Locally applied estrogens potentiate glutamate-evoked excitation of cerebellar Purkinje cells.

Ongoing studies in our laboratory have demonstrated that systemically administered sex steroids 17 beta-estradiol (E2) and progesterone (P) alter cerebellar Purkinje cell responses to the amino acid neurotransmitter glutamate (Glu) in the urethane-anesthetized, ovariectomized adult rat. In the present study, we have examined the effects of locally pressure ejected E2 (0.5 microM) on Purkinje cell responsiveness to microiontophoretically applied Glu. The inactive stereoisomer of E2, 17 alpha-E2 (0.5 microM), estradiol benzoate (EB, 0.5 microM), and estrone (E1, 0.5 microM) were also tested (vehicle: 0.01% propylene glycol-saline, pH 7.4). Extracellular activity of single Purkinje neurons was recorded using multibarrel glass micropipets. Spontaneous firing rate and neuronal responses to microiontophoretic pulses (10 s every 40 s at 10-50 nA) of Glu were examined before, during and after continuous local pressure application of the steroids (1-5 psi, 10-15 min). Local E2 administration increased Glu response by 86% within 2-3 min after the onset of steroid application, with no recovery apparent by 30 min after termination of steroid administration. As such, local E2 application mimicked the effect of systemic injection of this steroid. The inactive estrogen isomer, 17 alpha-E2, failed to significantly enhance Glu responsiveness. Both EB and E1, however, significantly potentiated Glu responsiveness in a manner similar to locally applied E2. In addition, EB administration produced long-lasting increases in background discharge, unlike E2, and eventual recovery of Glu responses to control pre-steroid levels. In summary, this study provides a demonstration of local sex steroid actions on neuronal responsiveness in a model extrahypothalamic CNS area. These effects were specific, as the inactive 17 alpha-E2 isomer did not alter neuronal physiology. The results presented here suggest that the neuronal effects of systemic estrogen may be mediated by local actions of E2 or E1.