The Syrian hamster has a peculiar sex limited serum protein, expressed as a major protein in females (therefore called Female Protein) and testosterone suppressed in males. Female Protein (FP) is a homolog of two human pentraxins, C-reactive protein (CRP) and serum amyloid P component (SAP) as shown by similar structure (pentameric) and amino acid sequence. Furthermore, FP shares function-properties with both human pentraxins such as Ca++ dependent phosphorylcholine binding, complement fixation, acute phase responsiveness (characteristics of CRP) and also is a constituent of amyloid (characteristic of AP). Indeed, high serum levels of FP occurring naturally (as in female) or experimentally (as in hormonally treated male) are directly associated with deposition of amyloid. We have obtained further information which indicates that high serum levels of FP are a primary cause of hamster amyloidosis. Thus, females treated with testosterone to lower serum FP levels do not acquire amyloidosis as early in life as do normal hamster females. Also, down regulation of FP synthesis in female hamsters was associated with enhanced longevity, as female hamsters typically die of amyloidosis. Estrogen administered to male hamsters enhances expression of amyloidosis; however, only those estrogens which increase FP synthesis (such as diethylstilbestrol) will have this effect. Also, this amyloid enhancing effect of diethylstilbestrol can be inhibited by concomitant testosterone injections, a regime which inhibits FP synthesis. The sex hormone control of FP synthesis in the Syrian hamster provides a unique opportunity to examine the role of this pentraxin in amyloidosis and to show that in this one model the P component homolog is of primary importance in the deposition of amyloid. FP synthesis is under different control mechanism in other hamsters, for example, in Armenian hamster, FP is down regulated by estrogen administration; estrogen also induces an unusual acute hepatotoxicity in Armenian hamster and after 3 to 5 months, hepatocellular carcinomas are found in these estrogen treated animals. Induction of liver cancer by estrogen alone is unusual, and we are continuing our studies on the possible role of FP in this unique animal model of estrogen induced liver toxicity and cancer.
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