Estradiol Modulates the LH Release Response to N-Methyl-D-Aspartate in Adult Female Rats: Studies on Hypothalamic Luteinizing Hormone-Releasing Hormone and Neurotransmitter Release

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Abstract
We investigated the effect of ovariectomy (OVX) and subsequent estradiol benzoate (EB) treatment upon the N-methyl-D-aspartate (NMDA)-induced LH secretion in adult female rats. Furthermore, the release of LHRH, norepinephrine (NE), dopamine (DA), 5-hydroxyindoleacetic acid (5-HIAA) and γ-aminobutyric acid (GABA) from superfused hypothalamic fragments ex-planted from OVX and OVX-EB rats was determined. Two weeks after OVX, animals received EB (100 mg/kg) s.c, or oil vehicle (OVX-EB or OVX groups, respectively). Two days thereafter, at 09.00 h, NMDA (15 or 30 mg/ kg) was given as an i.v. bolus; blood samples were drawn before and 10 min after drug administration. In OVX rats, NMDA had no significant effect on LH levels, whereas it stimulated LH release in OVX-EB animals at both doses tested (315 and 362% from basal values, p < 0.001). For hypothalamic super-fusion studies OVX and OVX-EB animals were decapitated at 09.00 h, and the mediobasal hypothalami (MBH) dissected on ice. NMDA (10-4 M) was added to the superfusion medium for a 10 min period. Basal LHRH release (OVX: 1.41 ± 0.18; OVX-EB: 1.59 ± 0.28 pg/10 min/MBH) was significantly (p < 0.05) enhanced by NMDA (OVX: 2.97 ± 0.95; OVX-EB: 2.80 ± 0.61 pg/10 min/MBH). EB treatment had no significant effect on basal or NMDA-induced LHRH output. NMDA significantly (p < 0.05) decreased NE (OVX: 30.8 ± 6.7%; OVX-EB: 47.5 ± 9.7% from basal values), DA (OVX: 63.8 ± 10.7%; OVX-EB: 39.7 ± 14.6% from basal values), and 5-HIAA(OVX: 52.6 ± 7.7%; OVX-EB: 57.5 ± 9.7% from basal values) release, and increased GABA output (OVX: 155.6 ± 16.7%; OVX-EB: 183.1 ± 19.2% from basal values). The observation that OVX-EB rats show a massive LH release after NMDA, and that EB treatment does not alter NMDA-induced LHRH secretion, indicates that the predominant site of action of estradiol is exerted within the pituitary. The physiological implications of the NMDA-induced changes in neurotransmitter release remain to be studied.

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