Homer 1 gene products are involved in the regulation of synaptic transmission and plasticity. Beside other deficits, the
Homer 1 knockout (KO) mice show distinct behavioural abnormalities, such as anxiety and depression-like behaviours. In addition, we recently reported that the global deletion of the
Homer 1 proteins in mice leads to a conspicuous endocrine phenotype linked to
hypertrophy of the adrenal cortex, elevated basal and/or
adrenocorticotropic hormone-induced
corticosterone and
aldosterone release in vitro and in vivo, as well as a drastic increase in the
adrenocorticotropic hormone receptor mRNA in the adrenocortical cells. Interestingly, the basal secretion of
adrenocorticotropic hormone was not changed in these mutants, which is in line with our recent observations, suggesting that the central limb of the hypothalamic-pituitary-adrenal axis (namely hypothalamic
corticotropin-releasing hormone levels and the activation of its neurons in response to restraint stress) is not affected in the
Homer 1 KO mice. On the contrary, the elevation of both plasma and intra-adrenal
corticosterone and
aldosterone concentrations in these mutants clearly indicates that the alteration primarily occurred in the adrenal cortex. We propose that excessive
steroid release may contribute to depression- and anxiety-like behaviours and that the
Homer 1 gene products may be involved in the pathogenesis of these stress-related
mood disorders.