title: Hypertrophy and altered activity of the adrenal cortex in Homer 1 knockout mice.
abstract: Homer 1 gene products are involved in synaptic transmission and plasticity, and hence, distinct behavioral abnormalities, including anxiety- and depression-like behaviors, have been observed in Homer 1 knockout (KO) mice. Here we report that Homer 1 KO mice additionally exhibit a pronounced endocrine phenotype, displaying a profoundly increased adrenal gland weight and increased adrenal/body weight ratio. Histological examinations of Homer 1 deficient adrenal glands revealed an increased size of the adrenal cortex, especially the sizes of the zona fasciculata and zona glomerulosa. Moreover, the plasma corticosterone and aldosterone were higher in Homer 1 KO than wild-type (WT) mice while the plasma ACTH levels were not different between the genotypes. The in vivo ACTH test revealed that corticosterone and aldosterone plasma levels were higher in saline injected Homer 1 KO mice than in WT mice (saline injected mice served as controls for the respective groups of ACTH-injected animals), but the magnitude of steroid responses to ACTH was similar in both genotypes. In contrast, an in vitro experiment performed on isolated cells of adrenal cortex clearly showed increased production of both steroids in response to ACTH in Homer 1 KO cells, which is in line with an ~8-fold increase in the expression of ACTH receptor mRNA in the adrenal cortex of these mutants. These results, together with the detection of Homer 1 mRNA and protein in the adrenal cortex of WT mice, indicate that Homer 1 directly affects the steroidogenic function of the adrenal glands.
authors.affiliation: Department of Molecular Neurobiology, Max-Planck-Institute for Medical Research, Jahnstraße 29, 69120 Heidelberg, Germany. Valery.Grinevich@mpimfheidelberg.mpg.de
authors.forename: V
authors.initials: V
authors.lastname: Grinevich
authors.forename: D
authors.initials: D
authors.lastname: Jezova
authors.forename: S
authors.initials: S
authors.lastname: Gambaryan
authors.forename: A
authors.initials: A
authors.lastname: Illarionova
authors.forename: A
authors.initials: A
authors.lastname: Kolleker
authors.forename: P H
authors.initials: PH
authors.lastname: Seeburg
authors.forename: M K
authors.initials: MK
authors.lastname: Schwarz
mesh_terms: D000311:Adrenal Glands / Q000187:drug effects / Q000473:pathology*; D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000450:Aldosterone / Q000097:blood; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D000072233:Homer Scaffolding Proteins; D006984:Hypertrophy / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype
chemical_list: D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone