School of Veterinary Science, University of Liverpool, Liverpool, UK.
Reproduction. 2017 Sep;154(3):281-292. doi: 10.1530/REP-17-0191. Epub 2017 Jun 19.
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.
在母羊中，甾体激素作用于下丘脑弓状核（ARC）以启动 GnRH/LH 激增。在 ARC 中，甾体信号转导可能由雌激素受体多巴胺、β-内啡肽或神经肽 Y（NPY）表达细胞以及那些共同表达 kisspeptin、神经激肽 B（NKB）和强啡肽（称为 KNDy）的细胞介导。我们研究了这些细胞在 LH 激增开始时相对激活的卵泡期时间（即 co-localise c-Fos），因此可能参与了激增产生机制。此外，我们旨在阐明这些激活模式是否在脂多糖（LPS）给药后发生改变，已知 LPS 抑制 LH 激增。通过孕酮撤药同步母羊的卵泡期，并每隔 2 小时采集一次血液样本。在卵泡期的不同时间，通过或不通过 LPS（100ng/kg）给药，采集下丘脑组织。在性行为开始之前，多巴胺细胞的激活百分比下降，而β-内啡肽的激活减少，NPY 的激活在 LH 激增期间趋于增加。这些模式没有因 LPS 给药而受到干扰。与在激增期间最大程度激活的 kisspeptin 和 NKB 相比，在卵泡期更早地观察到 dynorphin 免疫反应性神经元中 c-Fos 的最大共表达。这表明 ARC dynorphin 在 LH 激增产生机制中具有独特的作用。急性 LPS 降低了激活的 dynorphin 和 kisspeptin 免疫反应性细胞的百分比。因此，在卵巢完整的母羊中，KNDy 神经元在 LH 激增开始之前被激活，这种模式被 LPS 的给药所抑制。
