Diethylstilbestrol selectively modulates plasma coagulation protein
synthesis by the perfused rat liver
MR Owens and CD Cimino
The combined effects of orchiectomy and estrogen administration on
synthesis of selected hepatic secretory proteins--antithrombin (AT) III,
plasminogen, fibrinogen, factor II (prothrombin), factor VII, fibronectin,
and albumin--were studied using the isolated rat liver perfused in vitro
for ten hours. Male rat liver donors underwent orchiectomy under ether
anesthesia and then received 5.0 mg of diethylstilbestrol (DES) by
subcutaneous pellet implantation or a placebo pellet; 14 days later the
livers were extracted and perfused in vitro for ten hours. In DES
experiments, 1.0 mg of DES was also added directly to the liver perfusate
at the outset. Pretreatment with DES resulted in significant increases in
cumulative synthesis of factors II (65%) and VII (76%) and significant
reduction in cumulative synthesis of both antithrombin III (20%; P = .03)
and plasminogen (27%; P less than .01) compared to control perfusions, but
synthesis of fibrinogen, fibronectin, and albumin was not significantly
affected by addition of the hormone. Plasma samples collected from rat
liver donors that had received DES showed similar effects on protein
concentrations: significant decreases in concentration of plasminogen and
antithrombin III were apparent with no significant changes in
concentrations of fibrinogen, fibronectin, or albumin. In additional
perfusions, "dose- response" experiments were conducted in which rat liver
donors received a subcutaneous DES pellet of 0.5, 5.0, or 50 mg. Synthesis
of plasminogen in this group of perfusions was progressively decreased as
the concentration of DES administered to the rat liver donor increased.
Synthesis of AT III was reduced to the same degree by 5.0 or 50 mg of DES,
both being substantially lower than the 0.5-mg experiments. Concentrations
of these two proteins in plasma samples from rat liver donors showed
changes quite similar to those seen in perfusion experiments; however,
plasma fibrinogen concentrations were not different among the three groups
of rats.
Volume 66,
Issue 2,
pp. 402-406,
08/01/1985
Copyright © 1985 by The American Society of Hematology
