Introduction

Sex-specific and temporally restricted, differential exposure of the developing male and female central nervous system (CNS) to gonadal steroid hormones such as the estrogens and the androgens has been implicated in the organization of neural circuits controlling a broad spectrum of sexually differentiated neuroendocrine, behavioral, and cognitive functions in the mammalian adult (1-4). Paradoxically, many actions of testosterone in the developing brain depend on its initial intraneuronal conversion, through aromatiza-tion, to estradiol. Metabolic conversion results in the subsequent binding of estradiol to high-affinity intranuclear estrogen receptors (ERs) (3), that are located within neurons of brain regions such as the hypothalamus, preoptic area, cerebral cortex, hippocampus and amygdala. These are all regions that are rich in aromatase activity, particularly during

From: Contemporary Endocrinology: Neurosteroids: A New Regulatory Function in the Nervous System Edited by: E.-E. Baulieu, P. Robel, and M. Schumacher © Humana Press Inc., Totowa, NJ

Fig. 1. (A) Neurite-promoting effects of estradiol in hypothalamic explant cultures, 19 d in vitro. Photomicrographs of right and left homologous coronal halves of a Holmes' silver-impregnated pair of explants from the preoptic area. Darkfield microscopy, x125. Control exposed only to estrogens endogenous to the 25% horse serum component of the nutrient medium. The silver-impregnated neurofibrils (bundles of neuron-specific, neurofilament proteins) course outward from the margin of the explant.

Fig. 1. (A) Neurite-promoting effects of estradiol in hypothalamic explant cultures, 19 d in vitro. Photomicrographs of right and left homologous coronal halves of a Holmes' silver-impregnated pair of explants from the preoptic area. Darkfield microscopy, x125. Control exposed only to estrogens endogenous to the 25% horse serum component of the nutrient medium. The silver-impregnated neurofibrils (bundles of neuron-specific, neurofilament proteins) course outward from the margin of the explant.

development (5). Increasing evidence, however, suggests that this widely held view of estrogen action in the developing brain is too restrictive and should be expanded beyond the strict confines of sexual differentiation. Thus estrogens, and estradiol in particular, have important consequences for neuronal development, survival, regeneration, plasticity, and even aging of the mammalian CNS.

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