PROLACTIN-INDUCED AND TESTOSTERONE-INDUCED INHIBITION OF LH-SECRETIONAFTER ORCHIECTOMY - ROLE OF PREOPTIC AND TUBEROINFUNDIBULAR GAMMA-AMINOBUTYRIC ACIDERGIC NEURONS

The inhibitory amino acid neurotransmitter gamma-amino-butyric acid (G ABA) may play an important role in the regulation of LH-releasing horm one secretion. The present study examined the effect of prolactin on G ABAergic neuronal activity in microdissected brain regions of the orch idectomized rat, to determine whether inhibition of LH secretion after castration by acute hyperprolactinaemia was associated with prolactin -induced changes in GABAergic neuronal activity. The effects of prolac tin were contrasted with the effects of testosterone on hypothalamic G ABAergic neurones after orchidectomy. GABA concentrations were measure d by high pressure liquid chromatography in eight microdissected brain regions in untreated rats and 60 min after inhibition of the GABA cat abolic enzyme GABA transaminase by injection of amino-oxyacetic acid ( AOAA). The rate of GABA accumulation in microdissected brain regions f ollowing injection of AOAA was taken as an index of GABAergic neuronal activity. Rats were divided into seven experimental groups: intact co ntrols, 2 days after castration, 2 days after castration with prolacti n treatment (2.5 mg ovine prolactin injected s.c. every 12 h, starting at the time of castration), 2 days after castration with testosterone replacement (30 mm silicone elastomer implant containing crystalline testosterone), 6 days after castration, 6 days after castration with p rolactin treatment, and 6 days after castration with testosterone repl acement. Both 2 and 6 days alter castration, plasma LH was markedly el evated above levels in intact rats, and AOAA-induced GABA accumulation was significantly decreased in the diagonal band of Broca at the leve l of the organum vasculosum of the lamina terminalis, in the medial pr eoptic nucleus and in the median eminence. Hyperprolactinaemia signifi cantly reduced LH levels 2 days but not 6 days after castration. GABAe rgic neuronal activity, however, was not significantly affected by pro lactin at either time. Testosterone replacement blocked the postcastra tion elevation in plasma LH and prevented the castration-induced suppr ession of GABAergic neuronal activity both 2 and 6 days after castrati on. There were no castration- or hormone-induced changes in GABAergic neurones observed in the medial or lateral septum, caudate nucleus, ci ngulate cortex or arcuate nucleus. These results demonstrate that the activity of GABAergic neurones terminating in the rostral hypothalamus and the median eminence is positively regulated by testosterone, and that these steroid-sensitive GABAergic neurones may be important in th e negative-feedback control of LH secretion. inhibition of LH secretio n by hyperprolactinaemia, however, may not be mediated by changes in G ABAergic neuronal activity.