Neurosteroid Synthesis in Adult Female Rat Hippocampus, Including Androgens and Allopregnanolone

Abstract

Female rat hippocampus synthesizes significant amount of estrogens, including progesterone (PROG), estrone and estradiol (E2). Hippocampal level of PROG and E2 are considerably higher than those in plasma. Female hippocampal estrogens play a significant role in the fluctuation of dendritic spine density across the estrous cycle. Here we extend the study to the investigation of female androgens, including testosterone (T) and Dihydrotestosterone (DHT), in the female rat hippocampus, since female androgens had been largely unknown. By combination of mass-spectrometric analysis with HPLC-purification and picolinoyl-derivatization of sex steroids, we determined the accurate concentration of T and DHT in the hippocampus. The levels of T and DHT in female hippocampus at Proestrus were approximately 1.1 nM and 0.6 nM, respectively, suggesting a significant synthesis of T and DHT. The level of plasma T was approx. 0.1 nM, implying almost no contribution of plasma T to hippocampal T. The concentration of hippocampal DHT had a good correlation with that of hippocampal T, suggesting a significant activity of 5α-reductase (DHT synthase) in the female. Allopregnanolone level was also determined as a useful indicator of 5α-reductase activity. Interestingly mRNA expression level of 5α-reductase and androgen receptor (AR) was not significantly different between the different estrous cycle stages, or between female and male. Nevertheless, sex difference existed with respect to the levels of T, DHT and Allo in hippocampus. Although physiological significance of female hippocampal androgens waits further investigations, the female hippocampus produces T or DHT which may be useful to suppress anxiety, for example.