EFFECTS OF ANTIPROGESTERONE MURINE MONOCLONAL-ANTIBODIES ON PLASMA PROGESTERONE CONCENTRATIONS AND ON ANTI-MOUSE REACTIONS IN CYCLIC PIGS

The effect of murine anti-progesterone monoclonal antibodies on plasma progesterone levels was studied in cyclic gilts. Intravenous injectio n of increasing amounts of anti-progesterone antibodies (50-500 mg IgM ) resulted in a concomitant rise in levels of antibody-bound progester one (6-25 ng ml-1). At the same time a significant rise in plasma conc entrations of total progesterone (3-21 ng ml-1) was observed immediate ly after the administration of antibodies. The net effect of progester one binding by the monoclonal antibody on circulating progesterone lev els was significant for the group of animals injected with at least 50 mg of antibody. The effect, however, was relatively small (1-11 ng ml -1) and more or less independent of the quantities of antibody adminis tered. Plasma levels of circulating antibody capable of binding proges terone were still detectable at the end of the experimental period (+/ - 13 days after injection). On the other hand, it appeared that in all animals, except the one injected with the largest quantity (500 mg) o f antibody, the concentration of antibody-bound progesterone started t o decrease as early as the first day after injection and was below det ectable levels within 1 or 2 days. Mechanisms that may control the ini tial increase in progesterone levels and enable the animals to maintai n adequate levels of free progesterone in circulation are discussed. A dministration of a minimum dose of 32 mg antibody resulted in an anti- mouse immune response after the first injection, and subsequently in a neutralization of the anti-progesterone monoclonal antibodies immedia tely after the second injection. When smaller quantities of antibody ( less-than-or-equal-to 20 mg) were used, anti-mouse antibodies were det ected only after the second or third injection.