Possible Interaction: Tissue Plasminogen Activator and Progesterone

“However, Northern blotting analysis demonstrated that progesterone strongly down-regulated (up to 60-fold) the gene expression of urokinase plasminogen activator and increased (up to 5-fold) the expression of tissue-type plasminogen activator in these cells.”

“The phorbol ester TPA , and basic fibroblast growth factor, dramatically suppress cAMP-induced production of progesterone , whereas bovine corneal endothelial cell ECM (BCE/ECM) enhanced cAMP-induced progesterone and antagonized basic fibroblast growth factor suppression of cAMP-induced steroidogenesis.”

“Blockade of progesterone signaling by TPA for 24 h results in fewer cells in G2/M, attributable to decreased expression of genes that facilitate the G2/M transition.”

“Gene expression data suggest that TPA affects several mechanisms that progesterone utilizes to control gene expression, including specific post-translational modifications, and nucleosomal organization and higher order chromatin structure, which regulate access of PR to its DNA binding sites.”

“Various agents that stimulate cellular protein phosphorylation (8-Br cAMP, okadaic acid, TPA ) functionally synergize with progesterone to enhance progesterone-dependent PRtrans-activation in intact cells.”

“Conversely, progesterone withdrawal reduces TF and PAI-1 expression and increases tPA , uPA, MMP, and ET-1 expression accounting for the hemorrhage, enhanced fibrinolysis, ECM degradation, and ischemic spiral arterial vascular injury characterizing menstruation.”

“In a primary human … culture, the addition of progesterone resulted in an approximately 2-… in the amount of tissue-type plasminogen activator (t-PA) released into the culture media, with the minimal effective dose being 10(-…. In contrast, progesterone significantly reduced the release of urokinase-type PA (u-PA).”

“In addition, while TPA inhibited the PMSG and forskolin induced-accumulation of progesterone in the media, the gonadotropin and forskolin inhibited the elevation of PGE2 levels evoked by TPA (a dose dependent decrease of 35-55%).”

“The study concluded that PROG may extend the time window for tPA administration in ischemic stroke and reduce hemorrhagic conversion.”

“Moreover, this response was inhibited by the PKC inhibitor H7, the PKCα specific inhibitor Gö‐6976 and the … cycloheximide, but not by the transcription inhibitor actinomycin D or the replication inhibitor mitomycin C. In addition, TPA also reversed the MMP‐… expression after by progesterone pretreatment in the … decidual cells.”

“Co-treatment with forskolin and TPA decreased progesterone and P450scc mRNA levels as compared to forskolin treatment alone.”