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Verfasst von:Cho, HyunKi [VerfasserIn]   i
 Jun, Indong [VerfasserIn]   i
 Adnan, Karim Md [VerfasserIn]   i
 Park, Chang Gyun [VerfasserIn]   i
 Lee, Sang-Ah [VerfasserIn]   i
 Yoon, Juyong [VerfasserIn]   i
 Ryu, Chang Seon [VerfasserIn]   i
 Kim, Young Jun [VerfasserIn]   i
Titel:Effects of 5α-reductase inhibition by dutasteride on reproductive gene expression and hormonal responses in zebrafish embryos
Verf.angabe:Hyunki Cho, Indong Jun, Karim Md Adnan, Chang Gyun Park, Sang-Ah Lee, Juyong Yoon, Chang Seon Ryu, Young Jun Kim
E-Jahr:2025
Jahr:January 2025
Umfang:12 S.
Illustrationen:Illustrationen
Fussnoten:Online verfügbar: 21. September 2024, Dokumentversion: 26. September 2024 ; Gesehen am 29.04.2025
Titel Quelle:Enthalten in: Comparative biochemistry and physiology. Part C, Toxicology & pharmacology
Ort Quelle:New York, NY : Elsevier, 2001
Jahr Quelle:2025
Band/Heft Quelle:287(2025) vom: Jan., Artikel-ID 110048, Seite 1-124
ISSN Quelle:1878-1659
Abstract:Steroid 5α-reductase (SRD5A) is a crucial enzyme involved in steroid metabolism, primarily converting testosterone to dihydrotestosterone (DHT). Dutasteride, an inhibitor of SRD5A types 1 and 2, is widely used for treating benign prostatic hyperplasia. An adverse outcome pathway (AOP) has been documented wherein SRD5A inhibition decreases DHT synthesis, leading to reduced levels of 17β-estradiol (E2) and vitellogenin (VTG), subsequently impairing fecundity in fish (AOP 289). However, the molecular and cellular mechanisms underlying these effects remain poorly understood. In this study, we assessed the impact of SRD5A inhibition on zebrafish embryos (Danio rerio). Exposure to dutasteride resulted in decreased DHT, E2, and VTG levels, showing a positive correlation. Dutasteride also downregulated the expression of reproduction-related genes (srd5a2, cyp19a1, esr1, esr2a, esr2b, and vtg), with interrelated reductions observed across these levels. Docking studies suggested that dutasteride's effects may operate independently of androgen receptor (AR) and estrogen receptor (ER) interactions. Furthermore, co-exposure of dutasteride (0.5 or 2 μM) with 0.5 μM DHT revealed gene expression levels comparable to the control group. These findings underscore DHT's pivotal role in modulating estrogenic function and the interplay between estrogenic and androgenic responses in vertebrates. Our proposed AOP model offers insights into mechanistic gaps, thereby enhancing current understanding and bridging knowledge disparities.
DOI:doi:10.1016/j.cbpc.2024.110048
URL:Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.

Volltext: https://doi.org/10.1016/j.cbpc.2024.110048
 Volltext: https://www.sciencedirect.com/science/article/pii/S1532045624002163
 DOI: https://doi.org/10.1016/j.cbpc.2024.110048
Datenträger:Online-Ressource
Sprache:eng
Sach-SW:5α-reductase inhibition
 Adverse outcome pathway
 Dihydrotestosterone
 Dutasteride
 Reproductive toxicity
 Zebrafish embryo
K10plus-PPN:1923962086
Verknüpfungen:→ Zeitschrift

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