Determining the Role of Progesterone Nuclear Receptor in Modulating Aggression in Male Zebrafish (Danio rerio)

Abstract

In many social animal species, aggression is an essential element in forming stable dominance hierarchies. It serves as an organizing agent for resource allocation according to social rank. However, persistently high aggressive activity among a social group could be destabilizing and have long-lasting physiological effects and be detrimental to social cohesion. Though the importance of maintaining the balance of aggression has been explored, the biochemical underpinnings that maintain social homeostasis remain poorly understood. In this thesis project, I utilize male zebrafish as a model organism to investigate the role of progestin nuclear receptor (Pgr) in regulating social aggression. As a joint effort with colleagues, we show that Pgr plays an important role in regulating aggression. We demonstrate that Pgr knockout (PgrKO) zebrafish display high levels of aggressive activity that persist over an extended time compared to wild-type animals. To determine the neurophysiological bases that underlie hyper aggressiveness of PgrKO fish, we conducted a morphological analysis of brain dopaminergic nuclei and blood hormonal measurements of testosterone and 11-ketotestosterone. We found that the PgrKO transgenic line showed an increase in the number of dopaminergic neurons in the A15 nucleus as well as an increase in the steroidogenesis of 11-ketotestosterone (11-KT) compared to WT zebrafish. Our results suggest that Pgr may work through the dopaminergic system to alter 11-KT levels to modify social aggression.