Estradiol Attenuates a,-Adrenoceptor-Mediated Inhibition of Hypothalamic Norepinephrine Release

These studies tested the hypothesis that estradiol facilitates norepinephrine (NE) neurotransmission by modulating LY*adrenoceptor-mediated inhibition of NE release. KCI-induced overflow of 3H from superfused slices preloaded with 3H-NE was Ca2+ dependent. Hypothalamic slices from estradiol-treated rats exposed to a single KCI pulse (Sl ) had modestly (20%) but significantly elevated NE release when compared to slices from ovariectomized (OVX) rats. Blockade of a,-adrenoceptors by pretreatment with the imidazoline antagonists idazoxan (IDA) and RX821002 (RX) markedly facilitated NE release during Sl in hypothalamic slices from OVX rats; this facilitation was attenuated or absent in slices from estradiol-treated rats. In additional studies slices were stimulated twice, 24 min apart (Sl and S2), for 3 min with 20 mM KCI. In the absence of drug, the amount of 3HNE released during S2 was always less than the amount released during Sl (i.e., S2:Sl = 0.6), regardless of whether slices were from OVX or estradiol-treated females. When 10 PM IDA was applied after Sl and 15 min prior to S2, the S2: Sl ratio increased to 1.8 f 0.1 in hypothalamic slices from OVX animals. In contrast, the S2:Sl ratio rose only to 1 .I -t 0.2 in slices from estradiol-treated animals. RX applied before S2 markedly increased the S2:Sl ratio in both hypothalamic and preoptic area slices from OVX rats but failed to increase the S2:Sl ratio in slices from estradiol-treated rats. Interestingly, the modest effects of alkaloid a,-antagonists such as yohimbine and rauwolscine on NE release in hypothalamic and preoptic area slices were not modified by estradiol. These results suggest that a,-adrenergic inhibition of NE release is highly active in the hypothalamus of OVX female rats and that this inhibition is attenuated by estradiol. Furthermore, estradiol may specifically regulate the a,,-adrenoceptor subtype. [