ABORTIFACIENT EFFECTS IN THE PREGNANT HAMSTER OF AN ANTIBODY TO PROGESTERONE ARE REVERSED BY EXOGENOUS PROLACTIN

A single i.p. injection of 10 nmol of a monoclonal antibody to progest erone (mAb-P-4) on Day 4 of pregnancy (day of nidation) interrupts pre gnancy by Day 8 (Day 1 = sperm-positive smear) in 75% of treated hamst ers (n = 8). This correlates with structural and functional luteolysis , significantly (p < 0.05) reduced serum prolactin (PRL), and a nonsig nificant trend for reduced FSH (which constitute the minimal luteotrop ic complex of the hamster), but LH is unchanged. Embryos implant and d evelop normally for a while, but by Day 8 the uterus is distended with the resorbing products of conception. The abortifacient effects of pa ssive immunization against progesterone are reversed 100% by s.c. inje ction of 100 mu g PRL daily on Days 4-7; deferring PRL treatment until Days 6-7 maintained pregnancy in 75% of the animals, still significan tly different from the untreated mAb-P-4 group. Injection of 50 mu g P RL on Days 4-7 maintains pregnancy in 50% of the mAb-P-4-treated hamst ers (not significantly different), whereas 10 mu g PRL on Days 4-7 is wholly ineffective. No dose of FSH (0.1-10.0 mu g) or LH (0.4-2.0 mu g ) on Days 4-7 reversed the effects of mAb-P-4; neither did 10 mu g PRC plus 0.4 or 2 mu g of FSH. The maintenance of pregnancy after 100 mu g PRC on Days 4-7 is associated with normal serum levels of PRL, FSH, and LH and no change in the serum concentration of the mAb-P-4 antibod y. The fall in serum FSH after injection of mAb-P-4 is the result of a ccelerated follicular growth at the onset of luteolysis; the follicles in vitro secrete progressively higher levels of inhibin on Days 6, 7, and 8 of pregnancy. Thus, the trend for the decline in FSH is most li kely a secondary event. The primary event therefore appears to be disr uption of a positive feedback loop of the hypothalamic-pituitary-ovari an axis. As free (non-antibody bound) P-4 drops to undetectable levels , PRL secretion is lowered, and one of the principal luteotropins is w ithdrawn. In this animal model, mAb-P-4 therefore does not act directl y at the uterine level.