Bioassay for identifying ligands for steroid hormone receptors

Abstract

Bioassays are disclosed which are useful for determining whether a compound is a hormone receptor agonist (i.e., is capable of promoting the transcription-activation activities of such receptors) or a hormone receptor antagonist (i.e., is capable of blocking the transcription-activation activities of such receptors). The invention bioassay is conducted by culturing test cells in the presence of at least one compound whose ability to function as a ligand for said receptor protein (or functional engineered or modified forms thereof) is sought to be determined. Alternatively, test cells are cultured in medium containing increasing concentrations of at least one compound whose ability to inhibit the transcription activation activity of hormone receptor agonists is sought to be determined, and a fixed concentration of at least one agonist for the receptor protein. Test cells employed in the practice of the present invention contain non-endogenous DNA which expresses hormone receptor (or functional modified forms thereof) and a DNA sequence encoding a hormone response element operatively linked to a reporter gene. The cultured cells are monitored for evidence of transcription of the reporter gene as a function of the concentration of test compound in the culture medium. The variation in transcription levels of the reporter gene as a function of concentration of test compound indicates the ability of test compound to promote or inhibit activation of transcription.