Evidence in favour of a direct input from the ventromedial nucleus to gonadotropin-releasing hormone neurones in the ewe: An anterograde tracing study

The mechanism by which oestrogen activates the gonadotropin releasing hormone (GnRH) neurones to induce the preovulatory luteinizing hormone (LH) surge is not understood. Previous work in the ewe has suggested that the primary site of action for oestradiol in stimulating the GnRH neurones was in the region of the ventromedial nucleus (VMN) within the mediobasal hypothalamus (MBH). In the present study, we used anterograde tracing techniques in the ewe to investigate whether direct neuronal projections may exist from neurones located in the region of the VMN to the GnRH neurones. Following the injection of biotinylated dextran amine into the VMN of four ewes, anterogradely labelled fibres were found located principally within the ipsilateral diagonal band of Broca (DBB), septum, preoptic and anterior hypothalamic areas, and periventricular, paraventricular, dorsomedial and arcuate nuclei of the MBH. Dual-labelling for GnRH revealed that fibres containing anterograde tracer were adjacent to the soma and/or dendrites of approximately 50% of all ipsilateral GnRH neurones located throughout the DBB and hypothalamus. Few anterogradely labelled fibres were detected within the median eminence. Although such studies cannot define the presence of direct synaptic connections between VMN neurones and the GnRH cells, these observations support further the hypothesis that oestrogen-sensitive VMN neurones represent a direct transsynaptic input to the GnRH cell bodies which are involved in the generation of the LH surge in the ewe.