Definition of the critical cellular components which distinguish between hormone and antihormone activated...

The steroid hormone progesterone is a key modulator of the cellular processes associated with the maintenance and development of female reproductive function. The biological activity of this hormone is mediated by specific nuclear receptors located in target cell nuclei which upon activation are capable of modulating the transcriptional activity of promoters containing progesterone response elements. Abnormalities in the progesterone receptor (PR) signal transduction pathway are implicated in pathological states such as breast cancer, endometriosis, and uterine fibroids. As a result of the medical need to modulate PR transcriptional activity, antiprogestins, compounds which oppose the actions of progesterone and novel progesterone receptor agonists, have been developed. This review outlines our current understanding of the critical cellular components which define the pharmacology of progesterone receptor agonists and antagonists, and how this information will impact the discovery and development of additional therapeutics.