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ToxSci Advance Access originally published online on September 29, 2004
Toxicological Sciences 2004 82(2):570-576; doi:10.1093/toxsci/kfh297
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Toxicological Sciences vol. 82 no. 2 © Society of Toxicology 2004; all rights reserved.

Increased Volume of the Calbindin D28k-Labeled Sexually Dimorphic Hypothalamus in Genistein and Nonylphenol-Treated Male Rats

A. C. Scallet*,1, R. L. Divine{dagger}, R. R. Newbold{ddagger} and K. B. Delclos§

* Division of Neurotoxicology National Center for Toxicological Research/FDA, Jefferson, Arkansas 72079; {dagger} Charles River Laboratories, Jefferson, Arkansas 72079; {ddagger} Environmental Toxicology Program, National Institute for Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709; and § Division of Biochemical Toxicology, National Center for Toxicological Research/FDA, Jefferson, Arkansas 72079

Received July 16, 2004; accepted September 7, 2004

The adult rat brain develops through an interplay of neuronal proliferation and programmed cell death. Steroid hormones and growth factors may alter the balance between these competing processes. "Endocrine disrupters" (EDs) may also alter brain development, by mimicry or modulation of endogenous hormone systems. Under control conditions, the sexually dimorphic nucleus (SDN) of the medial preoptic hypothalamus becomes larger in adult males than females, but its final volume may also reflect the hormonal conditions prevailing during development. Two EDs that have recently been studied in protocols involving lifespan exposures are the phytoestrogen genistein and the weakly estrogenic compound para-nonylphenol, which is used in the production of many surfactants and plastics. Experimental dietary exposure of adult female rats to genistein or p-nonylphenol began 28 days prior to their mating at concentrations of 5 ppm, 100 ppm, and 500 ppm for genistein or 25 ppm, 200 ppm, and 750 ppm for p-nonylphenol. Exposure of the offspring continued throughout gestation and lactation, as well as in their chow after weaning, until they were sacrificed at 140 days of age for immunohistochemical labeling of the calbindin D28k-labeled subdivision of the SDN: the CALB-SDN. Both genistein and nonylphenol were found to increase the volume of the CALB-SDN in male rats (p's < 0.01), but not in female rats.

Key Words: medial preoptic nucleus; hypothalamus; 3-D reconstruction; endocrine disrupters; estrogens; sex differences; calcium binding proteins.


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