Different Forms of Oestrogen Rapidly Upregulate Cell Proliferation in the Dentate Gyrus of Adult Female Rats

Oestrogens are known to exert significant structural and functional effects in the hippocampus of adult rodents. The dentate gyrus of the hippocampus retains the ability to produce neurones throughout adulthood and 17 beta-oestradiol has been shown to influence hippocampal neurogenesis in adult female rats. The effects of other oestrogens, such as oestrone and 17 alpha-oestradiol, on neurogenesis have not been investigated. The present study aimed to investigate the effects of 17 beta-oestradiol, oestradiol benzoate, oestrone, and 17 alpha-oestradiol on cell proliferation in ovariectomised adult female rats at two different time points. Young ovariectomised female rats were injected with one of the oestrogens at one of three doses. In Experiment 1, rats were exposed to the hormone for 4 h and, in Experiment 2, rats were exposed to the hormone for 30 min prior to 5-bromo-2-deoxyuridine injection to label proliferating cells and their progeny. We found that young ovariectomised females responded with increased cell proliferation to most oestrogens, except oestradiol benzoate, after 30 min of exposure. However, administration of oestrogens for a longer time interval was ineffective at increasing cell proliferation. After 30 min, 17 beta-oestradiol and oestrone increased cell proliferation at low (0.3 mu g) and high (10 mu g) doses, whereas 17 alpha-oestradiol increased cell proliferation at medium (1 mu g) and high doses. The results of the present study indicate that different oestrogens rapidly increase cell proliferation in a dose-dependent manner, possibly through a nonclassical, nongenomic mechanism. Future experiments should focus on further elucidating the specific pathways utilised by each oestrogen. These results have important therapeutic implications because it may be possible to use 17 alpha-oestradiol and lower doses of oestrogens in hormone replacement therapies.