Region- and peptide-specific regulation of the neurotrophins by estrogen

We have previously shown that estrogen increases the expression of brain-de rived neurotrophic factor (BDNF) mRNA in the olfactory bulb and cingulate c ortex. Here we report that estrogen regulation of BDNF protein and the stru cturally related peptides nerve growth factor (NGF) and neurotrophin (NT)-4 is region- and peptide-specific. The olfactory bulb and cingulate cortex a re both estrogen-sensitive targets and each receives a separate projection from neurons in the horizontal limb of the diagonal band of Broca (hlDBB). Furthermore, neurotrophins are retrogradely transported from the bulbar and cortical targets to the hlDBB. Four weeks of estrogen replacement to ovari ectomized animals increased BDNF expression in the olfactory bulb, but decr eased BDNF in the cingulate cortex. On the other hand, estrogen increased N T-4 expression in the cingulate cortex, but not in the olfactory bulb. NGF expression was not affected by estrogen in either region studied. In the hl DBB, estrogen increased BDNF but decreased NT-4, suggesting that estrogen d ifferentially affects retrograde accumulation of these peptides. While both estrogen receptor alpha and beta have been identified in the olfactory bul b and cingulate cortex, our results indicate that estrogen receptor alpha e xpression is relatively higher in the olfactory bulb as compared to the cor tex. Since the two estrogen receptors have been shown to stimulate differen t signaling pathways, we hypothesize that estrogen acting through specific receptors may differentially influence the extent and direction of neurotro phin expression. (C) 2000 Elsevier Science BN. All rights reserved.