Oestrogen, progesterone and serotonin converge on GABAergic neurones in the monkey hypothalamus

There are dense populations of inhibitory GABA neurones in regions of the p rimate hypothalamus that have been implicated in the neuroendocrine control of prolactin and luteinizing hormone (LH) secretion. A subpopulation of GA BA neurones that express nuclear oestrogen and progestin receptors reside i n the arcuate and infundibular nuclei. We questioned whether oestrogen or p rogesterone regulate the expression of GAD67, the rate limiting enzyme in G ABA synthesis, in these regions. Female monkeys were spayed and treated wit h placebo, oestrogen, progesterone or oestrogen plus progesterone for 28 da ys and GAD67 mRNA was examined with single in situ hybridization. In the ar cuate nucleus, there was no change in GAD67 mRNA expression with hormone tr eatment. However, in the infundibular region, oestrogen alone and oestrogen plus progesterone significantly suppressed GAD67 mRNA expression compared to spayed controls. In addition, expression of serotonin (5-HT)(2c) recepto r mRNA overlaps markedly with the expression of GAD67 mRNA in the same regi on. We tested the hypothesis that GABA neurones express 5-HT2c receptors us ing double in situ hybridization. The highest concentrations of double-labe lled cells were detected in the medial preoptic region, the arcuate nucleus and the infundibular region. The suprachiasmatic and ventromedial nuclei c ontained predominantly 5-HT2c mRNA expressing cells. The nucleus of the dia gonal band of Broca and the globus pallidus contained predominantly GAD67 m RNA expressing cells. The bed nucleus or the stria terminalis, the paravent ricular and dorsomedial nuclei contained different ratios of single-labelle d cells. Together these data suggest (i) that oestrogen decreases expressio n of GAD67 mRNA in the infundibular region which could lead to decreased GA BA synthesis, but addition of progesterone had no further effect and (ii) t hat GABA neurones in the same region also express mRNA for the stimulatory 5-HT2c receptor which could promote GABA release during serotonin input.