kiss1-protein--human and Hamartoma

Hypothalamic hamartomas are the most common identifiable cause of central precocious puberty (CPP). Hamartoma characteristics proposed to be associated with CPP include specific anatomic features and expression of molecules such as gonadotropin-releasing hormone (GnRH), transforming growth factor alpha (TGFalpha), and GRM1A, which encodes the type 1 metabotropic glutamate receptor alpha isoform. We sought to determine whether hamartomas that cause CPP could be distinguished by anatomic features, expression of these molecules, or expression of KISS1, whose products signal through the receptor GPR54 to stimulate GnRH release.. Clinical records and radiologic images were reviewed for 18 patients who underwent hamartoma resection for intractable seizures; 7 had precocious puberty. Resected tissue was examined for expression of GnRH, GnRH receptor (GnRHR), TGFalpha, KISS1, GPR54, and GRM1A.. Hypothalamic hamartomas associated with CPP were more likely to contact the infundibulum or tuber cinereum and were larger than hamartomas not associated with CPP. GnRH, TGFalpha, and GnRHR were expressed by all hamartomas studied. Expression of KISS1, GPR54, and GRM1A did not differ significantly between hamartomas associated and not associated with CPP.. Anatomic features rather than expression patterns of candidate molecules distinguish hypothalamic hamartomas that are associated with CPP from those that are not.

Topics: Adolescent; Child; Child, Preschool; Female; Gene Expression; Gonadotropin-Releasing Hormone; Hamartoma; Humans; Hypothalamic Diseases; Infant; Kisspeptins; Male; Puberty, Precocious; Radiography; Receptors, LHRH; Seizures; Transforming Growth Factor alpha; Tumor Suppressor Proteins

Hypothalamic hamartomas (HHs) are congenital lesions composed of neurons and astroglia. Frequently, HHs cause central precocious puberty (CPP) and/or gelastic seizures. Because HHs might express genes similar to those required for the initiation of normal puberty, we used cDNA arrays to compare the gene expression profile of an HH associated with CPP with three HHs not accompanied by sexual precocity.. Global changes in gene expression were detected using Affymetrix arrays. The results were confirmed by semiquantitative PCR, which also served to examine the expression of selected genes in the hypothalamus of female monkeys undergoing puberty.. All HHs were associated with seizures. Ten genes whose expression was increased in the HH with CPP were identified. They encode proteins involved in three key cellular processes: transcriptional regulation, cell-cell signaling, and cell adhesiveness. They include IA-1 and MEF2A, two transcription factors required for neuronal development; mGluR1 and VILIP-1, which encode proteins involved in neuronal communication, and TSG-6 that encodes a protein involved in cell adhesiveness. Of these, expression of mGluR1 also increases in the female monkey hypothalamus at puberty.. Increased expression of these genes in HHs may be relevant to the ability of some HHs to induce sexual precocity.

Topics: Adolescent; Adult; Animals; Cell Adhesion Molecules; Child; Child, Preschool; DNA-Binding Proteins; Female; Gene Expression Profiling; Gonadotropin-Releasing Hormone; Hamartoma; Humans; Hypothalamic Diseases; Kisspeptins; Macaca mulatta; Male; Oligonucleotide Array Sequence Analysis; Puberty, Precocious; Receptors, G-Protein-Coupled; Receptors, Kisspeptin-1; Receptors, Metabotropic Glutamate; Repressor Proteins; Sexual Maturation; Transforming Growth Factor alpha; Tumor Suppressor Proteins