RESUMEN
Luteinizing hormone-releasing hormone (LHRH) was first isolated in the mammalian hypothalamus and shown to be the primary regulator of the reproductive system through its initiation of pituitary gonadotropin release. Since its discovery, this form of LHRH (LHRH-I) has been shown to be one of many structural variants with a variety of roles in both the brain and peripheral tissues. Enormous interest has been focused on LHRH-I and LHRH-II and their cognate receptors as targets for designing therapies to treat cancers of the reproductive system. LHRH-I is processed by a zinc metalloendopeptidase EC 3.4.24.15 (EP24.15) that cleaves the hormone at the fifth and sixth bond of the decapeptide (Tyr(5)-Gly(6)) to form LHRH-(1-5). We have previously reported that the autoregulation of LHRH gene expression can also be mediated by its processed peptide, LHRH-(1-5). Furthermore, LHRH-(1-5) has also been shown to be involved in cell proliferation. This review will focus on the possible roles of LHRH and its processed peptide, LHRH-(1-5), in non-hypothalamic tissues.
Asunto(s)
Hormona Liberadora de Gonadotropina/análogos & derivados , Ácido Pirrolidona Carboxílico/análogos & derivados , Animales , Hormona Liberadora de Gonadotropina/química , Hormona Liberadora de Gonadotropina/metabolismo , Humanos , Especificidad de Órganos , Procesamiento Proteico-Postraduccional , Ácido Pirrolidona Carboxílico/química , Ácido Pirrolidona Carboxílico/metabolismo , Receptores LHRH/metabolismoRESUMEN
OBJECTIVE: The purpose of this study is to determine the possible role of the processed peptide of LHRH, LHRH-(1-5), in regulating growth of endometrial cancer cells. STUDY DESIGN: An endometrial cancer cell line, the Ishikawa cell line, was cultured under standard conditions and treated in a dose-dependent manner with 1 of 2 hormones, LHRH and LHRH-(1-5) to determine the ability of these peptides to regulate cellular growth. A tetrazolium-based assay was used to determine the effect these peptides have on cell proliferation. Furthermore, enzyme-linked immunosorbent assay (ELISA)-based assays were used to determine the expression of caspase-3/7 and pERK-1/2. Statistical analyses were conducted using an analysis of variance followed by Fisher LSD as the post-hoc test. RESULTS: The results show that LHRH is anti-proliferative whereas LHRH-(1-5) is proliferative on the cells. Furthermore, LHRH-(1-5) decreased caspase-3/7 and pERK1/2 expression. CONCLUSION: This is the first time LHRH-(1-5) is shown to have proliferative effects on cells.