Peer review of the Retinoic Acid Receptor Transactivation (RARTA) method validation

The retinoid acid receptors (RARs) are ligand-activated transcription factors of the nuclear receptor superfamily. RARs form heterodimers with Retinoid X Receptors (RXRs). The RARs-RXRs heterodimers are involved in a wide range of key physiological processes, including proper embryogenesis, differentiation, and growth arrest.

Once activated by a ligand, RXR-RARs are able to modulate the transcription of target genes. Because of the involvement of RARs in key physiological processes, it is important to assess the ability of chemicals to interfere with this specific nuclear receptor.

A stably transfected cell line HRLN expressing the reporter gene luciferase specifically activated by the RXR-RARs heterodimers in the presence of an effector ligand has been developed for this purpose. The HRL+N cell line expresses both retinoic acid receptors (RARα, β and γ) and retinoid X receptors (RXRα, β and γ). This cell line can be used in an in vitro transactivation assay for the evaluation of agonistic and antagonistic activity of chemicals towards human RARs or RXRs.

Currently, there is no Test Guideline assessing the effects of xenobiotics on this endocrine pathway. Following the peer review of the validation study and depending on its outcome, the objective of the project is to fill the gap and develop a Test Guideline for a Retinoic Acid Receptor Transactivation Assay.