ORIGINAL ARTICLE: Oestrogen Synthesis in the Hippocampus: Role in Axon Outgrowth

• Published in: Journal of neuroendocrinology Vol. 18; no. 11; pp. 847 - 856
• Main Authors: von Schassen, C, Fester, L, Prange-Kiel, J, Lohse, C, Huber, C, Boettner, M, Rune, G M
• Format: Journal Article
• Language: English
• Published: 01.11.2006
• ISSN: 0953-8194; 1365-2826
• DOI: 10.1111/j.1365-2826.2006.01484.x

Ovarian oestrogens have been postulated to be neuroprotective. It has also been shown that considerable amounts of oestrogens are synthesised in hippocampal neurones. In the present study, we focused on a potential role of hippocampus-derived oestradiol compared to gonad-derived oestradiol on axon outgrowth of hippocampal neurones. To address the role of hippocampus-derived oestradiol, we inhibited oestrogen synthesis by treatment of neonatal hippocampal cell cultures with letrozole, a specific aromatase inhibitor. As an alternative, we used siRNA against steroidogenic acute regulatory protein (StAR). Axon outgrowth and GAP-43 expression were significantly down-regulated in response to letrozole and in siRNA-StAR transfected cells. The effects after inhibition of oestrogen synthesis in response to letrozole and in siRNA-StAR transfected cells were reversed by oestrogen supplementation. No difference was found between ovariectomised animals, cycling animals at pro-oestrus and ovariectomised and subsequently oestradiol-treated animals. However, high pharmacological doses of oestradiol promoted axon outgrowth, which was possible to abolish by the oestrogen receptor antagonist ICI 182,780. Our results show that oestradiol-induced neurite outgrowth is very likely mediated by genomic oestrogen receptors and requires higher doses of oestradiol than physiological serum concentrations derived from the gonads.