Effect of gonadal steroids and gamma-aminobutyric acid on LH release and dopamine expression and activity in the zona incerta in rats

A dopaminergic system in the zona incerta stimulates LH release and may med iate the positive feedback effects of the gonadal steroids on LH release. i n this study the mechanisms by which steroids might increase dopamine activ ity in the zona incerta were investigated. Ln addition, experiments were co nducted to determine whether the inhibitory effects of gamma-aminobutyric a cid (GABA) on LH release in the zona incerta are due to suppression of dopa mine activity in this area or conversely whether the stimulatory effects of dopamine on LH release are due to suppression of a tonic inhibitory GABAer gic system. Ovariectomized rats were treated s.c. with oil, 5 mu g oestradi ol benzoate or 5 mu g oestradiol benzoate followed 48 h later by 0.5 mg pro gesterone, and killed 54 h after the oestradiol benzoate injection. At this time the LH concentrations were suppressed in the oestradiol benzoate grou p and increased in the group treated with oestradiol benzoate and progester one. The ratio of tyrosine hydroxylase:beta-actin mRNA in the zona incerta was significantly increased by the oestradiol benzoate treatment, but the a ddition of progesterone resulted in values similar to those in the control group. At the same time, the progesterone treatment increased tyrosine hydr oxylase activity in the zona incerta as indicated by an increase in L-dihyd roxyphenylalanine (L-DOPA) accumulation after 100 mg 3-hydroxybenzylhydrazi ne hydrochloric acid (NSD1015) kg(-1) and an increase in dopamine release a s indicated by a increase in dihydroxyphenylacetic acid (DOPAC) concentrati ons (one of the major metabolites of dopamine). Ovariectomized rats treated with oestradiol benzoate plus progesterone were also injected i.p. with 75 mg gamma-acetylenic GABA kg(-1) (a GABA transaminase inhibitor) to increas e GABA concentrations in the brain. This treatment had no effect on the rat io of tyrosine hydroxylase:P-actin mRNA but decreased L-DOPA accumulation a nd DOPAC concentrations in the zona incerta, indicating a post-translationa l inhibition of dopamine synthesis and release. Treatment of ovariectomized rats with oestradiol benzoate followed by 100 mg L-DOPA i.p. to increase d opamine concentrations in the whole brain had no effect on glutamic acid de carboxylase mRNA expression in the zona incerta, although it increased the glutamic acid decarboxylase:beta-actin mRNA ratio in other hypothalamic are as (that is, the medial preoptic area, ventromedial nucleus and arcuate nuc leus). in conclusion, the steroids act to increase dopamine activity in dif ferent ways: oestrogen increases tyrosine hydroxylase mRNA expression and p rogesterone acts after translation to increase tyrosine hydroxylase activit y and dopamine release (as indicated by increases in DOPAC concentrations). This latter effect may be due to progesterone removing a tonic GABAergic i nhibition from the dopaminergic system.