Hamster female protein. A divergent acute phase protein in male and female Syrian hamsters.

Abstract

Acute phase proteins are serum constituents that change in concentration after injury. This acute phase reaction may result in decreased serum levels (albumin), or more frequently, a 50-300% increased serum level (Ca or haptoglobin) (1, 2). Human C-reactive protein (CRP) x is the classic acute phase reactant, its level increasingas much as 500-fold after injury (for review see reference 3). The beneficial effects of CRP in the inflammatory response are unknown although CRP can initiate or modulate a variety of biological events (4). Furthermore, CRP has evolved conservatively, insofar as homologous proteins with similar functional attributes have been found in many other species: the stable preservation of this protein during evolution implies some biological importance (5). In general, CRP homologs are present at relatively low serum levels, and sex of the species has little influence on normal content or acute phase changes after injury. A serum protein homologous to CRP has been described in the Syrian hamster. This protein, called female protein (FP) (6), has structural and functional features in common with CRP (7). However, FP is an unusual homolog because it is a prominent serum protein in females (1-2 mg/ml), and because its expression is sex limited, normal males having low serum levels (6).In the present report, the capacity of FP to respond as an acute phase protein was examined in male and female Syrian hamsters. The results indicated a divergent sexlimited acute phase response, characterized by increased FP serum levels in males and a transient decrease in females. When male/female FP levels were inversed by hormonal manipulation, a corresponding change in acute phase response also occurred, so that the pattern of response was related to high or low serum FP concentration rather than gender per se. Studies with 125I-FP indicated a similar catabolism of FP in both sexes under normal conditions and during acute phase changes; therefore, the variations in FP levels primarily reflect differences in rate of FP synthesis rather than degradation. Materials and MethodsAnimals. Random bred and inbred (LCH) Syrian hamsters were obtained from the Rocky Mountain Laboratories' hamster colony. Animals were fed Purina laboratory chow and water ad lib. Hamsters injected with 125I-FP received 0.1% KI in drinking water before and during the experiment.Antisera and Protein Purification. Rabbit antisera specific for FP and its use for ring diffusion quantification were previously described (6, 7). Hamster serum albumin was quantified by ring 1 Abbreviations used in this paper: AP, amyloid P component; CRP, C-reactive protein; FP, female protein; PAGE, polyacrylamide gel electrophoresis; PC, phosphorylcholine; T1/2, half-life; To, 5 rain after injection.

Hamster female protein, a sex-limited pentraxin, is a constituent of Syrian hamster amyloid.

“…Injecting males with another estrogen (estradiol) also has resulted in increased serum FP levels and detectable amyloid (unpublished). Na caseinate injection of male hamsters results in moderately elevated FP levels (unpublished), which is not surprising considering that serum levels of FP increase as an acute phase protein in males (15). Therefore, predisposition for amyloid formation appears to correlate with high serum levels of FP present normally (as in female) or artificially induced (as in DES male).…”

“…Treatments consisted of (a) a single diethylstilbestrol (DES) 12-mg pellet (Pfizer Inc., New York) surgically implanted subcutaneously every 3-4 mo and (b) I ml of Na caseinate (Difco Laboratories, Detroit, MI, 12.5% sterile) injected subcutaneously three times per week. Amyloid was also observed after injection of turpentine (15). Livers of pentobarbital anesthetized hamsters were perfused in situ with saline (50 ml) by passing a cannula into the inferior vena cava and cutting the portal veins.…”

“…Randomly bred Syrian hamsters (Mesocricetus auratus) were obtained from the Rocky Mountain Laboratories hamster colony and maintained as before (15).…”

“…Isolated FP and DEAE-purified rabbit gamma globulin (RGG) were iodinated with "25I (New England Nuclear, Boston, MA) as previously described (15 …”

“…This has resulted in an unprecedented high concentration of this pentraxin in serum of female hamsters (1-2 mg/ml), whereas normal males have levels -100-fold less as a result of testosterone suppression. Pentraxins of man and other mammals are known to increase serum levels during an acute phase response; however, a unique divergent response occurs in the hamster in which serum FP increases in male and decreases in female (15). Although the amino acid sequence at the NH2 terminus of FP is more similar to human SAP (identity at 19 of 23 residues) than to human CRP (13), hamster FP does exhibit a Ca+-dependent phosphorylcholine (PC)-binding capacity and does activate complement at the level of Cl (Etlinger, H. M., and J. E. Coe, submitted for publication).…”