Ciechanowska M, Apot M, Paruszewska E, Radawiec W, Przekop F
Department of Pharmacology and Toxicology, The General Karol Kaczkowski Military Institute of Hygiene and Epidemiology, Kozielska 4, 01-163 Warsaw, Poland.
The University of Warmia and Mazury, M. Oczapowskiego 2, 10-719 Olsztyn, Poland.
Reprod Fertil Dev. 2018 Mar;30(4):672-680. doi: 10.1071/RD16309.
This study aimed to explain how prolonged inhibition of central dopaminergic activity affects the cellular processes governing gonadotrophin-releasing hormone (GnRH) and LH secretion in anoestrous sheep. For this purpose, the study included two experimental approaches: first, we investigated the effect of infusion of sulpiride, a dopaminergic D2 receptor antagonist (D2R), on GnRH and GnRH receptor (GnRHR) biosynthesis in the hypothalamus and on GnRHR in the anterior pituitary using an immunoassay. This analysis was supplemented by analysis of plasma LH levels by radioimmunoassay. Second, we used real-time polymerase chain reaction to analyse the influence of sulpiride on the levels of kisspeptin (Kiss1) mRNA in the preoptic area and ventromedial hypothalamus including arcuate nucleus (VMH/ARC), and RFamide-related peptide-3 (RFRP-3) mRNA in the paraventricular nucleus (PVN) and dorsomedial hypothalamic nucleus. Sulpiride significantly increased plasma LH concentration and the levels of GnRH and GnRHR in the hypothalamic-pituitary unit. The abolition of dopaminergic activity resulted in a significant increase in transcript level of Kiss1 in VMH/ARC and a decrease of RFRP-3 in PVN. The study demonstrates that dopaminergic neurotransmission through D2R is involved in the regulatory pathways of GnRH and GnRHR biosynthesis in the hypothalamic-pituitary unit of anoestrous sheep, conceivably via mechanisms in which Kiss1 and RFRP-3 participate.
本研究旨在解释中枢多巴胺能活性的长期抑制如何影响控制处于乏情期绵羊促性腺激素释放激素（GnRH）和促黄体生成素（LH）分泌的细胞过程。为此，该研究包括两种实验方法：第一，我们使用免疫测定法研究了多巴胺能D2受体拮抗剂（D2R）舒必利的输注对下丘脑GnRH和GnRH受体（GnRHR）生物合成以及垂体前叶GnRHR的影响。通过放射免疫测定法分析血浆LH水平对这一分析进行了补充。第二，我们使用实时聚合酶链反应分析舒必利对视前区和包括弓状核在内的下丘脑腹内侧核（VMH/ARC）中 kisspeptin（Kiss1）mRNA水平，以及室旁核（PVN）和下丘脑背内侧核中RFamide相关肽-3（RFRP-3）mRNA水平的影响。舒必利显著提高了血浆LH浓度以及下丘脑-垂体单位中GnRH和GnRHR的水平。多巴胺能活性的消除导致VMH/ARC中Kiss1转录水平显著增加，PVN中RFRP-3水平降低。该研究表明，通过D2R的多巴胺能神经传递参与了乏情期绵羊下丘脑-垂体单位中GnRH和GnRHR生物合成的调节途径，可能是通过Kiss1和RFRP-3参与的机制。
