Summary
The effects of intraventricular injections of the highly specific gamma-amino-butyric acid (GABA) agonist muscimol (5 nmol/animal) on blood LH and prolactin levels were measured in ovariectomized (ovx) and in ovx estrogen-progesterone (OEP) primed rats. While the drug stimulated pituitary prolactin release in both experimental groups, pituitary LH release was significantly inhibited in the ovx animals. Muscimol was without any effect on LH levels in ovx-OEP primed rats.
Bilateral implantation of tubes containing a muscimol-mannitol mixture into the medial preoptic/ anterior hypothalamic (MPO/AH) area abolished pulsatile LH release whereas blood prolactin values were elevated.
The intraventricular injection of GABA (8 μmol) also reduced LH and increased prolactin levels in the blood. Measurements of catecholamine turnover rates in the MPO/AH and in the mediobasal hypothalamus (MBH) yielded reduced preoptic but unchanged hypothalamic norepinephrine (NE) and stimulated hypothalamic dopamine (DA) turnover.
In view of the well known stimulatory involvement of the NE system in the mechanism of pulsatile LH release and the inhibitory effect of GABA and its agonist muscimol on pulsatile LH release, it is suggested that GABA inhibits NE release in the MPO/AH by the mechanism of presynaptic inhibition. The observation that muscimol is unable to suppress LH release in vox OEP-primed rats may indicate that those estrogen receptive neurons in the MPO/AH which mediate the negative feedback action of the steroid may use GABA as neurotransmitter and that they are the neurons which inhibit NE release. The inhibitory effect of locally implanted muscimol into the MPO/AH also supports this hypothesis. The facilitatory action of this implanted GABAergic drug on prolactin release points to the involvement of control mechanisms for the regulation of prolactin secretion which reside in the MPO/ AH. The stimulatory effect of intraventricularly injected GABA on hypothalamic DA turnover makes it likely that other than dopaminergic mechanisms are involved in mediating the stimulatory effect of GABA on prolactin release.
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Supported in part by the Deutsche Forschungsgemeinschaft (Grant Wu 60/5 and 6)
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Lamberts, R., Vijayan, E., Graf, M. et al. Involvement of preoptic-anterior hypothalamic GABA neurons in the regulation of pituitary LH and prolactin release. Exp Brain Res 52, 356–362 (1983). https://doi.org/10.1007/BF00238029
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DOI: https://doi.org/10.1007/BF00238029