Two
estrogen antagonists (
keoxifene and
clomiphene) and two
aromatase inhibitors (
LY56110 and 4-hydroxyandrostenedione, 4-OHA) were utilized to determine the role of conceptus
estrogen in trophoblastic elongation and maintenance of pregnancy in the pig. Pregnant gilts were unilaterally hysterectomized on day 10.5, and infused via a uterine arterial
catheter with 200 mg of
keoxifene or vehicle. The remaining uterine horn was removed based on time estimated for conceptus elongation. In a second study, pregnant gilts were injected daily with 200 mg (i.m.) of
clomiphene or vehicle during pregnancy (days 10-16) and hysterectomized on day 30. A third study assessed in vitro
aromatase inhibition by
4-OHA and
LY56110 using trophoblastic microsomes incubated with [1 beta, 2 beta-3H]-
androstenedione for 6 hr. In a fourth study, in vivo inhibition of
aromatase activity was determined. For this study pregnant gilts, unilaterally hysterectomized on day 10.5, received either
4-OHA,
LY56110, or vehicle. Conceptus development and uterine
estrogens were quantified. None of the
estrogen antagonists and
aromatase inhibitors interferred with conceptus elongation. Uterine
protein,
calcium and
acid phosphatase were similar (P greater than .10) between
keoxifene- and vehicle-treated gilts. Embryonic survival of
clomiphene- and vehicle-treated gilts was similar (91.5 vs 87.4%). In vitro,
4-OHA and
LY56110 had 50% inhibitory concentrations of 0.1 microM and 13 nM. Treatment of gilts with
4-OHA reduced total
estrogens in uterine
flushings by 57% (P less than .02), whereas treatment with
LY56110 did not significantly lower total
estrogen content in uterine
flushings.
Estrogen antagonists were not effective in blocking conceptus elongation and maintenance of pregnancy. Although
estrogen synthesis can be inhibited in vitro, dosages of
aromatase inhibitors used were not totally effective in vivo.