titoli, abstracts, parole chiave >>>
Enhanced at puberty 1 (EAP1) is a new transcriptional regulator of the female neuroendocrine reproductive axis

Heger, Sabine and Mastronardi, Claudio and Dissen, Gregory A. and Lomniczi, Alejandro and Cabrera, Ricardo and Roth, Christian L. and Jung, Heike and Galimi, Francesco and Sippell, Wolfgang and Ojeda, Sergio R. (2007) Enhanced at puberty 1 (EAP1) is a new transcriptional regulator of the female neuroendocrine reproductive axis. The Journal of Clinical Investigation, Vol. 117 (8), p. 2145-2154. eISSN 1558-8238. Article.

[img]
Preview
Full text disponibile come PDF Richiede visualizzatore di PDF come GSview, Xpdf o Adobe Acrobat Reader
1246Kb

DOI: 10.1172/JCI31752

Abstract

The initiation of mammalian puberty and the maintenance of female reproductive cycles are events controlled by hypothalamic neurons that secrete the decapeptide gonadotropin-releasing hormone (GnRH). GnRH secretion is, in turn, controlled by changes in neuronal and glial inputs to GnRH-producing neurons. The hierarchical control of the process is unknown, but it requires coordinated regulation of these cell-cell interactions. Here we report the functional characterization of a gene (termed enhanced at puberty 1 [EAP1]) that appears to act as an upstream transcriptional regulator of neuronal networks controlling female reproductive function. EAP1 expression increased selectively at puberty in both the nonhuman primate and rodent hypothalamus. EAP1 encoded a nuclear protein expressed in neurons involved in the inhibitory and facilitatory control of reproduction. EAP1 transactivated genes required for reproductive function, such as GNRH1, and repressed inhibitory genes, such as preproenkephalin. It contained a RING finger domain of the C3HC4 subclass required for this dual transcriptional activity. Inhibition of EAP1 expression, targeted to the rodent hypothalamus via lentivirus-mediated delivery of EAP1 siRNAs, delayed puberty, disrupted estrous cyclicity, and resulted in ovarian abnormalities. These results suggest that EAP1 is a transcriptional regulator that, acting within the neuroendocrine brain, contributes to controlling female reproductive function.

Item Type:Article
ID Code:753
Status:Published
Refereed:Yes
Uncontrolled Keywords:Enhanced at puberty 1 (EAP1), gonadotropin-releasing hormone (GnRH), membrane-associated ring finger (C3HC4)
Subjects:Area 05 - Scienze biologiche > BIO/17 Istologia
Divisions:001 Università di Sassari > 01 Dipartimenti > Scienze biomediche
Publisher:The American Society for Clinical Investigation
eISSN:1558-8238
Publisher Policy:Depositato in conformità con la politica di copyright dell'Editore
Deposited On:18 Aug 2009 10:03

I documenti depositati in UnissResearch sono protetti dalle leggi che regolano il diritto d'autore

Repository Staff Only: item control page