‘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.

Polystyrene nanoplastics disrupt glucose metabolism and cortisol levels with a possible link to behavioural changes in larval zebrafish

“…Glucocorticoid effects on the brain are highly complex and brain region-, dose- as well as time-dependent 35–37 . Recently such interferences with the neural system have been observed for fish like trout, medaka, and zebrafish 47–49 , and could potentially lead to aberrant stress-coping mechanisms (e.g. stress recovery patterns and anxiety-related behaviours).…”

Progesterone: An enigmatic ligand for the mineralocorticoid receptor

“…Studies of corticosteroid activation of the MR in zebrafish [79][80][81][82][83] and medaka [70,71,84,85] are beginning to elucidate the role of the MR in extra-renal tissues. We suggest parallel studies in zebrafish and medaka to investigate progesterone activation of the MR in heart, brain, lung, kidney, gill, liver, ovary, testis and other organs that contain an MR. For example, analysis of gene transcription using RNA-Seq of these organs in zebrafish exposed to progesterone, cortisol, 11-deoxycorticosterone and aldosterone should provide important insights into similarities and differences in gene expression due to these steroids.…”

“…to provide tissues in which the MR is not activated by progesterone, but can still be activated by circulating cortisol and deoxycorticosterone. This approach provides an opportunity to elucidate the role of progesterone in zebrafish, and it may uncover novel physiological functions for the MR in ray-finned fish, which are only beginning to be understood [71,[79][80][81][82][83][84][85] . Unexpectedly, although the MR is expressed in kidney and gill, the MR does not appear to regulate sodium uptake, the classical "mineralocorticoid function", in fish.…”

Introducing the Amphibious Mudskipper Goby as a Unique Model to Evaluate Neuro/Endocrine Regulation of Behaviors Mediated by Buccal Sensation and Corticosteroids

“…In addition to being key components of the stress axis, GR is expressed ubiquitously and MR is expressed in several important areas (Table 1) in the fish central nervous system, with likely correspondence to regions of expression in other vertebrates [4,66,77,[79][80][81][82][83]. MR is highly expressed in telencephalic regions, which include the ventral parts of the lateral zone of the dorsal telencephalon (putative fish homologue of the mammalian hippocampus [84]), and commissural and subcommissural nuclei of the telencephalon (putative fish homologue of the mammalian amygdala [84]).…”

“…These findings suggest that GRs/MRs are critical for many physiological and behavioral responses, such as the regulation of salt intake, mood, appetite, exploratory behavior and visual responses [77,[85][86][87]. Indeed, zebrafish and medaka models with constitutive GR or MR knockout fail to integrate these brain behavior and visual responses as well as regulate the stress axis, although they can grow and osmoregulate [77,80,[88][89][90][91][92][93][94][95][96][97]. The simple aquatic preference of mudskippers may also reflect these behaviors.…”