Syrian hamsters have a remarkable serum protein called female protein (FP) that is controlled by sex hormones. FP is preferentially expressed in female hamsters that normally have 2-3 mg FP/ml serum, whereas, normal male serum has 100- 300-fold less. This protein is a homolog of two human serum proteins: C reactive protein (CRP) and serum amyloid P (SAP) component. This family of proteins is called pentraxins because of their unusual structure - a pentamer of 5 non-covalently monomer subunits in a disk-like arrangement. Pentraxins are ancient proteins, have changed little during evolution and are found in most animals, even quite primitive ones as the horse shoe crab. These findings would suggest an important function for these proteins; however, a raison d'etre has not yet been described. FP shares many properties with CRP and SAP such as Ca++ dependent phosphorylcholine binding, compliment fixation, acute phase responsiveness and hepatic synthesis. FP is also a constituent of amyloid. Amyloid deposits in humans are most commonly found in brain of patients with Alzheimer's disease. However, in Syrian hamsters amyloidosis is unusual because it is very common and also is a sex- limited disease, preferentially expressed in females. Amyloid deposits in vital organs result in a shorter longevity of the female (versus male) Syrian hamster, an unusual phenomenon in mammals. Amyloidosis in Syrian hamsters can be directly related to serum FP levels in both male and female hamsters. Thus when FP synthesis (i.e., serum levels) is experimentally manipulated by hormonal means, expression of amyloidosis in both sexes is enhanced with high FP levels and is diminished with low levels. The Turkish hamster (Mesocricetus brandti) is a close relative of the Syrian hamster (Mesocricetus auratus) and also has a serum FP. The Turkish hamster's FP is antigenically identical to Syrian hamster FP and shares identical amino acid sequences. Although Turkish hamster FP is under similar sex-hormone control, the normal female serum levels are only 1/10 that found in Syrian hamster females. Commensurate with this low serum FP, amyloidosis was not found in aging normal Turkish hamsters. Amyloidosis was rare even after estrogen treatment, which markedly accelerates amyloidosis in Syrian hamsters. Turkish hamsters also differed from Syrian hamsters because prolonged estrogen treatment did not result in renal adenocarcinoma. On the other hand, normal old Turkish hamsters were found to have a high incidence of hepatocellular carcinoma (HCC). The appearance of HCC in Turkish hamsters was not enhanced by estrogen treatment as found in Armenian hamsters, and exogenous estrogen did not appear to have any acute hepatotoxic effect similar to that observed in Armenian hamsters.
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