Статья

New insights into SREB orphan receptor roles in the ovary, using comparative transcriptomics across three fishes

Charles HeyderTropical Aquaculture Laboratory, Program in Fisheries and Aquatic Sciences, School of Forest, Fisheries, and Geomatics Sciences, Institute of Food and Agricultural Sciences, University of Florida , Ruskin, FL, 33570 ,Casey A. MurrayTropical Aquaculture Laboratory, Program in Fisheries and Aquatic Sciences, School of Forest, Fisheries, and Geomatics Sciences, Institute of Food and Agricultural Sciences, University of Florida , Ruskin, FL, 33570 ,Philip K. E. GranithPharmaceutical Science Laboratory (PSL – Pharmacy) and Structural Bioinformatics Laboratory (SBL – Biochemistry), Faculty of Science and Engineering, Åbo Akademi University , FI-20500 Turku ,Mukhriddin MakhkamovInstitute for Advanced Studies, New Uzbekistan University , Movarounnahr str. 1, Tashkent 100000 ,Emma BourgetBiology Department, University of Maine at Farmington , Farmington, ME, 04938 ,Isabella CainBiology Department, University of Maine at Farmington , Farmington, ME, 04938 ,Breckon DavidsonBiology Department, University of Maine at Farmington , Farmington, ME, 04938 ,Taylor-Jeffery DooneBiology Department, University of Maine at Farmington , Farmington, ME, 04938 ,Joanna KorasadowiczBiology Department, University of Maine at Farmington , Farmington, ME, 04938 ,Nora HullBiology Department, University of Maine at Farmington , Farmington, ME, 04938 ,Jade MartensBiology Department, University of Maine at Farmington , Farmington, ME, 04938 ,Ryan Martin-HacheyBiology Department, University of Maine at Farmington , Farmington, ME, 04938 ,Keira McGrathBiology Department, University of Maine at Farmington , Farmington, ME, 04938 ,Haley StewartBiology Department, University of Maine at Farmington , Farmington, ME, 04938 ,Jamoliddin RazzokovDepartment of Natural Sciences, Karshi State Technical University , Mustaqillik Avenue street 225, Kashkadarya 180100 ,Parthiban MarimuthuPharmaceutical Science Laboratory (PSL – Pharmacy) and Structural Bioinformatics Laboratory (SBL – Biochemistry), Faculty of Science and Engineering, Åbo Akademi University , FI-20500 Turku ,Thanigaimalai PillaiyarTübingen Center for Academic Drug Discovery and Development, Eberhard Karls University Tübingen , 72076 Tübingen ,Julien HansonLaboratory of Molecular Pharmacology, GIGA Research Institute & CIRM, University of Liège , Liège ,Christopher J. MartyniukCenter for Environmental and Human Toxicology, Department of Physiological Sciences, College of Veterinary Medicine, University of Florida , Gainesville, FL, 32611 ,Matthew A. DiMaggioTropical Aquaculture Laboratory, Program in Fisheries and Aquatic Sciences, School of Forest, Fisheries, and Geomatics Sciences, Institute of Food and Agricultural Sciences, University of Florida , Ruskin, FL, 33570 ,Timothy S. BretonBiology Department, University of Maine at Farmington , Farmington, ME, 04938 ,

2026en

ABI

Аннотация

Super-conserved Receptors Expressed in Brain (SREB) are a family of orphan G protein coupled receptors with three members in most vertebrates (GPR27 or SREB1, GPR85 or SREB2, and GPR173 or SREB3). They are associated with diverse physiological processes, ranging from glucose homeostasis to ovarian development. Despite a lack of confirmed ligands, our understanding of these receptors has increased based on interactions with putative SREB3 ligands such as phoenixin (PNX) and the development of synthetic SREB1 agonists (A8535 and PT-91). However, to date no studies have used these agonists in any complex vertebrate system. The objective of this study was to compare the in vitro transcriptomic responses to PNX-20, A8535, and PT-91 in the ovaries of three fishes with different SREB systems: 1) zebrafish (Danio rerio) that exhibit similar receptors to mammals, 2) mummichog (Fundulus heteroclitus) that lost a receptor but gained a fish-specific member, and 3) pufferfish (Dichotomyctere nigroviridis) that exhibit all four receptors. Agonist interactions with fish SREB1s were confirmed using in silico characterizations. Zebrafish exhibited the strongest transcriptome response, including agonist-induced changes in oxidative phosphorylation and cell adhesion pathways. Mummichog exhibited a less robust response, possibly related to receptor evolutionary divergence, while pufferfish exhibited an intermediate transcriptome response. Short-term agonist exposure did not alter ovarian steroid levels ((17)estradiol, 17-hydroxyprogesterone, cortisol, testosterone, or 11-ketotestosterone). Collectively, the data reveal previously unrecognized developmental, metabolic, neural, and vascular gene networks associated with SREB activation and suggest both receptor-specific signaling and functional overlap within this family.

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Идентификаторы

DOI: 10.1210/endocr/bqag089

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