The effects of hormones such as estrogen, testosterone, and their multiple active metabolites proceed by several distinct mechanisms. Testosterone is metabolized to the much more potent dihydrotestosterone (DHT) and then to estradiol. Binding of DHT and estradiol to specific receptors in the cell nucleus affects transcription of a broad variety of genes. Estrogen also promotes neurogenesis and synaptic growth directly or via stimulation of GABAergic neurons (McCarthy, Schwarz, Wright, & Dean, 2008). Early in development, GABA acts as an activating neurotransmitter and induces synaptogenesis. In addition to slower transcriptome-mediated effects, estrogen can act quickly through a membrane bound receptor and through second messenger systems (Balthazart & Ball, 2006; Milner et al., 2001). In addition to effects that are related to GABA transmission, the rate of conversion of testosterone to estradiol by aromatase changes in response to fluctuating glutamate levels. Modulation of local estrogen dosages by the rapid conversion of testosterone to estradiol allows effectiveness of estrogen as a neurotransmitter. Although both males and females have endogenous testosterone, which could serve as a substrate for aromatase, it is not known how the much lower endogenous levels of testosterone in females may affect this pathway.
