Adrenarca y función Hipotálamo-Hipófiso-Gonadal (HHG) en pacientes nacidos pequeños para edad gestacional (PEG) en función de la caracterización molecular del gen del Receptor de Hormona de Crecimiento (GHRd3/d3, GHRd3/fl, GHRfl/fl) en población Argentina
The Growth Hormone Receptor (GHR) mediates the action of Growth Hormone (GH) on growth and metabolism. In humans, GH is secreted by the pituitary gland and acts directly on the GHR in various cell types, generating an increase in the expression of the Insulin Like Growth Factor-1 (IGF1) as well as o...
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Facultad de Farmacia y Bioquímica
2019
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_3168 http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_3168.dir/3168.PDF |
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I28-R145-HWA_3168 |
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dspace |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-145 |
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Repositorio Digital de la Universidad de Buenos Aires (UBA) |
| language |
Español |
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spa |
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Hormona Crecimiento Receptor PEG Ciencias de la vida |
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Hormona Crecimiento Receptor PEG Ciencias de la vida Pujana Pentreath, Matías Adrenarca y función Hipotálamo-Hipófiso-Gonadal (HHG) en pacientes nacidos pequeños para edad gestacional (PEG) en función de la caracterización molecular del gen del Receptor de Hormona de Crecimiento (GHRd3/d3, GHRd3/fl, GHRfl/fl) en población Argentina |
| topic_facet |
Hormona Crecimiento Receptor PEG Ciencias de la vida |
| description |
The Growth Hormone Receptor (GHR) mediates the action of Growth Hormone (GH) on growth and metabolism. In humans, GH is secreted by the pituitary gland and acts directly on the GHR in various cell types, generating an increase in the expression of the Insulin Like Growth Factor-1 (IGF1) as well as other genes dependent on GH.\nActually, the GHR gene is widely studied and characterized. It is located on the short arm of chromosome 5 and consists of 9 coding exons (exons 2 to 10) and 1 non-coding exon. This receptor presents an extracellular domain involved in the dimerization and binding of GH (exons 3 to 7), a transmembrane domain that binds the receptor to the cell surface (exon 8) and an intracellular domain involved in signaling by activating the via JAK-STAT (exons 9 and 10). This gene encodes for GHR, a protein that consists of 638 amino acids. Through the activation of the receptor, growth hormone is involved in a large number of physiological processes in different cell types. The biological actions of the GH can include two groups: Those of direct type (that do not require mediators) as their actions on the growth cartilage, hydrocarbon and lipid metabolism; and those of indirect type (mediated by insulin-like growth factors or IGFs) as a large part of the action on growth and protein and hydrocarbon metabolism.\nSeveral polymorphisms associated to the GHR gene have been described, being one of the most frequent the deletion of the complete exon 3 of the gene (GHRd3), which generates the loss of 22 amino acids and the A24D substitution in the N-terminal end of the extracellular domain of the receptor. The genotypic frequency of this polymorphism was analyzed in several studies and in various human populations, reporting frequencies from 2-27% in homozygosis and 15-60% in heterozygosis depending on the population under study. Although there are significant variations between the different populations, in all cases it is a frequent variant. Since its discovery to date, this polymorphism has been widely studied, as it is found in a highly conserved site in different mammalian species and consists in the deletion of a complete exon without affecting the function of the protein or its affinity for the growth hormone. These characteristics suggest that it could play an important role in adaptive mechanisms, in growth and in the response to pharmacological treatment with growth hormone.\nThere is large evidence to support the theory that this polymorphism is involved in several clinical aspects related to growth, hydrocarbon metabolism and puberal development.\nOBJECTIVES:\n- Development of a previously described technique to detect both alleles of the GHR gene (GHRfl and GHRd3).\n- Study the allelic frequency of the GHRd3 polymorphism in our population.\n- Analyze the genotypic variants of the GHR gene (GHRd3/d3, GHRd3/fl, GHRfl/fl) and its relationship with growth in SGA children, as well as with the early onset of adrenarche, the activation of the HPG axis in these patients and the hydrocarbon metabolism.\n- Study the presence of exon 3 of the GHR gene in messenger RNA from different patients and correlate the results with the genotypes of these patients.\nMATERIALS AND METHODS:\nIn the present study, we analyzed 65 SGA patients and 94 patients with appropriate weight and height for gestational age (AGE). In all cases, data were obtained at birth and at the age of evaluation. The AGE patients were used to obtain the genotypic frequencies in the population.\nAll samples were analyzed by duplex PCR, using a previously described technique for the identification of GHR gene transcripts with retention (GHRfl) or exclusion (GHRd3) of exon 3. The genotypes of all patients were evaluated together with auxological data obtained at birth, at the study age and at pubertal age in those cases in which it was possible. It was considered SGA to all children with a history of intrauterine growth retardation confirmed during pregnancy control or born with a weight below -2SDS for their gestational age and gender. When gestational age was not available, SGA was considered to be a newborn with a birth weight less than 2.5kg.\nThe presence of exon 3 of the GHR gene in messenger RNA was analyzed in placental samples by an RT-PCR technique, followed by PCR, both previously described.\nRESULTS:\nThe frequency in our population was 48% for the homozygous GHRfl genotype, 38% for the heterozygous genotype and 14% for the homozygous GHRd3 genotype. They reached Hardy-Weinberg equilibrium.\nNo differences were found in the anthropometric data at birth between the homozygous groups for the GHRfl allele (GHRfl/GHRfl) and carriers of the GHRd3 allele (GHRd3/-). The proportion of SGA patients carrying the d3 allele who experienced spontaneous compensatory growth (catch-up) was greater than in the homozygous GHRfl group. The difference in height between the moment of assessment and the body length at birth (? height) was greater for the carriers of the GHRd3 variant. Other auxological parameters were not significantly different between the carriers of both genotypes.\nIGF1 and IGFBP3 values in pre-puberal patients prior to the initiation of treatment with rhGH did not show significant differences between genotypes.\nThe age of puberal onset in both sexes was similar between the carriers of the variant GHRd3 and the GHRfl. There were also no differences in the prevalence of early puberty in both groups. SDHEA values in prepuberty did not show significant differences between subgroups of GHR variants.\nThe values of glycemia, insulin and HOMA index in SGA patients without treatment with rhGH in prepuberty did not show significant differences based on the allelic variant of GHR. No differences were found in other clinical parameters such as weight and body mass index.\nIn respect to GHR expression, at the end of the study, all the placentas genotyped presented the GHRd3/GHRfl or GHRfl/GHRfl genotypes. There was not any homozygous GHRd3 placenta. In all cases, the transcripts observed perfectly match the genotype obtained, indicating that all the isoforms present in the patient's genome would be expressed in the evaluated tissue.\nCONCLUSIONS:\nThe genotypic frequency of the GHRd3 polymorphism in the study population is similar to the results obtained by different groups in other populations worldwide. Regarding growth, although no differences were observed in prenatal growth or in serum levels of IGF1, a significant variation in spontaneous postnatal growth was observed between both groups studied.\nIn our study, no significant differences were found in the age of puberal onset in women or in males according to the GHR polymorphism. There are very few research that studied this topic previously, so the evidence is poor and no large comparisons can be made, but our data can be useful as a starting point in the subject.\nRegarding the hydrocarbon metabolism, there were no differences based on the GHRd3 polymorphism. The results previously published by various authors show great controversy regarding this issue and we believe our study provides extra data to try to elucidate this topic.\nWith regards to the assays of GHR expression in healthy placentas, the results show that for each genotype, all the expected isoforms were found. This indicates in that tissue no splicing mechanism would occur to originate an isoform not present in the patient's genome. This is the first time that this study has been performed in placentas and this could explain the differences observed in the results published years ago. It is convenient to continue studying this phenomenon in order to obtain patients with a homozygous genotype for the GHRd3 allele.\nIt would be important to increase the size of the population under study in order to obtain a more representative population. This will allow a more complete analysis of the effect that the polymorphism could have on the different variables studied. |
| author2 |
Marino, Roxana |
| author_facet |
Marino, Roxana Pujana Pentreath, Matías |
| format |
Tesis de maestría Tesis de maestría acceptedVersion |
| author |
Pujana Pentreath, Matías |
| author_sort |
Pujana Pentreath, Matías |
| title |
Adrenarca y función Hipotálamo-Hipófiso-Gonadal (HHG) en pacientes nacidos pequeños para edad gestacional (PEG) en función de la caracterización molecular del gen del Receptor de Hormona de Crecimiento (GHRd3/d3, GHRd3/fl, GHRfl/fl) en población Argentina |
| title_short |
Adrenarca y función Hipotálamo-Hipófiso-Gonadal (HHG) en pacientes nacidos pequeños para edad gestacional (PEG) en función de la caracterización molecular del gen del Receptor de Hormona de Crecimiento (GHRd3/d3, GHRd3/fl, GHRfl/fl) en población Argentina |
| title_full |
Adrenarca y función Hipotálamo-Hipófiso-Gonadal (HHG) en pacientes nacidos pequeños para edad gestacional (PEG) en función de la caracterización molecular del gen del Receptor de Hormona de Crecimiento (GHRd3/d3, GHRd3/fl, GHRfl/fl) en población Argentina |
| title_fullStr |
Adrenarca y función Hipotálamo-Hipófiso-Gonadal (HHG) en pacientes nacidos pequeños para edad gestacional (PEG) en función de la caracterización molecular del gen del Receptor de Hormona de Crecimiento (GHRd3/d3, GHRd3/fl, GHRfl/fl) en población Argentina |
| title_full_unstemmed |
Adrenarca y función Hipotálamo-Hipófiso-Gonadal (HHG) en pacientes nacidos pequeños para edad gestacional (PEG) en función de la caracterización molecular del gen del Receptor de Hormona de Crecimiento (GHRd3/d3, GHRd3/fl, GHRfl/fl) en población Argentina |
| title_sort |
adrenarca y función hipotálamo-hipófiso-gonadal (hhg) en pacientes nacidos pequeños para edad gestacional (peg) en función de la caracterización molecular del gen del receptor de hormona de crecimiento (ghrd3/d3, ghrd3/fl, ghrfl/fl) en población argentina |
| publisher |
Facultad de Farmacia y Bioquímica |
| publishDate |
2019 |
| url |
http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_3168 http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_3168.dir/3168.PDF |
| work_keys_str_mv |
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| _version_ |
1766017530994884608 |
| spelling |
I28-R145-HWA_31682022-03-03 The Growth Hormone Receptor (GHR) mediates the action of Growth Hormone (GH) on growth and metabolism. In humans, GH is secreted by the pituitary gland and acts directly on the GHR in various cell types, generating an increase in the expression of the Insulin Like Growth Factor-1 (IGF1) as well as other genes dependent on GH.\nActually, the GHR gene is widely studied and characterized. It is located on the short arm of chromosome 5 and consists of 9 coding exons (exons 2 to 10) and 1 non-coding exon. This receptor presents an extracellular domain involved in the dimerization and binding of GH (exons 3 to 7), a transmembrane domain that binds the receptor to the cell surface (exon 8) and an intracellular domain involved in signaling by activating the via JAK-STAT (exons 9 and 10). This gene encodes for GHR, a protein that consists of 638 amino acids. Through the activation of the receptor, growth hormone is involved in a large number of physiological processes in different cell types. The biological actions of the GH can include two groups: Those of direct type (that do not require mediators) as their actions on the growth cartilage, hydrocarbon and lipid metabolism; and those of indirect type (mediated by insulin-like growth factors or IGFs) as a large part of the action on growth and protein and hydrocarbon metabolism.\nSeveral polymorphisms associated to the GHR gene have been described, being one of the most frequent the deletion of the complete exon 3 of the gene (GHRd3), which generates the loss of 22 amino acids and the A24D substitution in the N-terminal end of the extracellular domain of the receptor. The genotypic frequency of this polymorphism was analyzed in several studies and in various human populations, reporting frequencies from 2-27% in homozygosis and 15-60% in heterozygosis depending on the population under study. Although there are significant variations between the different populations, in all cases it is a frequent variant. Since its discovery to date, this polymorphism has been widely studied, as it is found in a highly conserved site in different mammalian species and consists in the deletion of a complete exon without affecting the function of the protein or its affinity for the growth hormone. These characteristics suggest that it could play an important role in adaptive mechanisms, in growth and in the response to pharmacological treatment with growth hormone.\nThere is large evidence to support the theory that this polymorphism is involved in several clinical aspects related to growth, hydrocarbon metabolism and puberal development.\nOBJECTIVES:\n- Development of a previously described technique to detect both alleles of the GHR gene (GHRfl and GHRd3).\n- Study the allelic frequency of the GHRd3 polymorphism in our population.\n- Analyze the genotypic variants of the GHR gene (GHRd3/d3, GHRd3/fl, GHRfl/fl) and its relationship with growth in SGA children, as well as with the early onset of adrenarche, the activation of the HPG axis in these patients and the hydrocarbon metabolism.\n- Study the presence of exon 3 of the GHR gene in messenger RNA from different patients and correlate the results with the genotypes of these patients.\nMATERIALS AND METHODS:\nIn the present study, we analyzed 65 SGA patients and 94 patients with appropriate weight and height for gestational age (AGE). In all cases, data were obtained at birth and at the age of evaluation. The AGE patients were used to obtain the genotypic frequencies in the population.\nAll samples were analyzed by duplex PCR, using a previously described technique for the identification of GHR gene transcripts with retention (GHRfl) or exclusion (GHRd3) of exon 3. The genotypes of all patients were evaluated together with auxological data obtained at birth, at the study age and at pubertal age in those cases in which it was possible. It was considered SGA to all children with a history of intrauterine growth retardation confirmed during pregnancy control or born with a weight below -2SDS for their gestational age and gender. When gestational age was not available, SGA was considered to be a newborn with a birth weight less than 2.5kg.\nThe presence of exon 3 of the GHR gene in messenger RNA was analyzed in placental samples by an RT-PCR technique, followed by PCR, both previously described.\nRESULTS:\nThe frequency in our population was 48% for the homozygous GHRfl genotype, 38% for the heterozygous genotype and 14% for the homozygous GHRd3 genotype. They reached Hardy-Weinberg equilibrium.\nNo differences were found in the anthropometric data at birth between the homozygous groups for the GHRfl allele (GHRfl/GHRfl) and carriers of the GHRd3 allele (GHRd3/-). The proportion of SGA patients carrying the d3 allele who experienced spontaneous compensatory growth (catch-up) was greater than in the homozygous GHRfl group. The difference in height between the moment of assessment and the body length at birth (? height) was greater for the carriers of the GHRd3 variant. Other auxological parameters were not significantly different between the carriers of both genotypes.\nIGF1 and IGFBP3 values in pre-puberal patients prior to the initiation of treatment with rhGH did not show significant differences between genotypes.\nThe age of puberal onset in both sexes was similar between the carriers of the variant GHRd3 and the GHRfl. There were also no differences in the prevalence of early puberty in both groups. SDHEA values in prepuberty did not show significant differences between subgroups of GHR variants.\nThe values of glycemia, insulin and HOMA index in SGA patients without treatment with rhGH in prepuberty did not show significant differences based on the allelic variant of GHR. No differences were found in other clinical parameters such as weight and body mass index.\nIn respect to GHR expression, at the end of the study, all the placentas genotyped presented the GHRd3/GHRfl or GHRfl/GHRfl genotypes. There was not any homozygous GHRd3 placenta. In all cases, the transcripts observed perfectly match the genotype obtained, indicating that all the isoforms present in the patient's genome would be expressed in the evaluated tissue.\nCONCLUSIONS:\nThe genotypic frequency of the GHRd3 polymorphism in the study population is similar to the results obtained by different groups in other populations worldwide. Regarding growth, although no differences were observed in prenatal growth or in serum levels of IGF1, a significant variation in spontaneous postnatal growth was observed between both groups studied.\nIn our study, no significant differences were found in the age of puberal onset in women or in males according to the GHR polymorphism. There are very few research that studied this topic previously, so the evidence is poor and no large comparisons can be made, but our data can be useful as a starting point in the subject.\nRegarding the hydrocarbon metabolism, there were no differences based on the GHRd3 polymorphism. The results previously published by various authors show great controversy regarding this issue and we believe our study provides extra data to try to elucidate this topic.\nWith regards to the assays of GHR expression in healthy placentas, the results show that for each genotype, all the expected isoforms were found. This indicates in that tissue no splicing mechanism would occur to originate an isoform not present in the patient's genome. This is the first time that this study has been performed in placentas and this could explain the differences observed in the results published years ago. It is convenient to continue studying this phenomenon in order to obtain patients with a homozygous genotype for the GHRd3 allele.\nIt would be important to increase the size of the population under study in order to obtain a more representative population. This will allow a more complete analysis of the effect that the polymorphism could have on the different variables studied. Fil: Pujana Pentreath, Matías. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Buenos Aires, Argentina Marino, Roxana Facultad de Farmacia y Bioquímica Belgorosky, Alicia Pujana Pentreath, Matías 2019-10-23 El Receptor de la Hormona de Crecimiento (GHR) media la acción de la Hormona de Crecimiento (GH) sobre el crecimiento y metabolismo. En humanos, la GH es secretada por la glándula pituitaria y actúa directamente sobre el GHR en diversos tipos celulares, generando un aumento en la expresión del Factor de Crecimiento Insulino-Simil-1 (IGF1) así como de otros genes dependientes de GH.\nEn la actualidad el gen GHR se encuentra ampliamente estudiado y caracterizado. Se localiza en el brazo corto del cromosoma 5 y consiste en 9 exones codificantes (exones 2 al 10) y 1 exón no codificante. Dicho receptor presenta un dominio extracelular involucrado en la dimerización y unión de la GH (exones 3 al 7), un dominio transmembrana que ancla el receptor a la superficie celular (exón 8) y un dominio intracelular involucrado en la señalización mediante la activación de la vía JAK-STAT (exones 9 y 10). Dicho gen codifica para el GHR, una proteína que consta de 638 aminoácidos. A través de la activación del receptor, la hormona de crecimiento está involucrada en un gran número de procesos fisiológicos en distintos tipos celulares. Las acciones biológicas de la GH pueden englobar dos grupos: Aquellas de tipo directo (que no requieren mediadores) como sus acciones sobre el cartílago de crecimiento, metabolismo hidrocarbonado y lipídico; y aquellas de tipo indirecto (mediadas por factores de crecimiento símil insulina o IGFs) como gran parte de la acción sobre el crecimiento y el metabolismo proteico e hidrocarbonado.\nSe han descripto varios polimorfismos asociados al gen GHR, siendo uno de los más frecuentes la deleción del exón 3 completo del gen (GHRd3), el cual genera la pérdida de 22 aminoácidos y la sustitución A24D en el extremo N-terminal del dominio extracelular del receptor. La frecuencia genotípica de este polimorfismo fue analizada en diversos estudios y en diversas poblaciones humanas. Encontrándose frecuencias de 2 a 27% en homocigosis y de 15-60% en heterocigosis dependiendo de la población en estudio. Si bien existen variaciones significativas entre las distintas poblaciones, en todos los casos se trata de una variante frecuente. Desde su descubrimiento al día de hoy este polimorfismo ha sido ampliamente estudiado, ya que se encuentra en un sitio altamente conservado en distintas especies de mamíferos y consiste en la deleción de un exón completo sin afectar la función de la proteína ni su afinidad por la hormona decrecimiento. Estas características sugieren que podría jugar un rol importante en mecanismos adaptativos, en el crecimiento y en la respuesta al tratamiento farmacológico con hormona de crecimiento.\nExiste amplia evidencia que apoya la teoría de que este polimorfismo está implicado en varios aspectos clínicos relacionados con el crecimiento, el metabolismo hidrocarbonado y el desarrollo puberal.\nOBJETIVOS:\n- Puesta a punto de una técnica anteriormente descripta para detectar ambos alelos del gen GHR (GHRfl y GHRd3).\n- Estudiar la frecuencia alélica del polimorfismo GHRd3 en nuestra población.\n- Analizar las variantes genotípicas del gen GHR (GHRd3/d3, GHRd3/fl, GHRfl/fl) y su relación con el crecimiento en niños nacidos PEG, así como con el inicio precoz de la adrenarca, la activación del eje HHG en dichos pacientes y el metabolismo hidrocarbonado.\n- Estudiar la presencia del exón 3 del gen GHR en ARN mensajero de diferentes pacientes y correlacionar los resultados con los genotipos de dichos pacientes.\nMATERIALES Y METODOS:\nEn el presente estudio se analizaron 65 pacientes PEG y 94 pacientes con peso y talla adecuados para edad gestacional (AEG). En todos los casos se obtuvieron datos al nacimiento y a la edad de evaluación. Los pacientes AEG fueron utilizados para obtener las frecuencias genotípicas en la población.\nTodas las muestras fueron analizadas mediante PCR duplex, utilizando una técnica previamente descripta para la identificación de los transcriptos del gen GHR con la retención (GHRfl) ó la exclusión (GHRd3) del exón 3. Se evaluó en conjunto el genotipo de todos los pacientes junto con datos auxológicos obtenidos al nacimiento, a la edad de estudio y en edad puberal en los casos en los que fue posible. Se consideró PEG a todos los niños con antecedentes de retardo de crecimiento intrauterino constatado durante el control del embarazo o nacido con un peso por debajo de -2SDS para su edad gestacional y género. Cuando la edad gestacional no estaba disponible, se consideró PEG a aquel recién nacido con un peso de nacimiento menor a 2.5kg.\nLa presencia del exón 3 del gen GHR en ARN mensajero fue analizada en muestras de placenta mediante una técnica de RT-PCR, seguida de PCR, ambas previamente descriptas.\n RESULTADOS:\nLa frecuencia en nuestra población fue de 48% para el genotipo homocigota GHRfl, 38% para el genotipo heterocigota y 14% para el genotipo homocigota GHRd3. Las mismas cumplen con la Ley de Hardy-Weinberg.\nNo se encontraron diferencias en los datos antropométricos al nacimiento entre los grupos homocigota para el alelo GHRfl (GHRfl/GHRfl) y portadores del alelo GHRd3 (GHRd3/-). La proporción de pacientes PEG portadores del alelo d3 que experimentaron crecimiento compensador espontaneo (catch-up) fue mayor que los homocigota GHRfl. La diferencia de estatura entre el momento de valoración y la longitud corporal al nacimiento (? talla) fue mayor para los portadores de la variante GHRd3. Otros parámetros auxológicos no fueron diferentes entre los portadores de los diferentes genotipos.\nLos valores de IGF1 e IGFBP3 en pacientes pre-puberales previos al inicio del tratamiento con rhGH no presentaron diferencias significativas entre genotipos.\nLa edad de inicio puberal en ambos sexos fue similar entre los portadores de la variante GHRd3 y los GHRfl. Tampoco se observaron diferencias en la prevalencia de pubertad temprana en ambos grupos. Los valores de SDHEA en prepubertad no mostraron diferencias significativas entre los subgrupos de variantes de GHR.\nLos valores de glucemia, insulina e índice HOMA en pacientes PEG sin tratamiento con rhGH en prepubertad no mostraron diferencias significativas en función de la variante alélica del GHR. Tampoco se encontraron diferencias en otros parámetros clínicos como peso e índice de masa corporal.\nCon respecto a la expresión del GHR, a la fecha de finalización del estudio no se genotipificó ninguna placenta homocigota para el alelo GHRd3. En todos los casos los transcriptos evidenciados condicen perfectamente con el genotipo obtenido, indicando que en el tejido evaluado se expresarían todas las isoformas presentes en el genoma del paciente.\nCONCLUSIONES:\nLa frecuencia genotípica del polimorfismo GHRd3 en la población en estudio se asemeja a los resultados obtenidos por diferentes grupos en otras poblaciones a nivel mundial. Con respecto al crecimiento, si bien no se observaron diferencias en el crecimiento prenatal ni en los niveles séricos de IGF1, si se observó una variación significativa en el crecimiento posnatal espontaneo entre ambos grupos estudiados.\nEn nuestro estudio, no se encontraron diferencias significativas en cuanto a la edad de inicio puberal en mujeres ni en varones en función del polimorfismo de GHR. Son muy pocos los estudios que trataron este tema previamente, por lo que la evidencia es escasa y no se pueden hacer grandes comparaciones, pero nuestros datos son de utilidad como punto de partida en el tema.\nLos resultados en cuanto al metabolismo hidrocarbonado indican que no hubo diferencias en base al polimorfismo GHRd3. Pero los resultados publicados previamente por diversos autores muestran una gran controversia con respecto a este tema y nuestro estudio aporta un resultado más para tratar de elucidar este asunto.\nCon respecto a los ensayos de expresión del GHR en placentas sanas, los resultados muestran que para cada genotipo, se encontraron todas las isoformas esperadas, lo que indica que en ese tejido no ocurriría ningún mecanismo de splicing que dé origen a una isoforma no presente en el genoma del paciente. Es la primera vez que se realiza este estudio en placenta y esto podría explicar las diferencias que se observan en los resultados publicados hace años por los distintos investigadores. Es conveniente continuar estudiando este fenómeno con el objetivo de obtener pacientes con genotipo homocigota para el alelo GHRd3.\nSería importante aumentar el tamaño de la población en estudio de manera de obtener una población más representativa. Esto permitirá hacer un análisis más completo del efecto que podría tener el polimorfismo sobre las diferentes variables estudiadas. application/pdf Rivolta, Carina De Brasi, Carlos Rey, Rodolfo Hormona Crecimiento Receptor PEG spa Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by-nc-nd/2.5/ar/ Ciencias de la vida Adrenarca y función Hipotálamo-Hipófiso-Gonadal (HHG) en pacientes nacidos pequeños para edad gestacional (PEG) en función de la caracterización molecular del gen del Receptor de Hormona de Crecimiento (GHRd3/d3, GHRd3/fl, GHRfl/fl) en población Argentina info:eu-repo/semantics/masterThesis info:ar-repo/semantics/tesis de maestría info:eu-repo/semantics/acceptedVersion http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=afamaster&cl=CL1&d=HWA_3168 http://repositoriouba.sisbi.uba.ar/gsdl/collect/afamaster/index/assoc/HWA_3168.dir/3168.PDF |