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

There are dense populations of inhibitory GABA neurones in regions of the primate hypothalamus that have been implicated in the neuroendocrine control of prolactin and luteinizing hormone (LH) secretion. A subpopulation of GABA neurones that express nuclear oestrogen and progestin receptors reside in the arcuate and infundibular nuclei. We questioned whether oestrogen or progesterone regulate the expression of GAD67, the rate limiting enzyme in GABA synthesis, in these regions. Female monkeys were spayed and treated with placebo, oestrogen, progesterone or oestrogen plus progesterone for 28 days and GAD67 mRNA was examined with single in situ hybridization. In the arcuate nucleus, there was no change in GAD67 mRNA expression with hormone treatment. 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 receptor mRNA overlaps markedly with the expression of GAD67 mRNA in the same region. We tested the hypothesis that GABA neurones express 5-HT2C receptors using double in situ hybridization. The highest concentrations of double-labelled cells were detected in the medial preoptic region, the arcuate nucleus and the infundibular region. The suprachiasmatic and ventromedial nuclei contained predominantly 5-HT2C mRNA expressing cells. The nucleus of the diagonal band of Broca and the globus pallidus contained predominantly GAD67 mRNA expressing cells. The bed nucleus of the stria terminalis, the paraventricular and dorsomedial nuclei contained different ratios of single-labelled cells. Together these data suggest (i) that oestrogen decreases expression of GAD67 mRNA in the infundibular region which could lead to decreased GABA synthesis, but addition of progesterone had no further effect and (ii) that GABA neurones in the same region also express mRNA for the stimulatory 5-HT2C receptor which could promote GABA release during serotonin input.