Progesterone ReceptorEndocrine disruption: Estimation of the binding affinity of small molecules towards the Progesterone receptor.
Estrogen and progesterone are two female reproductive hormones that have effects on multiple organs beyond reproductive system. Their actions are mediated through receptor-based gene stimulation. The progesterone receptor (PR) is a member of the nuclear receptor (NR) superfamily that includes the androgen (AR), estrogen (ERαβ), glucocorticoid (GR), and mineralocorticoid (MR) receptors. Two different isoforms, PRα and PRβ were identified in various organs targeted by progesterone. It has been observed that PRβ acts mainly as progesterone-responsive gene activator, whereas PRα functions as a modulator of the PRβ activity and repressor for other NRs, suggesting that PRα is an important modulator for steroid hormone receptor actions. Primary targets of PR agonist and antagonist combined with estrogen are hormonal birth control, hormone replacement therapy, endometriosis, dysfunctional uterine bleeding, dysmenorrhoea, endometrial cancer, uterine leiomyomas, breast cancer and meningiomas. Focus on development of more selective and efficacious PR modulators, including both agonists and antagonists, have increased to a great extent considering the unwanted effects due to affinities towards other NRs (AR, GR, ERαβ, MR) and the GABA (γ-amino butyric acid) receptor.
Binding of Mifepristone to the progesterone receptor as identified through automated, flexible docking.
Comparison of experimental and predicted Ki values for the progesterone receptor
(training set = black, test set = red).