KNDy neurone activation prior to the LH surge of the ewe is disrupted by LPS

In the ewe, steroid hormones act on the hypothalamic arcuate nucleus (ARC) to initiate the GnRH/LH surge. Within the ARC, steroid signal transduction may be mediated by estrogen receptive dopamine-, β-endorphin- or neuropeptide Y (NPY)-expressing cells, as well as those co-localising kisspeptin, neurokinin B (NKB) and dynorphin (termed KNDy). We investigated the time during the follicular phase when these cells become activated (i.e., co-localise c-Fos) relative to the timing of the LH surge onset and may therefore be involved in the surge generating mechanism. Furthermore, we aimed to elucidate whether these activation patterns are altered after lipopolysaccharide (LPS) administration, which is known to inhibit the LH surge. Follicular phases of ewes were synchronised by progesterone withdrawal and blood samples were collected every 2 h. Hypothalamic tissue was retrieved at various times during the follicular phase with or without the administration of LPS (100 ng/kg). The percentage of activated dopamine cells decreased before the onset of sexual behaviour, whereas activation of β-endorphin decreased and NPY activation tended to increase during the LH surge. These patterns were not disturbed by LPS administration. Maximal co-expression of c-Fos in dynorphin immunoreactive neurons was observed earlier during the follicular phase, compared to kisspeptin and NKB, which were maximally activated during the surge. This indicates a distinct role for ARC dynorphin in the LH surge generation mechanism. Acute LPS decreased the percentage of activated dynorphin and kisspeptin immunoreactive cells. Thus, in the ovary-intact ewe, KNDy neurones are activated prior to the LH surge onset and this pattern is inhibited by the administration of LPS.