Kalra P S, Bonavera J J, Kalra S P
Department of Physiology, University of Florida College of Medicine, Gainesville 32610, USA.
Regul Pept. 1995 Oct 20;59(2):215-20. doi: 10.1016/0167-0115(95)00093-q.
Compelling evidence shows that the episodic and cyclic secretion of hypothalamic luteinizing hormone releasing hormone (LHRH), the primary stimulator of pituitary LH release, is subject to regulation by neuropeptide Y (NPY). We have reported earlier that sequential treatment of ovariectomized (ovx) rats with estrogen and progesterone to stimulate a preovulatory-type LH surge elevated the levels of both NPY and preproNPY mRNA levels in the hypothalamus concomitant with dynamic changes in LHRH activity. The present study was designed to determine whether these elevations in NPY content and gene expression represent new synthesis of NPY that is crucial to elicit LHRH discharge. Ovx, steroid-primed rats received intracerebroventricular injections of an unmodified 20-mer oligodeoxynucleotide (oligo) complementary to the NPY mRNA sequence. Control rats were injected similarly with either saline or the sense or missense oligos. Results showed that control rats displayed a characteristic surge-type elevation in plasma LH levels that was not affected by the administration of missense or sense oligos. However, in rats injected with the antisense oligo, the steroid-induced LH surge was completely blocked. In an additional experiment, NPY peptide levels were measured in microdissected hypothalamic sites following the injection of antisense or missense oligos. NPY antisense oligo administration blocked the significant increases in NPY levels in the median eminence-arcuate area, the medial preoptic area and lateral preoptic area seen in control rats. These results suggest that sequential ovarian steroid treatment augments NPY synthesis in the hypothalamus and this newly synthesized NPY is critical for induction of the LHRH and LH surge.
有力证据表明，下丘脑促黄体生成素释放激素（LHRH）作为垂体促黄体生成素（LH）释放的主要刺激因子，其阵发性和周期性分泌受神经肽Y（NPY）调控。我们之前报道过，对去卵巢（ovx）大鼠先后给予雌激素和孕激素以刺激排卵前型LH峰，会使下丘脑NPY水平和前NPY原mRNA水平升高，同时LHRH活性发生动态变化。本研究旨在确定NPY含量和基因表达的这些升高是否代表对引发LHRH释放至关重要的NPY新合成。对ovx且经类固醇预处理的大鼠进行脑室内注射与NPY mRNA序列互补的未修饰20聚体寡脱氧核苷酸（oligo）。对照大鼠同样注射生理盐水或正义或错义寡核苷酸。结果显示，对照大鼠血浆LH水平呈现特征性的峰型升高，且不受错义或正义寡核苷酸给药的影响。然而，在注射反义寡核苷酸的大鼠中，类固醇诱导的LH峰被完全阻断。在另一项实验中，在注射反义或错义寡核苷酸后，对显微切割的下丘脑部位的NPY肽水平进行了测量。给予NPY反义寡核苷酸可阻断对照大鼠中在正中隆起 - 弓状核区域、内侧视前区和外侧视前区观察到的NPY水平的显著升高。这些结果表明，卵巢类固醇序贯治疗可增强下丘脑NPY的合成，且这种新合成的NPY对于诱导LHRH和LH峰至关重要。
