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.
Key words
adrenal cortex - glucocorticoids - HPA-axis - aldosterone
