in mutants.The present study revealed essential differences in the interactions between ligand and protein in wild-type and disease mutants,and helped in understanding the deleterious nature of disease mutations at the level of molecular function.
Subject(s)
Cytochrome P-450 Enzyme System/metabolism , Estradiol/chemistry , Glaucoma/congenital , Humans , Models, Chemical , Molecular Structure , Mutation , Protein BindingABSTRACT
Es conocido que las hormonas esteroideas sexuales modulan la composición corporal y otras funciones endocrinas. El objetivo del presente trabajo fue estudiar el impacto de la administración de esteroides sexuales sobre la insulinosensibilidad periférica y la función secretora adipocitaria. Grupos de ratas hembra recibieron vehículo (C) o valerato de E2 o propionato de T. Se monitoreó el peso corporal y la ingesta de alimento hasta el día experimental, que fueron sacrificados en condición basal o sometidos a un test de sobrecarga con glucosa. Se evaluaron las concentraciones de leptina, E2, T, glucosa, triglicéridos e insulina (INS). Se ponderó el tejido adiposo parametrial y se aislaron los adipocitos e incubaron con o sin INS. E2 indujo una temprana (p < 0,05) hipofagia, contrariamente, T indujo una moderada (p < 0,05) hiperfagia. Los animales E2 resultaron con menor peso y masa adiposa parametrial que los C (p < 0,05). Los niveles plasmáticos no se modificaron en los animales E2 ni T, salvo el desarrollo de hiperleptinemia en el grupo E2 (p < 0,05). El test de tolerancia a la glucosa mostró (p < 0,05) aumento y disminución en la insulinosensibildad en los animales E2 y T, respectivamente. Finalmente, los adipocitos aislados de animales E2 como los T desarrollaron una disminuida (p < 0,05 vs. C) respuesta a INS. Nuestro estudio pone en evidencia los efectos de E2 y T sobre la sensibilidad a insulina y la función adipocitaria.
Sex hormones are known to modulate body composition and endocrine functions. The aim of the present study was to analyze the impact of sexual steroids administration on the outlying insulin-sensibility and adipocyte secretory function. Groups of female rats received either vehicle (C), E2 valerate, or T propionate. Daily food intake and body weight were recorded until sacrifice under basal conditions or after high glucose load test. Plasma concentrations of leptin, E2, T, glucose, triglycerides, and insulin (INS) were evaluated. The parametrial adipose tissue was pondered and adipocytes were isolated and then incubated with or without INS. E2 induced early hypophagia (p< 0,05); contrarily, T induced moderate hyperphagia (p<0,05). Weight and fatty parametrial mass values were lower for E2- than C-treated animals (p<0,05). Plasma levels remained unmodified either for E2 or T groups, though E2 animals developed hyperleptinemia (p<0.05). The high glucose load test showed increased and decreased insulin-sensitivity (p<0.05) in E2 and T groups, respectively. Finally, E2 and T isolated adipocytes were less sensitive to insulin-induced leptin secretion than C cells (p<0.05 vs. C). Our study reveals that E2 and T hormones affect sensibility to insulin as well as adipocyte functions.
Subject(s)
Animals , Female , Rats , Gonadal Steroid Hormones/adverse effects , Gonadal Steroid Hormones/metabolism , Adipocytes/physiology , Insulins/physiology , Body Composition/physiology , Leptin/biosynthesis , Estradiol/chemistry , Endocrine Cells/physiologyABSTRACT
El objetivo del estudio fue evaluar si la relación molecular preovulatoria entre la progesterona y el estradiol tiene cambios dependientes de la edad en pacientes sometidas a hiperestimulación ovárica controlada. Fueron evaluados 180 ciclos de fertilización in vitro convencional. Las pacientes se dividieron en tres grupos: Grupo 1 (pacientes menores de 30 años; n=40), grupo 2 (edad entre 30 y 35 años, n=82), y grupo 3 (edad entre 36 y 40 años; n=58). Se usó supresión hipofisaria con acetato de leuprolide en todos los casos. La relación molecular progesterona/estradiol se determinó con la siguiente fórmula: [Concentración sérica de progesterona (ng/mL) x 3180 (SI x 103) ÷ concentración sérica de estradiol (pg/ml) x 3.671(SI)]. En pacientes mayores de 38.5 años hubo correlación positiva entre el estradiol y la progesterona preovulatorios (R=0.55, R2=0.30) Hubo diferencia significativa en la relación molecular entre el grupo 1 y 2 (P < 0.001), entre el grupo 1 y el 3 (P< 0.0001), así como entre el grupo 1 y los grupos 2 y 3 tomados en conjunto (P < 0.0001). Se concluye que la relación molecular preovulatoria entre progesterona y estradiol disminuye con la edad aun cuando no haya otras evidencias de disminución de la función ovárica. En este trabajo se discute la posibi-lidad de usar este fenómeno para evaluar la función ovárica.