Androgens are classically thought to act through intracellular androgen receptors (AR/NR3C4), but they can also trigger non-genomic effects via membrane proteins. Although several membrane androgen receptors have been characterized in vitro, their functions in vivo remain unclear. Using a chemical-genetic screen in zebrafish, we found that GPRC6A, a G-protein-coupled receptor, mediates non-genomic androgen actions during embryonic development. Exposure to androgens (androstanedione, DHT and testosterone) caused cardiac edema or tail curvature in wild-type embryos, as well as in ar mutants, suggesting AR-independent pathways. We then mutated putative membrane androgen receptors [gprc6a, hcar1-4 and zip9 (slc39a9)] and found that only gprc6a mutants exhibited a significant reduction in cardiac edema after testosterone exposure. Additionally, co-treatment of wild-type embryos with testosterone and GPRC6A antagonists significantly suppressed the cardiac edema phenotype. Using RNA-seq and RNA rescue approaches, we found that testosterone and GPRC6A cause cardiac phenotypes by reducing Pak1 signaling. Our results indicate that testosterone induces cardiac edema in zebrafish embryos through GPRC6A, independent of nuclear androgen receptors, highlighting a previously unappreciated non-genomic androgen signaling pathway in embryonic development.
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http://dx.doi.org/10.1242/dev.204390 | DOI Listing |
Int J Biol Macromol
December 2024
Applied Organic Chemistry Department, National Research Center, Dokki, Cairo 12622, Egypt; Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria, Canal El Mahmoudia St., Alexandria 21648, Egypt. Electronic address:
The current research focuses on the design and synthesis of celecoxib analogues incorporating sulphonamide pyrazole moieties 4, 5, 6a-e, and 7a-f with the aim of achieving a broad range of COX-2 selectivity in vitro. Among these, compounds 6b-d, 7a, 7e, and 7d exhibited potent inhibition, with IC values ranging between 0.05 and 0.
View Article and Find Full Text PDFDiseases
December 2024
Department of Neurology, "Victor Babes" University of Medicine and Pharmacy Timisoara, 300041 Timisoara, Romania.
Noncardiogenic pulmonary edema after cardiac surgery is a rare but severe complication. The etiology remains poorly understood; however, the issue may arise from multiple sources. Possible causes include a significant inflammatory response or an autoimmune process.
View Article and Find Full Text PDFChemosphere
December 2024
University of North Texas, Department of Biological Sciences and Advanced Environmental Research Institute, Denton, TX, 76203. Electronic address:
The goal of this study was to compare the bioaccumulation of the PCB mixture Aroclor 1254 in zebrafish to cardiac and neurologic outcomes. The establishment of effect concentrations (ECs) for cardiac and neurotoxic effects of PCBs in early life stage fish is challenging due to a lack of measured PCB concentrations in test media (e.g.
View Article and Find Full Text PDFJ Pediatr Hematol Oncol
December 2024
Division of Paediatric Cardiology.
Background: Burkitt's lymphoma (BL) is the most common subtype of non-Hodgkin lymphoma in children, typically presenting with extranodal masses in areas such as the abdomen, face, and neck. Cardiac involvement in BL is extremely rare, especially in pediatric patients, and has significant implications for diagnosis, management, and prognosis.
Case Presentation: A 6-year-old male patient with Burkitt's lymphoma, presenting with an uncommon infiltration of the interatrial septum, is described.
Sci Prog
December 2024
Cardiology and Internal Medicine Department, Fundación Clínica Shaio, Bogotá, Colombia.
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