'Central' Actions of Corticosteroid Signaling Suggested by Constitutive Knockout of Corticosteroid Receptors in Small Fish

Abstract

This review highlights recent studies of the functional implications of corticosteroids in some important behaviors of model fish, which are also relevant to human nutrition homeostasis. The primary actions of corticosteroids are mediated by glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), which are transcription factors. Zebrafish and medaka models of GR- and MR-knockout are the first constitutive corticosteroid receptor-knockout animals that are viable in adulthood. Similar receptor knockouts in mice are lethal. In this review, we describe the physiological and behavioral changes following disruption of the corticosteroid receptors in these models. The GR null model has peripheral changes in nutrition metabolism that do not occur in a mutant harboring a point mutation in the GR DNA-binding domain. This suggests that these are not "intrinsic" activities of GR. On the other hand, we propose that integration of visual responses and brain behavior by corticosteroid receptors is a possible "intrinsic"/principal function potentially conserved in vertebrates.

Keywords: behavior; brain; glucocorticoid; metabolism; mineralocorticoid; vision.

Figure 1

Photomicrograph of mineralocorticoid receptor (MR) in-situ hybridization in medaka brain. MR expression is restricted to a number of important areas that likely correspond to homologous brain regions containing MR in other vertebrates including those of humans [35]. Telencephalic regions exhibiting higher MR expression include the ventral parts of the lateral zone of the dorsal telencephalon (putative fish homologue of the mammalian hippocampus [36]), and commissural and subcommissural nuclei of the telencephalon (V; putative fish homologue to the mammalian amygdala) [36]. In the diencephalon, the hypothalamic preoptic area, inferior lobe of the hypothalamus, and glomerulus complex of the thalamus exhibit MR expression, as do the mesencephalic tegmentum and granular layer of the optic tectum. MR expressed markedly in some regions of the cerebellum. CCe, corpus cerebelli; D, dorsal telencephalic area; TeO, tectum opticum; TL, torus longitudinalis; V, ventral telencephalic area. The detailed expression profiles are described in Sakamoto et al. [13]. Ubiquitously expressed GR in the brains of rodent and fish, as well as MR expression in the rodent brain, have been illustrated elsewhere [15,37,38]. Scale bar: 100 μm.