Endocrine disruption in adolescence: immunologic, hematologic, and bone effects in monkeys
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 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.
Discussion
Endocrine disruption in adolescence: immunologic, hematologic, and bone effects in monkeys, US National Library of Medicine National Institutes of Health, Toxicological sciences : an official journal of the Society of Toxicology, NCBI PubMed PMID: 15456917, 2004 Sep 29.
Full text, Oxford JournalsMedicine & HealthScience & Mathematics, Toxicological Sciences; Volume 82 Issue 2; Pp. 598-607, September 22, 2004.
Of potential public health significance is the different profile of the two agents, DES and MXC. While DES was much more effective in disrupting pubertal growth and menarche, MXC was more effective in disrupting behavior. In the current report, DES had greater effects on immunohematology, but DES and MXC similarly impacted bone mass. This suggests that health risk of exogenous estrogen exposure in adolescence is not readily generalizable across agents.
Regardless of the characterization of the effects, possible links to later health risks are of great interest. Although many of these estrogenic effects have already been documented in connection with estrogen therapies, corresponding health risks in human populations are not necessarily appreciated. For example, effects of estrogen on fibrinogen have been known for a number of decades, but consequences for fatal clotting incidents were not recognized until full-scale randomized trials of hormone replacement therapy were undertaken. In considering the toxicology of environmental estrogens, which have no therapeutic role, identification of long-term health risks are even more important, and nonhuman primate models can play an important role.
As regards endocrine disruption in adolescence, possible examples of long-term health risk are osteoporosis in the case of bone mineralization effects, autoimmunity in the case of shifts in lymphocyte populations, and cardiovascular disease in the case of cholesterol and triglyceride elevation. Red blood cell effects appeared to recover completely; however hematological effects could be considered a risk factor for anemia, a common problem in adolescent girls.
In summary, attention to the effects of endocrine disruption has focused on the reproductive system. However, long-term effects in a variety of systems relevant to future health could be altered when exogenous estrogens impinge on sensitive developmental periods. Some potential health impacts of estrogen disruption in adolescence include susceptibility to autoimmunity, heart disease, anemia, and osteoporosis.
More DES DiEthylStilbestrol Resources
- Other studies on DES and bones.
- Diethylstilbestrol DES studies by topics.