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

Abstract

Ongoing studies in our laboratory have demonstrated that systematically administered sex steroids 17ß-estradiol (E 2) 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 E 2 (0.5 μM) on Purkinje cell responsiveness to microiontophoretically applied Glu. The inactive stereoisomer of E 2, 17α-E 2 (0.5 μM), estradiol benzoate (EB, 0.5 μM), and estrone (E 1, 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 E 2 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 E 2 application mimicked the effect of systemic injection of this steroid. The inactive estrogen isomer, 17α-E 2, failed to significantly enhance Glu responsiveness. Both EB and E 1, however, significantly potentiated Glu responsiveness in a manner similar to locally applied E 2. In addition, EB administration produced long-lasting increases in background discharge, unlike E 2, 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-E 2 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 E 2 or E 1.