The First Fifteen Years of Steroid Receptor Research in Zebrafish; Characterization and Functional Analysis of the Receptors

Animal science

Immune modulations by glucocorticoids: from molecular biology to clinical research

Animal science

Modeling inflammation in zebrafish for the development of anti-inflammatory drugs

Animal science

Glucocorticoid-induced exacerbation of mycobacterial infection is associated with a reduced phagocytic capacity of macrophages

Animal science

Detailed analysis of zebrafish larval behaviour in the light dark challenge assay shows that diel hatching time determines individual variation

Research on stress coping style, i.e., the response of an organism to adverse conditions, which is constant over time and context, gained momentum in recent years, to better understand behavioural patterns in animal welfare. However, knowledge about the ontogeny of stress coping style is still limited. Here, we performed a detailed analysis of the light dark challenge behavioural assay in zebrafish larvae, where after acclimation in ambient light sudden alternating dark and light phases elicit an anxiety-like response. A principal component analysis on parameters related to locomotion (distance moved, swimming velocity, acceleration, mobility) and directionality (angular velocity, meandering of swimming path) revealed independence between the parameters determined in the light and the dark phases of the assay, indicating unrelated generalised behaviours per phase. However, high collinearity was observed between behavioural parameters within the same phase, indicating a robust response to the stimulus within behavioural phenotypes. Subsequently, this assay was used to determine the correlation between individual hatching time and the behavioural phenotype. The results show that fish that had hatched during daytime have a stronger behavioural response to the dark phase at 5 days post-fertilisation in locomotion related parameters and a weaker response in directionality related parameters, than fish that had hatched during nighttime. These results show that behavioural responses to the light dark challenge assay are robust and can be generalised for the light and the dark phase, and that diel hatching time may determine the behavioural phenotype of an individual.Animal science

The role of the glucocorticoid receptor in the regulation of diel rhythmicity

Microbial Biotechnolog

Candidates for membrane progestin receptors: past approaches and future challenges

Progestins have a broad range of functions in reproductive biology. Many rapid nongenomic actions of progestins have been identified, including induction of oocyte maturation, modulation of reproductive signaling in the brain, rapid activation of breast cancer cell signaling, induction of the acrosomal reaction and hypermotility in mammalian sperm. Currently, there are three receptor candidates for mediating rapid progestin actions: (1) membrane progestin receptors (mPRs); (2) progestin receptor membrane components (PGRMCs); and (3) nuclear progestin receptors (nPRs). The recently-described mPR family of proteins has seven integral transmembrane domains and mediates signaling via G-protein coupled pathways. The PGRMCs have a single transmembrane with putative Src homology domains for potential activation of second messengers. The classical nPRs, in addition to having well defined transcriptional activity, can also mediate rapid activation of intracellular signaling pathways. However, details of the mechanisms by which these three classes of progestin receptors mediate rapid intracellular signaling and their subcellular localization remain unclear. In addition, mPRs, nPRs and PGRMCs exhibit overlapping expression and functions in multiple tissues, implying potential interactions during oocyte maturation, parturition, and breast cancer signaling in individual cells. However, the overwhelming majority of studies to date have focused on the functions of one of these groups of receptors in isolation. This review will summarize recent findings on the three major progestin receptor candidates, emphasizing the different approaches used, some experimental pitfalls, and current controversies. We will also review evidence for the involvement of mPRs and nPRs in one of the most well-characterized nongenomic steroid actions in basal vertebrates, oocyte maturation, and conclude by suggesting some future areas of research. Clarification of the controversies surrounding the identities and localization of membrane progestin receptors may help direct future research that could advance our understanding of rapid actions of steroids.Animal science

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

Plastic nanoparticles originating from weathering plastic waste are emerging contaminants in aquatic environments, with unknown modes of action in aquatic organisms. Recent studies suggest that internalised nanoplastics may disrupt processes related to energy metabolism. Such disruption can be crucial for organisms during development and may ultimately lead to changes in behaviour. Here, we investigated the link between polystyrene nanoplastic (PSNP)-induced signalling events and behavioural changes. Larval zebrafish exhibited PSNP accumulation in the pancreas, which coincided with a decreased glucose level. By using hyperglycemic and glucocorticoid receptor (Gr) mutant larvae, we demonstrate that the PSNP-induced disruption in glucose homoeostasis coincided with increased cortisol secretion and hyperactivity in challenge phases. Our work sheds new light on a potential mechanism underlying nanoplastics toxicity in fish, suggesting that the adverse effect of PSNPs are at least in part mediated by Gr activation in response to disrupted glucose homeostasis, ultimately leading to aberrant locomotor activity

Behavioral and physiological indicators of stress coping styles in larval zebrafish

Animal science

Androgen receptor complexes probe DNA for recognition sequences by short random interactions

Owing to the tremendous progress in microscopic imaging of fluorescently labeled proteins in living cells, the insight into the highly dynamic behavior of transcription factors has rapidly increased over the past decade. However, a consistent quantitative scheme of their action is still lacking. Using the androgen receptor (AR) as a model system, we combined three different fluorescence microscopy assays: single-molecule microscopy, photobleaching and correlation spectroscopy, to provide a quantitative model of the action of this transcription factor. This approach enabled us to distinguish two types of AR-DNA binding: very brief interactions, in the order of a few hundred milliseconds, and hormone-induced longer-lasting interactions, with a characteristic binding time of several seconds. In addition, freely mobile ARs were slowed down in the presence of hormone, suggesting the formation of large AR-co-regulator complexes in the nucleoplasm upon hormone activation. Our data suggest a model in which mobile hormone-induced complexes of transcription factors and co-regulators probe DNA by briefly binding at random sites, only forming relatively stable transcription initiation complexes when bound to specific recognition sequences