A Multiwell-Based Assay for Screening Thyroid Hormone Signaling Disruptors Using thibz Expression as a Sensitive Endpoint in Xenopus laevis .

Publisher: MDPI Country of Publication: Switzerland NLM ID: 100964009 Publication Model: Electronic Cited Medium: Internet ISSN: 1420-3049 (Electronic) Linking ISSN: 14203049 NLM ISO Abbreviation: Molecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, c1995-

Endocrine Disruptors/*pharmacology ; Gene Expression/*drug effects ; High-Throughput Screening Assays/*methods ; Signal Transduction/*drug effects ; Thyroid Hormones/*metabolism; Alanine/analogs & derivatives ; Alanine/pharmacology ; Animals ; Halogenated Diphenyl Ethers/pharmacology ; Triiodothyronine/pharmacology ; Xenopus laevis

There is a need for rapidly screening thyroid hormone (TH) signaling disruptors in vivo considering the essential role of TH signaling in vertebrates. We aimed to establish a rapid in vivo screening assay using Xenopus laevis based on the T3-induced Xenopus metamorphosis assay we established previously, as well as the Xenopus Eleutheroembryonic Thyroid Assay (XETA). Stage 48 tadpoles were treated with a series of concentrations of T3 in 6-well plates for 24 h and the expression of six TH-response genes was analyzed for choosing a proper T3 concentration. Next, bisphenol A (BPA) and tetrabromobisphenol A (TBBPA), two known TH signaling disruptors, were tested for determining the most sensitive TH-response gene, followed by the detection of several suspected TH signaling disruptors. We determined 1 nM as the induction concentration of T3 and thibz expression as the sensitive endpoint for detecting TH signaling disruptors given its highest response to T3, BPA, and TBBPA. And we identified betamipron as a TH signaling agonist, and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) as a TH signaling antagonist. Overall, we developed a multiwell-based assay for rapidly screening TH signaling disruptors using thibz expression as a sensitive endpoint in X. laevis .

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2018YFA0901103 National Key Research and Development Program of China; 21876196 National Natural Science Foundation of China

Keywords: Xenopus laevis; multiwell plate; screening assay; thibz gene; thyroid hormone

0 (Endocrine Disruptors)
0 (Halogenated Diphenyl Ethers)
0 (Thyroid Hormones)
06LU7C9H1V (Triiodothyronine)
0N97R5X10X (2,2',4,4'-tetrabromodiphenyl ether)
2198-64-3 (N-benzoylalanine)
OF5P57N2ZX (Alanine)

Date Created: 20220215 Date Completed: 20220225 Latest Revision: 20220225

20231215

PMC8838645

10.3390/molecules27030798

35164063