Quantitative three-dimensional reconstruction: feasibility for studies of sexually dimorphic hypothalamic development...

The adult rat brain develops through an interplay of neuronal proliferation with programmed cell death. Sensory stimulation, as well as growth factors and steroids, may alter the balance between these competing processes. "Endocrine disrupters" (EDs) may do the same by mimicry or modulation of endogenous hormones. The sexually dimorphic nucleus (SDN) of the medial preoptic hypothalamus contains a high concentration of estrogen receptors (ERs). The SDN develops to a final adult volume, which may be used as an indication of the hormonal conditions during perinatal development. Although male rats have been repeatedly observed to have a greater adult SDN volume than female rats, variability between the actual measurements reported (both within and between laboratories) have been rather large. Exposure of female rats to testosterone (or excessive estradiol, beyond the binding capacity of alpha-fetoprotein) has been shown to masculinize them through a P450 aromatase that converts testosterone to estrogen in the SDN. Exposure of males to estradiol may feminize them at low doses through interference with the synthesis of their endogenous testosterone, which normally acts on SDN ERs following aromatization. We have employed computer-assisted reconstruction methods in order to render the SDN within the surrounding hypothalamus in 3-D for computation of its volume. Ongoing studies are investigating whether exposure through the diet to estrogenic endocrine disruptors such as genistein, nonylphenol, and ethinyl estradiol might produce effects similar to those of estradiol itself on the adult SDN.