Methods of using the A form of the progesterone receptor to screen for antagonists of steroid intracellar receptor-mediated transcription

A method for screening for antagonists of steroid intracellular receptor-mediated transcription comprising:

• (a) providing a cell comprising asteroid intracellular receptor other than progesterone receptor, progesterone receptor A form and a reporter vector, wherein the progesterone receptor A form is a negligible activator of transcription in the cell, and wherein the reporter vector includes a gene encoding a reporter product and a promoter which is transcriptionally active in the presence of the steroid intracellular receptor and an activator of said steroid intracellular receptor-mediated transcription, but is a negligible activator of transcription in the presence of the progesterone receptor A form;
• (b) contacting the cell with the activator of steroid intracellular receptor-mediated transcription and a second compound;
• and
• (c) comparing the level of reporter product expressed in the cell relative to the level of reporter product expressed in a second cell containing the steroid intracellular receptor and reporter vector, and contacted with the activator and second compound, as an indication of the potential antagonist activity of the second compound on steroid intracellular receptor-mediated transcription.

A method for screening progesterone receptor agonist or antagonist for estrogen receptor antagonist activity comprising:

• (a) introducing a first vector encoding estrogen receptor and a second vector encoding progesterone receptor A form along with a third reporter vector into a cell in which the progesterone receptor A form is a negligible activator of transcription, wherein the reporter vector includes a gene encoding a reporter product and a promoter which is transcriptionally active in the presence estrogen receptor but is a negligible activator of transcription in the presence of the progesterone receptor A form;
• (b) contacting the cell with an estrogen receptor agonist and a progesterone receptor agonist or antagonist;
• and
• (c) comparing the level of reporter product expressed in the cell relative to the level of reporter product expressed in a second cell containing estrogen receptor and the reporter vector, and contacted with the estrogen receptor agonist and progesterone receptor agonist or antagonist, as an indication of the potential antagonist activity of the progesterone receptor agonist or antagonist on estrogen receptor-mediated transcription.