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

Ongoing studies in our laboratory have demonstrated that systematically administered sex steroids 17ß-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 μM) on Purkinje cell responsiveness to microiontophoretically applied Glu. The inactive stereoisomer of E₂, 17α-E₂ (0.5 μM), estradiol benzoate (EB, 0.5 μM), and estrone (E₁, 0.5 μM) 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, 17α-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 17α-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.