title: Hypothalamic 3',5'-cyclic adenosine monophosphate response element-binding protein loss causes anterior pituitary hypoplasia and dwarfism in mice.
abstract: The principal regulation of body growth is via a cascade of hormone signals emanating from the hypothalamus, by release of GHRH, which then directs the somatotroph cells of the pituitary to release GH into the blood stream. This in turn leads to activation of signal transducer and activator of transcription 5-dependent expression of genes such as IGF-I in hepatocytes, acid labile substance, and serine protease inhibitor 2.1, resulting in body growth. Here, using conditional cAMP response element binding protein (CREB) mutant mice, we show that loss of the CREB transcription factor in the brain, but not the pituitary, results in reduced postnatal growth consistent with dwarfism caused by GH deficiency. We demonstrate that although there appears to be no significant impact upon the expression of GHRH mRNA in CREB mutant mice, the amount of GHRH peptide is reduced. These findings show that CREB is required for the efficient production of GHRH in hypothalamus, in addition to its previously reported role in pituitary GH production and somatotroph expansion.
authors.affiliation: Molecular Biology of the Cell, Deutsches Krebsforschungszentrum, Heidelberg, Germany. theo.mantamadiotis@petermac.org
authors.forename: Theo
authors.initials: T
authors.lastname: Mantamadiotis
authors.forename: Oliver
authors.initials: O
authors.lastname: Kretz
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ridder
authors.forename: Susanne C
authors.initials: SC
authors.lastname: Bleckmann
authors.forename: Dagmar
authors.initials: D
authors.lastname: Bock
authors.forename: Hermann-Josef
authors.initials: HJ
authors.lastname: Gröne
authors.forename: Jordane
authors.initials: J
authors.lastname: Malaterre
authors.forename: Sebastian
authors.initials: S
authors.lastname: Dworkin
authors.forename: Robert G
authors.initials: RG
authors.lastname: Ramsay
authors.forename: Günther
authors.initials: G
authors.lastname: Schütz
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D003433:Crosses, Genetic; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D004392:Dwarfism / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005298:Fertility / Q000235:genetics; D013006:Growth Hormone / Q000378:metabolism; D013007:Growth Hormone-Releasing Hormone / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007774:Lactation / Q000235:genetics; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D010903:Pituitary Gland, Anterior / Q000002:abnormalities* / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone