RESUMEN
Ghrelin is a recently identified endogenous ligand of the GH secretagogue (GHS) receptor. It was originally isolated from the stomach, but has also been shown to be present in the rat hypothalamus. It is a 28-amino acid peptide with an unusual octanoylated serine 3 at the N-terminal end of the molecule, which is crucial for its biological activity. Synthetic GHSs stimulate GH release via both the hypothalamus and the pituitary, and the GHS receptor (GHS-R) has been shown by us and others to be present in the pituitary. We investigated whether ghrelin messenger ribonucleic acid (mRNA) and peptide are present in the normal human hypothalamus and in normal and adenomatous human pituitary. RNA was extracted from pituitary tissue removed at autopsy and transsphenoidal surgery (n = 62), and ghrelin and GHS-R type 1a and 1b mRNA levels were investigated using real-time RT-PCR. Both ghrelin and GHS-R mRNA were detected in all samples. Corticotroph tumors showed significantly less expression of ghrelin mRNA, whereas GHS-R mRNA levels were similar to those in normal pituitary tissue. Gonadotroph tumors showed a particularly low level of expression of GHS-R mRNA. Immunohistochemistry, using a polyclonal antibody against the C-terminal end of the ghrelin molecule, revealed positive staining in the homolog of the arcuate nucleus in the human hypothalamus and in both normal and abnormal human pituitary. Pituitary tumor ghrelin peptide content was demonstrated using two separate RIA reactions for the N-terminal and C-terminal ends of the molecule. Both forms were present in normal and abnormal pituitaries, with 5 +/- 2.5% octanoylated (active) ghrelin (mean +/- SD) present as a percentage of the total. We suggest that the presence of ghrelin mRNA and peptide in the pituitary implies that the locally synthesized hormone may have an autocrine/paracrine modulatory effect on pituitary hormone release.
Asunto(s)
Hipotálamo/metabolismo , Tumores Neuroendocrinos/genética , Hormonas Peptídicas , Péptidos/genética , Hipófisis/metabolismo , Neoplasias Hipofisarias/genética , Receptores de Superficie Celular/genética , Receptores Acoplados a Proteínas G , Transcripción Genética , Adulto , Anciano , Animales , Secuencia de Bases , Cartilla de ADN , Femenino , Mucosa Gástrica/metabolismo , Ghrelina , Hormona de Crecimiento Humana/metabolismo , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Datos de Secuencia Molecular , Tumores Neuroendocrinos/patología , Péptidos/análisis , Neoplasias Hipofisarias/patología , Reacción en Cadena de la Polimerasa , ARN Mensajero/análisis , ARN Mensajero/genética , Ratas , Receptores de Ghrelina , Valores de ReferenciaRESUMEN
BACKGROUND: Some metallic compounds, especially of zirconium, can cause cell mediated granulomatous inflammation of the skin. Pigment granules containing compounds of aluminium, silicon, and titanium have been observed within macrophages in the wall of the small intestine in health and in Crohn's disease. Zirconium compounds can be ingested in toothpaste. AIM: To determine in a pilot study if granulomatous sensitivity can be detected to compounds of these metals or silicon after injection into the skin of patients with Crohn's disease. SUBJECTS: Eight patients with Crohn's disease known to have had granulomata in the intestine and not currently treated with corticosteroids, and two healthy controls. METHOD: Two intradermal injections each of 0.1 ml of a 0.02% suspension of one of the compounds made in the abdominal wall of each subject. The site was marked and full thickness skin biopsy performed six weeks later. RESULT: A foreign body granuloma was observed on histological examination of two biopsy specimens but no evidence of a cell mediated response in any subject. CONCLUSION: No support was found for the hypothesis that Crohn's disease is due to a specific sensitivity to ingested metallic or silicon compounds.
Asunto(s)
Óxido de Aluminio/efectos adversos , Enfermedad de Crohn/complicaciones , Dermatitis por Contacto/etiología , Granuloma de Cuerpo Extraño/etiología , Dióxido de Silicio/efectos adversos , Titanio/efectos adversos , Circonio/efectos adversos , Óxido de Aluminio/administración & dosificación , Estudios de Casos y Controles , Enfermedad de Crohn/inmunología , Dermatitis por Contacto/complicaciones , Femenino , Granuloma de Cuerpo Extraño/complicaciones , Humanos , Pruebas Intradérmicas , Masculino , Proyectos Piloto , Dióxido de Silicio/administración & dosificación , Titanio/administración & dosificación , Circonio/administración & dosificaciónRESUMEN
Cloned fragments of members of the Drosophila and mouse major heat shock (hsp70) gene family were used to demonstrate that homologous sequences are present in the rabbit genome. After a physiologically relevant increase in body temperature of 3 degrees C, transcription of inducible hsp70 genes is detected in both the fetal and maternal brain and kidney. The induced hsp70 gene transcripts decay rapidly after whole body hyperthermia subsides. Transcripts of constitutively expressed member(s) of the hsp70 gene family, the heat shock cognate genes (hsc70), are detected in unstressed fetal and maternal rabbit tissues.