Down-Regulation of Endometrial Matrix Metalloproteinase-3 and -7 Expressionin Vitroand Therapeutic Regression of Experimental Endometriosisin Vivoby a Novel Nonsteroidal Progesterone Receptor Agonist, Tanaproget

Abstract

Given the positive preclinical pharmacological profile of TNPR that has recently been reported, additional development of this compound for the treatment of endometriosis is warranted.

Statins Inhibit Monocyte Chemotactic Protein 1 Expression in Endometriosis

“…10,17 Five-week-old ovariectomized female nude mice (NCr strain, n ¼ 15) were purchased from Harlan Sprague Dawley (Indianapolis, Indiana). After a 1-week acclimation period, mice were implanted with a slow-release silastic capsule containing 8 mg 17b-estradiol (in cholesterol) 24 hours before injection of human tissues.…”

Novel Therapies Targeting Endometriosis

“…25 Experimental endometriosis can also be established using tissues obtained via collection of menstrual effluent or from surgical specimens obtained from women with endometriosis. [26][27][28][29] Studies such as these have revealed important differences between eutopic endometrial tissues obtained from women with endometriosis compared to eutopic or ectopic tissues obtained from disease-free women. For example, we have demonstrated that endometrial tissues obtained from women with endometriosis exhibit a reduced response to progesterone which promotes the development of experimental endometriosis.…”

“…In contrast, progesterone therapy fails to prevent the establishment and progression of experimental endometriosis when xenografts are established with eutopic endometrial tissue obtained from women with endometriosis. 29,30 Therefore, we additionally examined whether a potent, nonsteroidal progesterone receptor agonist would have a better therapeutic profile compared to natural progesterone. In this study, Tanaproget, a selective progesterone receptor modulator developed by Wyeth Research (Collegeville, Pennsylvania), was found to be more effective than either progesterone or medroxyprogesterone acetate in reducing experimental endometriosis in our model when ectopic disease was established by eutopic endometrial tissues acquired from women with endometriosis.…”

Progesterone Resistance and Targeting the Progesterone Receptors: A Therapeutic Approach to Endometriosis

“…Whilst the evaluation of gene ablation on eutopic and ectopic endometrial cell growth has been revealing, the studies of pharmacological modulation contrast these observations to a certain extent as both progestogens and PRAs reduce ectopic endometrial cell proliferation and disease burden in pre-clinical rodent models of endometriosis (Bruner-Tran et al, 2006;Chwalisz et al, 1998;Katayama et al, 2010;Katsuki et al, 1998;Stoeckemann et al, 1995). An explanation of this phenomenon compared with the phenotype of PRKO animals has been revealed by studies with PRAs in the non-human primate.…”