A MONOCLONAL-ANTIBODY TO PROGESTERONE INTERRUPTS PREGNANCY IN THE HAMSTER BY CURTAILING SECRETION OF THE LUTEOTROPHIC COMPLEX OF PROLACTIN AND FOLLICLE-STIMULATING-HORMONE

A single ip injection of 6.5 nmol of a monoclonal (immunoglobulin G) antibody to progesterone (MAB-P4), administered on the morning of implantation (day 4), interrupted pregnancy by day 8 in 75% of treated hamsters. Pregnancy was unaffected until day 6 although histologically, the embryos contained very few mitotic figures. However, by day 7, the swellings began to regress and were completely eliminated by day 8. The onset of embryonic reabsorption coincides with a drastic fall in free (nonantibody-bound) serum progesterone (P4), in vitro production of P4, and in vitro and in vivo increases in estradiol. The effects of MAB-P4 are completely reversible by a concurrent injection of 1 mg P4 on day 4, whereas deferred injection of P4 to day 6 is ineffective. The onset of functional and structural luteolysis is paralleled by a significant decline in the minimal luteotropic complex of PRL and FSH but with no change in LH. The effects of MAB-P4 are partially reversible by daily injection of FSH or PRL but not LH. We interpret these results as follows: normally during early pregnancy in the hamster endogenous P4 positively reinforces secretion of the luteotropic complex. MAB-P4 with its long half-life of 69 h binds serum P4 and therefore reduces circulating levels of free P4. Consequently, the secretion of PRL and FSH is curtailed without affecting LH. Thus, in the hamster when 6.5 nmol MAB-P4 is injected on day 4, the deprivation of P4 at the uterine level appears to be a secondary event to functional and structural luteolysis.