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ToxSci Advance Access originally published online on September 29, 2004
Toxicological Sciences 2004 82(2):598-607; doi:10.1093/toxsci/kfh295
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Toxicological Sciences vol. 82 no. 2 © Society of Toxicology 2004; all rights reserved.

Endocrine Disruption in Adolescence: Immunologic, Hematologic, and Bone Effects in Monkeys

Mari S. Golub*,1, Casey E. Hogrefe{dagger}, Stacey L. Germann*,{dagger} and Christopher P. Jerome{ddagger}

* Department of Internal Medicine and {dagger} California National Primate Research Center, University of California, Davis, Davis, California 95616; and {ddagger} SkeleTech, Inc., Bothell, Washington, 98021

Received May 6, 2004; accepted September 22, 2004

Environmental contaminants with estrogenic properties have the potential to alter pubertal development. In addition to the reproductive system, other systems that mature under the influence of estrogen could be affected. This study examined the effect on immune, hematologic, and bone mass parameters of treatment with estrogenic agents (methoxychlor, MXC, 25 and 50 mg/kg/day; diethylstilbestrol, DES, 0.5 mg/kg/day) given in the peripubertal period to female rhesus monkeys. DES had striking effects on several parameters assessed measures CBC and clinical chemistry including hematocrit, hemoglobin, serum albumin, liver transaminases, and lipids. Circulating lymphocytes, particularly B cells, were depressed by DES, and a maturational shift in a memory T-cell population was altered. Bone mass and length, as measured after a 9-month recovery period, were significantly lower in the DES group and bone mass tended to be reduced in the femur of the MXC50 group relative to controls. In conclusion, the data indicate that DES had a clear effect on immunohematology and bone growth, while MXC influenced fewer parameters. Disruption in these systems during puberty could alter adolescent risk for anemia and infectious disease and subsequent adult risk for diseases such as osteoporosis, heart disease, and autoimmune disease.

Key Words: endocrine disruption; rhesus monkeys; methoxychlor; diethylstilbestrol; hematology; flow cytometry; bone mineral density; puberty; female.


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