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ToxSci Advance Access published online on September 29, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh295
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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Received May 6, 2004
Accepted September 22, 2004

Reproductive and Developmental Toxicology

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

Mari S. Golub 1*, Casey E. Hogrefe 2, Stacey L. Germann 3, and Christopher P. Jerome 4

1 Dept Internal Medicine, University of California, Davis, CA 95616
2 California National Primate Research Center, University of California, Davis, CA 95616
3 Dept Internal Medicine, University of California, Davis, CA 95616; California National Primate Research Center, University of California, Davis, CA 95616
4 SkeleTech, Inc., Bothell, WA, 98021

* To whom correspondence should be addressed. E-mail: msgolub{at}ucdavis.edu.


  Abstract

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 in 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 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.

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