Studies on the mechanism of action of oral contraceptives with regard to fibrinolytic variables.
Evidence is provided that the fibrinolytic capacity in plasma is strongly dependent on circulating concentrations of tissue plasminogen activator rather than on concentrations of plasminogen activator inhibitor. Thus a decrease in plasma tissue plasminogen activator concentrations, as is the case in oral contraceptive users, may result in a decrease in plasma fibrinolytic capacity despite a parallel decrease in plasminogen activator inhibitor levels. It is now clear that the presence of specific intracellular receptors and a given motif in the genome are essential to mediate hormone-dependent regulation of gene expression. A computer search revealed potential estrogen and glucocorticoid-progesterone-responsive elements in the genes coding for tissue plasminogen activator, plasminogen activator inhibitor, and some other fibrinolytic variables. No convincing evidence for the presence of sex steroid receptors in endothelial cells was found, but liver cells clearly contain estrogen and androgen receptors. However, neither endothelial cells nor hepatocytes cultured in vitro showed a change in tissue plasminogen activator or plasminogen activator inhibitor synthesis on incubation with sex steroids (10(-9) to 10(-6) mol/L) for 3 days. An alternative explanation for the observed decreases in tissue plasminogen activator and plasminogen activator inhibitor concentrations in the plasma of oral contraceptive users is discussed.
Kooistra
T
T
Gaubius Institute TNO, Leiden, The Netherlands.
Bosma
P J
PJ
Jespersen
J
J
Kluft
C
C
D003277:Contraceptives, Oral, Combined / Q000494:pharmacology*; D003278:Contraceptives, Oral, Hormonal / Q000494:pharmacology*; D004727:Endothelium / Q000187:drug effects; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000187:drug effects; D010959:Tissue Plasminogen Activator / Q000097:blood
D003277:Contraceptives, Oral, Combined; D003278:Contraceptives, Oral, Hormonal; D011956:Receptors, Cell Surface; D010959:Tissue Plasminogen Activator