MYOMETRIAL ESTROGEN AND PROGESTERONE-RECEPTOR BINDING IN PREGNANCY - INHIBITION BY THE DETERGENT ACTION OF PHOSPHOLIPIDS

We characterized the phospholipid inhibition of estradiol and progeste rone binding to guinea-pig and human myometrial receptors. Of twelve c ompounds studied, phosphatidylinositol (PI), lysophosphatidic acid and lysophosphatidylcholine (lyse-PC) were the most active inhibitors (50 % inhibition at 10(-5) M). Lyso-PC with fatty acid chain length C14:0 inhibited ligand binding both to estrogen receptor (ER) and progestero ne receptor (PR), C16:0 only to PR and C18:0 neither to ER nor to PR. The lyso-derivates were more inhibitory than the parent compounds. The ionic detergent (sodium taurocholate) inhibited both ER and PR bindin g, but the non-ionic detergent (Triton X-100) only PR. Triton X-100 en hanced the PI-induced inhibition of ER binding by a factor of 10. PR w as more sensitive to inhibition than ER in all cases. The type of inhi bition was non-competitive. At term pregnancy, ligand binding to myome trial ER or PR was low or absent in humans, but moderate in the guinea -pig. Phospholipid extracts of human decidua and fetal membranes conta ined PI and phosphatidylserine rather than lyso-PC. The extract was a potent inhibitor of ligand binding to PR (50% inhibition at 10(-6) M p hospholipid phosphorus), but not to ER. The physicochemical environmen t, modulated by phospholipids acting as detergents, may regulate sex s teroid function also in vivo. This might have special significance for pregnancy maintenance.