The Syrian hamster has an unusual serum protein under control of sex hormones. This protein is called female protein (FP) because of its special expression in females where serum levels are 100-200 fold greater than in normal males. FP is a homolog of two human proteins: C reactive protein (CRP) and serum amyloid P component (SAP). This family of proteins is called pentraxin and are found in most animals and birds. Pentraxins have evolved with little change in structure. These findings would imply an important function of pentraxins, however, a raison d'etre has not been described. 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 SAP). 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 in Syrian hamsters. The high serum levels of FP may be 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. Estrogen administered to male hamsters enhances expression of amyloidosis; however, only those estrogens which increase FP synthesis (such as diethylstilbestrol) will have this effect. The sex hormone control of FP synthesis in the Syrian hamster provides a unique opportunity to examine the role of this pentraxin in amyloidosis. FP synthesis is under different control mechanism in other hamsters. For example, in Armenian hamster, FP is down regulated by estrogen administration, and this turn off of FP synthesis may be related to the acute hepatic toxicity and chronic hepatocarcinogenesis induced by exogenous estrogens. A variety of plant foods contain estrogens (mycoestrogens and phytoestrogens), and these foods may be responsible for the known influence of diet on development of certain human diseases such as breast and prostate cancer. Because hamsters are so sensitive to the effects of estrogens, we have been feeding hamsters various estrogenic foods to determine if dietary estrogens can 1) alter hepatic synthesis of FP, 2) change expression of amyloidosis, 3) influence the estrogen initiation of kidney and liver tumors. Because of technical problems, these experimental results are preliminary but do indicate that flax consumption may alter expression of amyloidosis, and a soy bean diet may change hepatic FP synthesis and influence the hepatic response to exogenous estrogens.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI000262-12
Application #
3746492
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
12
Fiscal Year
1993
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code