title: Ablation of Egr2-positive cells in male mouse anterior pituitary leads to atypical isolated GH deficiency.
abstract: In this study, we have investigated the expression and function of the transcription factor early growth response factor 2 (Egr2)/Krox20 in the developing anterior pituitary. Egr2 is initially expressed in all differentiating hormonal cells types, but its expression is mostly restricted to the somatotroph lineage after birth. Egr2 knockout results in anterior pituitary hypoplasia. However, the analysis of a conditional mutant demonstrates that this phenotype does not originate from a lack of Egr2 expression in the pituitary. Using an Egr2 allele driving a Cre-activable toxin gene, we performed a genetic ablation of Egr2-positive cells in the pituitary. During the postnatal period, this ablation leads to specific and progressive depletion of the somatotroph population, creating a novel model of early-onset isolated GH deficiency (GHD). Mutant animals were subjected to a complete metabolic analysis, revealing atypical and expected features. Consistent with an adult-onset isolated GHD model, mutant animals are hypoglycemic and display increased insulin sensitivity and glucose clearance. This latter phenotype is in contrast to the glucose intolerance observed in another early-onset GHD model. Surprisingly, increased insulin sensitivity is not accompanied by a modified balance between fat and lean tissues, but by reduced metabolic adaptability between glucose and lipid oxidation conditions. This suggests that the relationship between these metabolic features and insulin sensitivity should be reconsidered. In conclusion, our mutant may be a valuable genetic model with which to study the effects of long-term GH deficiency, in conditions of normal pancreatic function and unaffected balance between fat and glucose metabolism.
authors.affiliation: Ecole Normale Supérieure, 46 rue d'Ulm, 75005 Paris, France.
authors.forename: Yassine Xavier
authors.initials: YX
authors.lastname: Bouchoucha
authors.forename: Patrick
authors.initials: P
authors.lastname: Charnay
authors.forename: Pascale
authors.initials: P
authors.lastname: Gilardi-Hebenstreit
mesh_terms: D000483:Alleles; D000818:Animals; D051767:Early Growth Response Protein 2 / Q000378:metabolism*; D013006:Growth Hormone / Q000097:blood; D007018:Hypopituitarism / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D051379:Mice; D010903:Pituitary Gland, Anterior / Q000166:cytology* / Q000378:metabolism*
chemical_list: D051767:Early Growth Response Protein 2; C497327:Egr2 protein, mouse; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone