Linked Life Data

12514220

Source:http://linkedlifedata.com/resource/pubmed/id/12514220

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-1-6
pubmed:abstractText
The initiation of mammalian puberty requires the activation of hypothalamic neurons secreting the neuropeptide luteinizing hormone-releasing hormone (LHRH). It is thought that this activation is caused by changes in trans-synaptic input to LHRH neurons. More recently, it has been postulated that the pubertal increase in LHRH secretion in female animals also requires neuron-glia signaling mediated by growth factors of the epidermal growth factor (EGF) family and their astrocytic erbB receptors. Although it appears clear that functional astrocytic erbB1 receptors are necessary for the timely advent of puberty, the physiological contribution that erbB4 receptors may make to this process has not been established. To address this issue, we generated transgenic mice expressing a dominant-negative erbB4 receptor (DN-erbB4) under the control of the GFAP promoter, which targets transgene expression to astrocytes. DN-erbB4 expression is most abundant in hypothalamic astrocytes, where it blocks the ligand-dependent activation of glial erbB4 and erbB2 receptors, without affecting erbB1 (EGF) receptor signaling. Mice carrying the transgene exhibit delayed sexual maturation and a diminished reproductive capacity in early adulthood. These abnormalities are related to a deficiency in pituitary gonadotropin hormone secretion, caused by impaired release of LHRH, the hypothalamic neuropeptide that controls sexual development. In turn, the reduction in LHRH release is caused by the inability of hypothalamic astrocytes to respond to neuregulin (NRG) with production of prostaglandin E(2), which in wild-type animals mediates the stimulatory effect of astroglial erbB receptor activation on neuronal LHRH release. Thus, neuron-astroglia communication via NRG-erbB4/2 receptor signaling appears to be essential for the timely unfolding of the developmental program by which the brain controls mammalian sexual maturation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
230-9
pubmed:dateRevised
2011-11-2
pubmed:meshHeading
pubmed-meshheading:12514220-Animals, pubmed-meshheading:12514220-Astrocytes, pubmed-meshheading:12514220-Cells, Cultured, pubmed-meshheading:12514220-Dinoprostone, pubmed-meshheading:12514220-Female, pubmed-meshheading:12514220-Fertility, pubmed-meshheading:12514220-Follicle Stimulating Hormone, pubmed-meshheading:12514220-Glial Fibrillary Acidic Protein, pubmed-meshheading:12514220-Gonadotropin-Releasing Hormone, pubmed-meshheading:12514220-Hypothalamus, pubmed-meshheading:12514220-Kinetics, pubmed-meshheading:12514220-Mice, pubmed-meshheading:12514220-Mice, Transgenic, pubmed-meshheading:12514220-Mutation, pubmed-meshheading:12514220-Neuregulins, pubmed-meshheading:12514220-Promoter Regions, Genetic, pubmed-meshheading:12514220-Receptor, Epidermal Growth Factor, pubmed-meshheading:12514220-Receptor, erbB-2, pubmed-meshheading:12514220-Sex Characteristics, pubmed-meshheading:12514220-Sexual Maturation, pubmed-meshheading:12514220-Signal Transduction
pubmed:year
2003
pubmed:articleTitle
Normal female sexual development requires neuregulin-erbB receptor signaling in hypothalamic astrocytes.
pubmed:affiliation
Division of Neuroscience, Oregon Regional Primate Research Center/Oregon Health Sciences University, Beaverton, Oregon 97006, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't