The SREB (Super-Conserved Receptors Expressed in Brain) family of receptors, comprised of SREB1, 2, 3a, and 3b, is highly conserved across vertebrates. These receptors are suggested to play roles in immunity, energy metabolism, and regulation of the reproductive hormonal cascade. While recent studies have focused on characterizing the individual and collective functions of SREBs, including their ligands and downstream signaling pathways, most research has been conducted using mammalian models, leaving their roles in non-mammalian vertebrates, such as fish, largely unexplored.
Here we present the experimental design and findings of an in vitro study using three comparative fish models, including Zebrafish (Danio rerio), Mummichog (Fundulus heteroclitus), and Green Spotted Pufferfish (Dichotomyctere nigroviridis), each representing distinct SREB expression patterns. Two newly developed synthetic agonists, PT-91 and 8535, have been demonstrated to activate SREB receptors, providing novel tools to investigate their function. Ovarian tissue from each species was exposed to these compounds, followed by transcriptomic analysis and steroid quantification to assess gene regulation and steroidogenic responses.
Pathway analysis of Zebrafish PT-91 treatments upregulated genes linked to energy production and cell movement, while 8535 increased expression of genes associated with reproductive function. Preliminary analysis in Green-Spotted Pufferfish demonstrated a weaker response, with PT-91 upregulating transcriptional processes and 8535 upregulating protein synthesis pathways, both at low levels. Ongoing work includes expanded analyses in green-spotted pufferfish and mummichogs, as well as steroid quantification across all species.
The results of this study provide new insights into the functional roles of SREB receptors in fish reproduction and may inform the development and improved spawning induction strategies for aquaculture. Future in vivo studies will build upon these findings by investigating the ability of these agonist to induce spawning in fish.