Effects of 5α-reductase inhibition by dutasteride on reproductive gene expression and hormonal responses in zebrafish embryos
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 docum...
Gespeichert in:
| Hauptverfasser: | , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
January 2025
|
| In: |
Comparative biochemistry and physiology. Part C, Toxicology & pharmacology
Year: 2025, Jahrgang: 287, Pages: 1-124 |
| ISSN: | 1878-1659 |
| DOI: | 10.1016/j.cbpc.2024.110048 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.cbpc.2024.110048 Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1532045624002163 
|
| Verfasserangaben: | Hyunki Cho, Indong Jun, Karim Md Adnan, Chang Gyun Park, Sang-Ah Lee, Juyong Yoon, Chang Seon Ryu, Young Jun Kim |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1923962086 | ||
| 003 | DE-627 | ||
| 005 | 20250717012224.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 250429s2025 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1016/j.cbpc.2024.110048 |2 doi | |
| 035 | |a (DE-627)1923962086 | ||
| 035 | |a (DE-599)KXP1923962086 | ||
| 035 | |a (OCoLC)1528044965 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Cho, HyunKi |e VerfasserIn |0 (DE-588)1350887161 |0 (DE-627)1912184311 |4 aut | |
| 245 | 1 | 0 | |a Effects of 5α-reductase inhibition by dutasteride on reproductive gene expression and hormonal responses in zebrafish embryos |c Hyunki Cho, Indong Jun, Karim Md Adnan, Chang Gyun Park, Sang-Ah Lee, Juyong Yoon, Chang Seon Ryu, Young Jun Kim |
| 246 | 3 | 3 | |a Effects of 5alpha-reductase inhibition by dutasteride on reproductive gene expression and hormonal responses in zebrafish embryos |
| 264 | 1 | |c January 2025 | |
| 300 | |b Illustrationen | ||
| 300 | |a 12 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Online verfügbar: 21. September 2024, Dokumentversion: 26. September 2024 | ||
| 500 | |a Gesehen am 29.04.2025 | ||
| 520 | |a 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. | ||
| 650 | 4 | |a 5α-reductase inhibition | |
| 650 | 4 | |a Adverse outcome pathway | |
| 650 | 4 | |a Dihydrotestosterone | |
| 650 | 4 | |a Dutasteride | |
| 650 | 4 | |a Reproductive toxicity | |
| 650 | 4 | |a Zebrafish embryo | |
| 700 | 1 | |a Jun, Indong |e VerfasserIn |4 aut | |
| 700 | 1 | |a Adnan, Karim Md |e VerfasserIn |4 aut | |
| 700 | 1 | |a Park, Chang Gyun |e VerfasserIn |0 (DE-588)1343560012 |0 (DE-627)190371396X |4 aut | |
| 700 | 1 | |a Lee, Sang-Ah |e VerfasserIn |4 aut | |
| 700 | 1 | |a Yoon, Juyong |e VerfasserIn |4 aut | |
| 700 | 1 | |a Ryu, Chang Seon |e VerfasserIn |4 aut | |
| 700 | 1 | |a Kim, Young Jun |d 1976- |e VerfasserIn |0 (DE-588)141729872 |0 (DE-627)635532336 |0 (DE-576)330174592 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Comparative biochemistry and physiology. Part C, Toxicology & pharmacology |d New York, NY : Elsevier, 2001 |g 287(2025) vom: Jan., Artikel-ID 110048, Seite 1-124 |h Online-Ressource |w (DE-627)300185464 |w (DE-600)1481606-4 |w (DE-576)078941318 |x 1878-1659 |7 nnas |a Effects of 5α-reductase inhibition by dutasteride on reproductive gene expression and hormonal responses in zebrafish embryos |
| 773 | 1 | 8 | |g volume:287 |g year:2025 |g month:01 |g elocationid:110048 |g pages:1-124 |g extent:12 |a Effects of 5α-reductase inhibition by dutasteride on reproductive gene expression and hormonal responses in zebrafish embryos |
| 856 | 4 | 0 | |u https://doi.org/10.1016/j.cbpc.2024.110048 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://www.sciencedirect.com/science/article/pii/S1532045624002163 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20250429 | ||
| 993 | |a Article | ||
| 994 | |a 2024 | ||
| 998 | |g 1343560012 |a Park, Chang Gyun |m 1343560012:Park, Chang Gyun |d 910000 |d 911200 |e 910000PP1343560012 |e 911200PP1343560012 |k 0/910000/ |k 1/910000/911200/ |p 4 | ||
| 999 | |a KXP-PPN1923962086 |e 4716000095 | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"origin":[{"dateIssuedKey":"2025","dateIssuedDisp":"January 2025"}],"name":{"displayForm":["Hyunki Cho, Indong Jun, Karim Md Adnan, Chang Gyun Park, Sang-Ah Lee, Juyong Yoon, Chang Seon Ryu, Young Jun Kim"]},"titleAlt":[{"title":"Effects of 5alpha-reductase inhibition by dutasteride on reproductive gene expression and hormonal responses in zebrafish embryos"}],"recId":"1923962086","id":{"eki":["1923962086"],"doi":["10.1016/j.cbpc.2024.110048"]},"physDesc":[{"noteIll":"Illustrationen","extent":"12 S."}],"language":["eng"],"note":["Online verfügbar: 21. September 2024, Dokumentversion: 26. September 2024","Gesehen am 29.04.2025"],"title":[{"title":"Effects of 5α-reductase inhibition by dutasteride on reproductive gene expression and hormonal responses in zebrafish embryos","title_sort":"Effects of 5α-reductase inhibition by dutasteride on reproductive gene expression and hormonal responses in zebrafish embryos"}],"relHost":[{"origin":[{"dateIssuedDisp":"2001-","publisherPlace":"New York, NY ; London [u.a.]","publisher":"Elsevier ; Pergamon Press","dateIssuedKey":"2001"}],"recId":"300185464","name":{"displayForm":["Division of Comparative Physiology, American Society of Zoologists"]},"titleAlt":[{"title":"Comparative biochemistry and physiology / Part C"},{"title":"CBP"},{"title":"Toxicology and pharmacology"}],"physDesc":[{"extent":"Online-Ressource"}],"id":{"zdb":["1481606-4"],"issn":["1878-1659"],"eki":["300185464"]},"language":["eng"],"note":["Gesehen am 03.06.2024"],"title":[{"partname":"Toxicology & pharmacology","title_sort":"Comparative biochemistry and physiology","subtitle":"CBP ; an international journal","title":"Comparative biochemistry and physiology"}],"pubHistory":["Volume 128, issue 1 (January 2001)-"],"part":{"year":"2025","extent":"12","text":"287(2025) vom: Jan., Artikel-ID 110048, Seite 1-124","volume":"287","pages":"1-124"},"type":{"bibl":"periodical","media":"Online-Ressource"},"disp":"Effects of 5α-reductase inhibition by dutasteride on reproductive gene expression and hormonal responses in zebrafish embryosComparative biochemistry and physiology. Part C, Toxicology & pharmacology"}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"person":[{"given":"HyunKi","role":"aut","roleDisplay":"VerfasserIn","display":"Cho, HyunKi","family":"Cho"},{"display":"Jun, Indong","family":"Jun","given":"Indong","role":"aut","roleDisplay":"VerfasserIn"},{"family":"Adnan","display":"Adnan, Karim Md","roleDisplay":"VerfasserIn","role":"aut","given":"Karim Md"},{"family":"Park","display":"Park, Chang Gyun","role":"aut","roleDisplay":"VerfasserIn","given":"Chang Gyun"},{"roleDisplay":"VerfasserIn","role":"aut","given":"Sang-Ah","family":"Lee","display":"Lee, Sang-Ah"},{"family":"Yoon","display":"Yoon, Juyong","role":"aut","roleDisplay":"VerfasserIn","given":"Juyong"},{"family":"Ryu","display":"Ryu, Chang Seon","roleDisplay":"VerfasserIn","role":"aut","given":"Chang Seon"},{"given":"Young Jun","roleDisplay":"VerfasserIn","role":"aut","display":"Kim, Young Jun","family":"Kim"}]} | ||
| SRT | |a CHOHYUNKIJEFFECTSOF52025 | ||