Fr. Tekpetey et Dt. Armstrong, CATECHOLESTROGEN MODULATION OF STEROID-PRODUCTION BY RAT LUTEAL CELLS- MECHANISM OF ACTION, Molecular and cellular endocrinology, 101(1-2), 1994, pp. 49-57
This study investigated the mechanisms underlying 2-hydroxyestradiol (
2-OHE(2)) effect on luteal steroidogenesis using serum-free cultures o
f mixed luteal cells from day 8 pseudopregnant rats. Initially, intera
ctions between 2-OHE(2) and LH or dibutyryl (db)cAMP on progesterone p
roduction were investigated. LH (2.50 ng/ml) and 2-OHE(2) (2.5 mu g/ml
) had comparable effects on progesterone accumulation, while dbcAMP (5
mM) was more stimulatory. When applied together, 2-OHE(2) did not syn
ergize with LH or dbcAMP to further enhance progesterone accumulation.
Furthermore, in time course experiments, the dose-dependent effect of
2-OHE(2) was to reduce and eventually abolish the time-dependent incr
ease in cAMP accumulation. In contrast LH stimulated cAMP accumulation
at all times. Experiments in which cells were co-treated with 2-OHE(2
), 22-OH-cholesterol and cyanoketone, or with 2-OHE(2) and 22-OH-chole
sterol or pregnenolone indicated that 2-OHE(2) not only had a stimulat
ory effect on the cholesterol side-chain cleavage and 3 beta-hydroxyst
eroid dehydrogenase enzymes, but it also appeared to inhibit the 20 al
pha-hydroxysteroid dehydrogenase leading to a relative increase in pro
gesterone accumulation. Experiments with hormone antagonists suggested
that the actions of 2-OHE(2) were not mediated by the estrogen, alpha
- or beta-adrenergic receptors. The results of this study support the
concept of a physiological role for catecholestrogens in rat luteal st
eroidogenesis.