EARLY-PREGNANCY FACTOR IN LIVER-REGENERATION AFTER PARTIAL-HEPATECTOMY IN RATS - RELATIONSHIP WITH CHAPERONIN-10

Early pregnancy factor is not only a product of dividing embryonic and neoplastic cells, as demonstrated previously, but also of normal prol iferating cells. Eight hours after partial hepatectomy in rats, early pregnancy factor was detected in serum. It rose to a peak by 48 hr. Ne utralization of early pregnancy factor in vivo by passive immunization with specific antibodies, 18 hr after partial hepatectomy, resulted i n a significant decrease in the uptake of [H-3]thymidine by the liver remnant, measured 4 to 6 hr later. These results suggest that during l iver regeneration, early pregnancy factor is essential to the sequence of events that culminates in DNA synthesis and cell division. Recentl y we purified early pregnancy factor from human platelets and determin ed by mass spectrometry a precise molecular mass of 10,843 Da. Amino a cid sequencing (similar to 72% of the molecule) demonstrated that earl y pregnancy factor is highly homologous with chaperonin 10, a stress-i nducible mitochondrial protein, and that platelet-derived early pregna ncy factor and rat chaperonin 10 share similar biochemical and immunol ogical properties. In this study we show that early pregnancy factor, purified from regenerating rat liver and from serum taken 24 hr after hepatectomy, shares these properties. In addition, antibodies to early pregnancy factor, effective in passive immunization studies, recogniz e chaperonin 10, whereas chaperonin 10 antibodies bind to early pregna ncy factor from regenerating liver and posthepatectomy serum. We propo se that early pregnancy factor/chaperonin 10 is selectively released f rom proliferating cells and, in an autocrine or paracrine mode (or bot h) is involved in DNA synthesis.