{"id":2233,"date":"2023-03-30T20:10:05","date_gmt":"2023-03-30T23:10:05","guid":{"rendered":"https:\/\/ibyme.org.ar\/investigacion\/?page_id=2233"},"modified":"2025-02-07T17:26:15","modified_gmt":"2025-02-07T20:26:15","slug":"lineas-de-investigacion","status":"publish","type":"page","link":"https:\/\/ibyme.org.ar\/investigacion\/laboratorios\/fisiopatologia-hormonal\/lineas-de-investigacion\/","title":{"rendered":"L\u00edneas de Investigaci\u00f3n"},"content":{"rendered":"<p><div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-1 fusion-flex-container has-pattern-background has-mask-background fusion-parallax-none hundred-percent-fullwidth non-hundred-percent-height-scrolling\" 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class=\"fusion-title-heading title-heading-left\" style=\"margin:0;\">Fisiopatolog\u00eda Hormonal<\/h1><\/div><\/div><\/div><\/div><\/div><div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-4 fusion-flex-container has-pattern-background has-mask-background nonhundred-percent-fullwidth non-hundred-percent-height-scrolling\" style=\"--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-flex-wrap:wrap;\" ><div class=\"fusion-builder-row fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap\" style=\"max-width:1248px;margin-left: calc(-4% \/ 2 );margin-right: calc(-4% \/ 2 );\"><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-2 fusion_builder_column_1_1 1_1 fusion-flex-column\" style=\"--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:1.92%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:1.92%;--awb-width-medium:100%;--awb-order-medium:0;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-order-small:0;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;\"><div class=\"fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column\"><div class=\"fusion-title title fusion-title-2 fusion-sep-none fusion-title-text fusion-title-size-two\" style=\"--awb-text-color:var(--awb-color5);--awb-font-size:22px;\"><h2 class=\"fusion-title-heading title-heading-left\" style=\"font-family:&quot;Red Hat Display&quot;;font-style:normal;font-weight:700;margin:0;font-size:1em;\">L\u00edneas de Investigaci\u00f3n<\/h2><\/div><\/div><\/div><\/div><\/div><div class=\"fusion-fullwidth fullwidth-box fusion-builder-row-5 fusion-flex-container has-pattern-background has-mask-background nonhundred-percent-fullwidth non-hundred-percent-height-scrolling\" style=\"--awb-border-radius-top-left:0px;--awb-border-radius-top-right:0px;--awb-border-radius-bottom-right:0px;--awb-border-radius-bottom-left:0px;--awb-flex-wrap:wrap;\" ><div class=\"fusion-builder-row fusion-row fusion-flex-align-items-flex-start fusion-flex-content-wrap\" style=\"max-width:1248px;margin-left: calc(-4% \/ 2 );margin-right: calc(-4% \/ 2 );\"><div class=\"fusion-layout-column fusion_builder_column fusion-builder-column-3 fusion_builder_column_1_1 1_1 fusion-flex-column\" style=\"--awb-bg-size:cover;--awb-width-large:100%;--awb-margin-top-large:0px;--awb-spacing-right-large:1.92%;--awb-margin-bottom-large:20px;--awb-spacing-left-large:1.92%;--awb-width-medium:100%;--awb-order-medium:0;--awb-spacing-right-medium:1.92%;--awb-spacing-left-medium:1.92%;--awb-width-small:100%;--awb-order-small:0;--awb-spacing-right-small:1.92%;--awb-spacing-left-small:1.92%;\"><div class=\"fusion-column-wrapper fusion-column-has-shadow fusion-flex-justify-content-flex-start fusion-content-layout-column\"><div class=\"fusion-text fusion-text-1\"><p>En el laboratorio, en b\u00fasqueda de tratamientos alternativos para prolactinomas resistentes a agonistas dopamin\u00e9rgicos, nos enfocamos en distintos sistemas inhibitorios de la funci\u00f3n lactotropa:<\/p>\n<div id=\"attachment_6099\" style=\"width: 810px\" class=\"wp-caption aligncenter\"><img decoding=\"async\" aria-describedby=\"caption-attachment-6099\" class=\"wp-image-6099 size-fusion-800\" src=\"https:\/\/ibyme.org.ar\/investigacion\/wp-content\/uploads\/2023\/04\/lineas-de-inv-acoplado-800x649.jpg\" alt=\"\" width=\"800\" height=\"649\" srcset=\"https:\/\/ibyme.org.ar\/investigacion\/wp-content\/uploads\/2023\/04\/lineas-de-inv-acoplado-200x162.jpg 200w, https:\/\/ibyme.org.ar\/investigacion\/wp-content\/uploads\/2023\/04\/lineas-de-inv-acoplado-300x243.jpg 300w, https:\/\/ibyme.org.ar\/investigacion\/wp-content\/uploads\/2023\/04\/lineas-de-inv-acoplado-400x325.jpg 400w, https:\/\/ibyme.org.ar\/investigacion\/wp-content\/uploads\/2023\/04\/lineas-de-inv-acoplado-600x487.jpg 600w, https:\/\/ibyme.org.ar\/investigacion\/wp-content\/uploads\/2023\/04\/lineas-de-inv-acoplado-768x623.jpg 768w, https:\/\/ibyme.org.ar\/investigacion\/wp-content\/uploads\/2023\/04\/lineas-de-inv-acoplado-800x649.jpg 800w, https:\/\/ibyme.org.ar\/investigacion\/wp-content\/uploads\/2023\/04\/lineas-de-inv-acoplado-1024x831.jpg 1024w, https:\/\/ibyme.org.ar\/investigacion\/wp-content\/uploads\/2023\/04\/lineas-de-inv-acoplado-1200x974.jpg 1200w, https:\/\/ibyme.org.ar\/investigacion\/wp-content\/uploads\/2023\/04\/lineas-de-inv-acoplado-1536x1247.jpg 1536w, https:\/\/ibyme.org.ar\/investigacion\/wp-content\/uploads\/2023\/04\/lineas-de-inv-acoplado.jpg 1778w\" sizes=\"(max-width: 800px) 100vw, 800px\" \/><\/p>\n<p id=\"caption-attachment-6099\" class=\"wp-caption-text\">Esquema representativo de los sistemas inhibitorios que act\u00faan sobre la proliferaci\u00f3n y liberaci\u00f3n de prolactina en lactotropos.<\/p>\n<\/div>\n<ul>\n<li><strong><u>TGF\u03b21<\/u><\/strong><\/li>\n<\/ul>\n<p>Esta prote\u00edna es una fuerte citoquina que colabora con la funci\u00f3n inhibitoria de dopamina sobre los lactotropos. Controla la proliferaci\u00f3n celular y la secreci\u00f3n de prolactina.<\/p>\n<p>Nuestra investigaci\u00f3n demostr\u00f3 que en prolactinomas de diferentes modelos animales de prolactinomas TGF\u03b21, sus receptores y activadores se encuentran disminuidos y, adem\u00e1s, un tratamiento farmacol\u00f3gico con an\u00e1logos sint\u00e9ticos de trombospondina I (TSP-I), un fuerte activador de la citoquina fue exitoso para activar y aumentar la biodisponibilidad de TGF\u03b21, reducir el tama\u00f1o tumoral y disminuir la prolactina en suero. Esto nos indica que los an\u00e1logos de TSP-I pueden ser una alternativa viable para el tratamiento de prolactinomas resistentes a agonistas dopamin\u00e9rgicos.<\/p>\n<p>&nbsp;<\/p>\n<ul>\n<li><strong><u>KLK1<\/u><\/strong><\/li>\n<\/ul>\n<p>Otro activador de TGF\u03b21 descripto es calicre\u00edna tisular (KLK1), una proteasa conocida por clivar al quinin\u00f3geno produciendo quininas, p\u00e9ptidos bioactivos del sistema calicre\u00edna-quininas (KKS) que act\u00faan sobre los receptores B1R y B2R. Recientemente se encontr\u00f3 que el B2R se encuentra sobreexpresado (unas 20 veces) en prolactinomas humanos respecto a hip\u00f3fisis normales. Se ha descripto que B2R y el receptor de dopamina tipo 2 (D2R) pueden formar un heterod\u00edmero funcional y que la activaci\u00f3n de B2R en el heterod\u00edmero anula la cascada de se\u00f1alizaci\u00f3n de D2R. En el laboratorio demostramos que los diversos componentes del KKS se expresan localmente en la hip\u00f3fisis (quininasas I y II, receptores de bradiquinina, B1R y B2R) y su expresi\u00f3n se altera con el desarrollo de un prolactinoma. Dopamina regula positivamente la expresi\u00f3n de KLK1 y BRs mientras que estradiol inhibe la expresi\u00f3n g\u00e9nica de KLK1 y B2R, en concordancia con la acci\u00f3n de KLK1 de inducir la liberaci\u00f3n de prolactina. Adem\u00e1s, validamos la interacci\u00f3n de B2R y D2R en prolactinomas humanos y en adenomas no funcionantes humanos.<\/p>\n<p>&nbsp;<\/p>\n<ul>\n<li><strong><u>Activinas<\/u><\/strong><\/li>\n<\/ul>\n<p>Las Activinas son prote\u00ednas que forman parte de la familia de prote\u00ednas TGF\u03b2 y se conforman de homo y heterod\u00edmeros de subunidades \u03b2a y\/o \u03b2b. Fueron estudiadas en principio por su efecto estimulatorio de FSH (la hormona fol\u00edculo estimulante), pero luego se determin\u00f3 su funci\u00f3n inhibitoria sobre los lactotropos. En el laboratorio demostramos que las subunidades que conforman las activinas, sus receptores y su actividad biol\u00f3gica sobre los lactotropos espec\u00edficamente se encontraban disminuidas en nuestros modelos animales de prolactinomas, indicando su potencial como blanco terap\u00e9utico.<\/p>\n<ul>\n<li>A su vez, las Activinas son antagonizadas por las inhibinas de origen gonadal, por lo que al estudiar el efecto de una ovariectom\u00eda en nuestros modelos murinos de prolactinomas observamos una inversi\u00f3n del fenotipo tumoral debido a la recuperaci\u00f3n de este sistema inhibitorio.<\/li>\n<\/ul>\n<p>&nbsp;<\/p>\n<ul>\n<li><strong><u>Receptores de Progesterona<\/u><\/strong><\/li>\n<\/ul>\n<p>Si bien los receptores de progesterona nucleares son los m\u00e1s estudiados, tambi\u00e9n se han descripto en los \u00faltimos a\u00f1os los receptores de progesterona de membrana. En nuestro laboratorio demostramos que el 15% de los receptores de progesterona expresados en hip\u00f3fisis son de membrana, y el tipo celular que mayormente los expresa es el lactotropo. M\u00e1s interesante a\u00fan, demostramos que la estimulaci\u00f3n de estos receptores activa v\u00edas de se\u00f1alizaci\u00f3n inhibitorias de la secreci\u00f3n de prolactina, entre las cuales se encuentra la activaci\u00f3n de TGF\u03b21. Progesterona act\u00faa tambi\u00e9n a nivel del hipot\u00e1lamo y demostramos que el 80% de los receptores de progesterona hipotal\u00e1micos son de membrana, y su activaci\u00f3n lleva al incremento en la liberaci\u00f3n de dopamina, regulador inhibitorio clave del lactotropo.<\/p>\n<p>&nbsp;<\/p>\n<p><strong><u>Diferencias sexuales:<\/u><\/strong> En cada sistema inhibitorio estudiado hacemos foco en las diferencias que encontramos entre sexos. Esto es de mucha importancia debido a que en la cl\u00ednica la incidencia de prolactinomas entre sexos es de 10:1 en el sexo biol\u00f3gico femenino:masculino en edad f\u00e9rtil, y luego se equipara 1:1 en mayores de 50 a\u00f1os. La regulaci\u00f3n del lactotropo por estradiol es un punto clave a tener en cuenta para entender estas diferencias.<\/p>\n<p>&nbsp;<\/p>\n<\/div><\/div><\/div><\/div><\/div><\/p>\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":16,"featured_media":0,"parent":2230,"menu_order":2,"comment_status":"closed","ping_status":"closed","template":"100-width.php","meta":{"_acf_changed":false,"inline_featured_image":false,"wpupg_custom_link":[],"wpupg_custom_link_behaviour":["default"],"wpupg_custom_link_nofollow":[],"wpupg_custom_image":[],"wpupg_custom_image_id":[],"footnotes":""},"page_category":[],"class_list":["post-2233","page","type-page","status-publish","hentry"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.6 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>L\u00edneas de Investigaci\u00f3n - IBYME<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/ibyme.org.ar\/investigacion\/laboratorios\/fisiopatologia-hormonal\/lineas-de-investigacion\/\" \/>\n<meta property=\"og:locale\" content=\"es_ES\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"L\u00edneas de Investigaci\u00f3n - 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