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A Monoclonal Antibody to Progesterone Interrupts Pregnancy in the Hamster by Curtailing Secretion of the Luteotropic Complex of Prolactin and Follicle- Stimulating Hormone^*

GILBERT S. GREENWALD and MING-WEI WANG

Department of Physiology (G.S.G.), Uniuersity of Kansas Medical Center Kansas City, Kansas 66103;
AFRC Institute of Animal Physiology and Genetics Research (M. W, W) Babraham,Cambridge CB2 4AT, United Kingdom

Address all correspondence and requests for reprints to: Dr. Gilbert S. Greenwald, Department of Physiology, Ralph L. Smith Research Center, 39th and Rainbow Boulevard, Kansas City, Kansas 66103.

Abstract

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 dally 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, (Endocrinology 129: 1735–1743, 1991)

Footnotes

^* This work was supported by NIH Grant HD-00596 (to G.S.G.).

Present address: Amylin Corporation, 9373 Towne Centre Drive, Suite 250, San Diego, California 92121.

Received August 4, 1991.

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