RESUMO
Corticotropin (ACTH) and melanotropin (MSH) peptides (melanocortins) are produced not only in the pituitary but also in the brain, with highest concentrations in the arcuate nucleus of the hypothalamus and the commisural nucleus of the solitary tract. We have identified a receptor for MSH and ACTH peptides that is specifically expressed in regions of the hypothalamus and limbic system. This melanocortin receptor (MC3-R) is found in neurons of the arcuate nucleus known to express proopiomelanocortin (POMC) and in a subset of the nuclei to which these neurons send projections. The MC3-R is 43% identical to the MSH receptor present in melanocytes and is strongly coupled to adenylyl cyclase. Unlike the MSH or ACTH receptors, MC3-R is potently activated by gamma-MSH peptides, POMC products that were named for their amino acid homology with alpha- and beta-MSH, but lack melanotropic activity. The primary biological role of the gamma-MSH peptides is not yet understood. The location and properties of this receptor provide a pharmacological basis for the action of POMC peptides produced in the brain and possibly a specific physiological role for gamma-MSH.
Assuntos
Encéfalo/metabolismo , Hipotálamo/metabolismo , Sistema Límbico/metabolismo , Hormônios Estimuladores de Melanócitos/metabolismo , Pró-Opiomelanocortina/metabolismo , Receptores de Melanocortina/metabolismo , Receptores do Hormônio Hipofisário/metabolismo , Adenilil Ciclases/genética , Adenilil Ciclases/metabolismo , Hormônio Adrenocorticotrópico/química , Sequência de Aminoácidos , Animais , Northern Blotting , Clonagem Molecular , Humanos , Hibridização In Situ , Cinética , Masculino , Hormônios Estimuladores de Melanócitos/química , Dados de Sequência Molecular , Especificidade de Órgãos , Reação em Cadeia da Polimerase/métodos , Prosencéfalo/metabolismo , RNA Mensageiro/análise , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor Tipo 3 de Melanocortina , Receptores de Melanocortina/análise , Receptores de Melanocortina/química , Receptores do Hormônio Hipofisário/análise , Receptores do Hormônio Hipofisário/química , Proteínas Recombinantes de Fusão/metabolismo , Homologia de Sequência de AminoácidosAssuntos
Hormônio Adrenocorticotrópico/metabolismo , Hormônios Estimuladores de Melanócitos/metabolismo , Receptores de Superfície Celular/genética , Receptores do Hormônio Hipofisário/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Clonagem Molecular , DNA , Humanos , Camundongos , Dados de Sequência Molecular , Família Multigênica , Oligodesoxirribonucleotídeos , Reação em Cadeia da Polimerase , Estrutura Secundária de Proteína , Receptores da Corticotropina , Receptores do Hormônio Hipofisário/metabolismo , Homologia de Sequência de Aminoácidos , TransfecçãoRESUMO
Coat colors in the chestnut horse, the yellow Labrador retriever, the red fox, and one type of yellow mouse are due to recessive alleles at the extension locus. Similarly, dominant alleles at this locus are often responsible for dark coat colors in mammals, such as the melanic form of the leopard, Panthera pardus. We show here that the murine extension locus encodes the melanocyte-stimulating hormone (MSH) receptor. In mice, the recessive yellow allele (e) results from a frameshift that produces a prematurely terminated, nonfunctioning receptor. The sombre (Eso and Eso-3J) and tobacco darkening (Etob) alleles, which both have dominant melanizing effects, results from point mutations that produce hyperactive MSH receptors. The Eso-3J receptor is constitutively activated, while the Etob receptor remains hormone responsive and produces a greater activation of its effector, adenylyl cyclase, than does the wild-type allele.
Assuntos
Hormônios Estimuladores de Melanócitos/fisiologia , Camundongos/genética , Mutação Puntual , Receptores do Hormônio Hipofisário/genética , Alelos , Sequência de Aminoácidos , Animais , Sequência de Bases , Mapeamento Cromossômico , Mutação da Fase de Leitura , Glicoproteínas de Membrana/genética , Dados de Sequência Molecular , Oligodesoxirribonucleotídeos/química , Fenótipo , Pigmentação , Reação em Cadeia da PolimeraseRESUMO
The gene that encodes phosphoglycerate kinase in Drosophila melanogaster (Pgk) has been isolated and characterized. There is a single copy of Pgk in the Drosophila genome located at cytogenetic position 23A1-2. Transcripts of Pgk are 1.6 kb long and are found during development with a profile similar to the expression pattern of other genes of the glycolytic pathway. There are substantial amounts of maternal transcript in early embryos which decline in abundance until mid-embryogenesis when transcript levels increase; levels remain high, during larval stages, fall during pupariation and rise again at emergence. The nucleotide sequence of the Pgk gene reveals two small introns, one of which is at a position identical to the site of an intron found in Pgk genes from other organisms. The Pgk gene has no TATA box in the region of transcription initiation and has multiple transcription initiation sites that are closely spaced within 110 nucleotides of the translation start site.
Assuntos
Drosophila melanogaster/enzimologia , Drosophila melanogaster/genética , Fosfoglicerato Quinase/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Northern Blotting , Southern Blotting , DNA/genética , DNA/isolamento & purificação , Sondas de DNA , Drosophila melanogaster/fisiologia , Embrião não Mamífero/fisiologia , Genes , Humanos , Hibridização In Situ , Íntrons , Dados de Sequência Molecular , Biossíntese de Proteínas , RNA Mensageiro/genética , RNA Mensageiro/isolamento & purificação , Mapeamento por Restrição , Homologia de Sequência de Aminoácidos , Transcrição GênicaRESUMO
High affinity TSH binding has been reported in a variety of tissues other than the thyroid, most commonly in adipocytes and lymphocytes. This extrathyroidal binding of TSH has been documented most carefully in the guinea pig epididymal fat pad, where it has been postulated to be due to the presence of the TSH receptor (TSH-R). Extrathyroidal TSH-R expression has also been theorized to account for the associated dermopathy and ophthalmopathy seen in some patients with Graves' disease. We have isolated a cDNA encoding a fragment of the guinea pig TSH-R and have used this as a probe to study the distribution of TSH-R mRNA in the guinea pig. We show here that TSH-R mRNA is expressed in most white adipose tissues and in all brown adipose tissues tested. However, no expression was detectable by Northern analysis or in most polymerase chain reaction experiments using guinea pig retroorbital tissues, bringing into question the proposed role of the TSH-R as an autoantigen in autoimmune ophthalmopathy. The presence of significant amounts of TSH-R mRNA in most adipose tissues suggests a more important role for TSH in lipolysis and thermogenesis than previously thought.
