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PMID:16141355

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Citation

Mantamadiotis, T, Kretz, O, Ridder, S, Bleckmann, SC, Bock, D, Gröne, HJ, Malaterre, J, Dworkin, S, Ramsay, RG and Schütz, G (2006) Hypothalamic 3',5'-cyclic adenosine monophosphate response element-binding protein loss causes anterior pituitary hypoplasia and dwarfism in mice. Mol. Endocrinol. 20:204-11

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.

Links

PubMed Online version:10.1210/me.2005-0195

Keywords

Animals; Brain/metabolism; Crosses, Genetic; Cyclic AMP Response Element-Binding Protein/genetics; Cyclic AMP Response Element-Binding Protein/metabolism; Dwarfism/genetics; Dwarfism/metabolism; Female; Fertility/genetics; Growth Hormone/metabolism; Growth Hormone-Releasing Hormone/metabolism; Hypothalamus/metabolism; Insulin-Like Growth Factor I/metabolism; Lactation/genetics; Male; Mice; Mice, Mutant Strains; Pituitary Gland, Anterior/abnormalities; Pituitary Gland, Anterior/metabolism; Somatostatin/metabolism

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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References

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