The study of the neurons secreting the gonadotropin releasing hormone (GnRH), the hypothalamic hormone stimulating the release of pituitary gonadotropins, has been potentiated by the development of immortalized cells that specifically synthetize and secrete GnRH. Two cell lines have been obtained by targeted tumorigenesis in transgenic mice: 1) the GT1 cells (with GT1-1, GT1-3 and GT1-7 subclones), and 2) the GN cells (with the GN10, GN11 and NLT subclones). GT1 cells have been obtained from a hypothalamic tumor and exhibit the properties of fully mature GnRH secreting neurons after they reached their final destination in the hypothalamus starting from the olfactory placode. Because of their characteristics GT1 cells have been mainly utilized to investigate the secretory properties of GnRH neurons and to identify the inputs modulating their activity. By this way a consistent number of receptors responding to specific ligands (neurotransmitters, hormones, growth factors) controlling GnRH synthesis and secretion has been identified. GN cells have been derived from a tumor of the olfactory bulb and are considered to replicate the properties of immature GnRH secreting neurons still retaining the capacity of moving. Consequently these cells are used to identify and characterize the factors influencing the migratory process of GnRH neurons from the olfactory placode to the hypothalamus. It has been found that factors stimulating GnRH neuron motility include anosmin, the protein encoded by the KAL1 gene, whose mutations lead to the form of hypogonadotropic hypogonadism known as Kallmann’s syndrome, growth factors such as fibroblast growth factor, hepatocyte growth factor, vascular endothelial growth factor, and cytoskeleton associated proteins (stathmin). On the contrary GABA agonists and glucocorticoids depress GN cells motility. As a whole the findings reported in this review seem particularly important to provide further information on the central mechanisms controlling development and function of the reproductive system.

Biology of hypothalamic neurons producing gonadotropin-releasing hormone (GnRH): new information on the use of immortalized cells secreting GnRH / R. Maggi, D. Dondi, F. Piva. - In: BRASÍLIA MÉDICA. - ISSN 0524-2053. - 43:1-4(2006), pp. 40-47.

Biology of hypothalamic neurons producing gonadotropin-releasing hormone (GnRH): new information on the use of immortalized cells secreting GnRH

R. Maggi
Primo
;
D. Dondi
Secondo
;
F. Piva
Ultimo
2006

Abstract

The study of the neurons secreting the gonadotropin releasing hormone (GnRH), the hypothalamic hormone stimulating the release of pituitary gonadotropins, has been potentiated by the development of immortalized cells that specifically synthetize and secrete GnRH. Two cell lines have been obtained by targeted tumorigenesis in transgenic mice: 1) the GT1 cells (with GT1-1, GT1-3 and GT1-7 subclones), and 2) the GN cells (with the GN10, GN11 and NLT subclones). GT1 cells have been obtained from a hypothalamic tumor and exhibit the properties of fully mature GnRH secreting neurons after they reached their final destination in the hypothalamus starting from the olfactory placode. Because of their characteristics GT1 cells have been mainly utilized to investigate the secretory properties of GnRH neurons and to identify the inputs modulating their activity. By this way a consistent number of receptors responding to specific ligands (neurotransmitters, hormones, growth factors) controlling GnRH synthesis and secretion has been identified. GN cells have been derived from a tumor of the olfactory bulb and are considered to replicate the properties of immature GnRH secreting neurons still retaining the capacity of moving. Consequently these cells are used to identify and characterize the factors influencing the migratory process of GnRH neurons from the olfactory placode to the hypothalamus. It has been found that factors stimulating GnRH neuron motility include anosmin, the protein encoded by the KAL1 gene, whose mutations lead to the form of hypogonadotropic hypogonadism known as Kallmann’s syndrome, growth factors such as fibroblast growth factor, hepatocyte growth factor, vascular endothelial growth factor, and cytoskeleton associated proteins (stathmin). On the contrary GABA agonists and glucocorticoids depress GN cells motility. As a whole the findings reported in this review seem particularly important to provide further information on the central mechanisms controlling development and function of the reproductive system.
O estudo dos neurÙnios que produzem o hormÙnio liberador das gonadotrofinas (GnRH), hormÙnio hipotal‚mico que estimula a secreÁ„o das gonadotrofinas hipofis·rias, tem recebido vigoroso impulso com a disponibilidade das cÈlulas imortalizadas, que especificamente sintetizam e secretam o hormÙnio em quest„o. Duas s„o as linhas celulares obtidas por tumorigÍnese induzida em camundongos transgÍnicos: 1) as cÈlulas GT1 (com os seus subclones GT1-1, GT1-3, GT1-7) e 2) as cÈlulas GN (com os seus subclones GN10, GN11, NLT). As cÈlulas GT1 foram derivadas de um tumor hipotal‚mico. Pode-se constatar que elas s„o dotadas de propriedades dos neurÙnios maduros secretores de GnRH, que completaram o seu trajeto da sua sede de origem, o placÛide olfatÛrio, atÈ a sua sede definitiva, o hipot·lamo, e j· perderam a capacidade de mover-se. Por essas caracterÌsticas, as cÈlulas GT1 s„o utilizadas sobretudo para o estudo das propriedades secretÛrias dos neurÙnios que produzem o GnRH e para identificar os sinais que ali chegam. Pode-se assim evidenciar uma sÈrie de receptores, que, ativados pelos seus ligantes (neurotransmissores, hormÙnios, fatores de crescimento), modulam a sÌntese e a secreÁ„o do GnRH. As cÈlulas GN foram retiradas de um tumor do bulbo olfatÛrio, portanto, elas s„o consideradas mais semelhantes aos neurÙnios imaturos secretores de GnRH que ainda est„o desenvolvendo o processo de migraÁ„o do placÛide olfatÛrio atÈ o hipot·lamo. Desse modo, tais cÈlulas s„o utilizadas sobretudo para identificar e caracterizar os fatores que possam influenciar os processos de migraÁ„o dos neurÙnios que produzem o GnRH. Em particular, pode-se constatar que a motilidade dos neurÙnios secretores desse hormÙnio È estimulada pela anosmina, a proteÌna codificada pelo gene KAL1, que, nas suas formas mutantes, ocasiona o hipogonadismo hipogonadotrÛfico conhecido como a sÌndrome de Kallmann, por alguns fatores de crescimento (fator de crescimento de fibroblasto, fator de crescimento de hepatÛcito, fator de crescimento de endotÈlio vascular) ou proteÌnas associadas ao citoesqueleto (stathmina). Os agonistas do GABA e os glicocorticÛides, por sua vez, deprimem a motilidade das cÈlulas GN. No seu conjunto, os estudos apresentados nesta sucinta revis„o parecem particularmente promissores para um posterior aprofundamento da compreens„o dos mecanismos centrais que regulam o desenvolvimento e a atividade do aparelho reprodutor.
GnRH; neuroni; migrazione; ipothalamo; gonadotropin-releasing hormone; GT1; GN;Kallmann syndrome
Settore BIO/09 - Fisiologia
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