Increased hypothalamic GPR54 signaling: A potential mechanism for initiation of puberty in primates
Increased hypothalamic GPR54 signaling: A potential mechanism for initiation of puberty in primates
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DOI：
10.1073/pnas.0409822102
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发表时间：
2005-02-08
影响因子：
11.1
通讯作者：
Plant, TM
中科院分区：
文献类型：
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作者：
Shahab, M;Mastronardi, C;Plant, TM
为了进一步研究GPR 54信号在灵长类动物青春期开始中的作用，我们使用猴子来检查kisspeptin-10引起促性腺激素释放激素（GnRH）早熟释放的能力，我们描述了GPR 54和KiSS-1在青春期前后下丘脑中的表达。对无性腺幼年雄性猴植入侧脑室插管和颈静脉导管。在注射kisspeptin-10（112-121）之前，通过慢性脉动静脉输注合成GnRH，幼年垂体对内源性GnRH释放的反应性增强。脑室内（30 μ g或100 μ g）或静脉（100 μ g）推注kisspeptin-10引起了一个强大的GnRH放电，反映了促黄体激素分泌，这是取消了预处理与GnRH受体拮抗剂。从激动剂雄性动物的下丘脑中分离出RNA之前（青少年）和之后（青春期）的青春期复苏的脉冲式GnRH释放和青少年，青春期早期，和青春期中期卵巢完整的女性。KiSS-1 mRNA水平的实时PCR检测与青春期的男性和女性的猴子增加。在完整的雌性中，下丘脑中的GPR 54 mRNA水平从幼年期到青春期中期增加了约3倍，而在有性腺的雄性中则没有。杂交组织化学结果显示KiSS-1和GPR 54 mRNA在弓状核区域有强表达。这些研究结果是一致的假设，即GPR 54信号由其同源配体在灵长类动物下丘脑可能会被激活，在结束的青少年阶段的发展，并可能有助于青春期复苏的脉冲式GnRH释放，青春期的中央驱动器。
To further study the role of GPR54 signaling in the onset of primate puberty, we used the monkey to examine the ability of kisspeptin-10 to elicit the release of gonadotropin-releasing hormone (GnRH) precociously, and we describe the expression of GPR54 and KiSS-1 in the hypothalamus during the peripubertal period. Agonadal juvenile male monkeys were implanted with a lateral cerebroventricular cannula and a jugular vein catheter. The responsiveness of the juvenile pituitary to endogenous GnRH release was heightened with a chronic pulsatile i.v. infusion of synthetic GnRH before kisspeptin-10 (112-121) injection. Intracerebroventricular (30 mug or 100 mug) or i.v. (100 mug) bolus injections of kisspeptin-10 elicited a robust GnRH discharge, as reflected by luteinizing hormone secretion, which was abolished by pretreatment with a GnRH-receptor antagonist. RNA was isolated from the hypothalamus of agonadal males before (juvenile) and after (pubertal) the pubertal resurgence of pulsatile GnRH release and from juvenile, early pubertal, and midpubertal ovary-intact females. KiSS-1 mRNA levels detected by real-time PCR increased with puberty in both male and female monkeys. In intact females, but not in agonadal males, GPR54 mRNA levels in the hypothalamus increased approximate to3-fold from the juvenile to midpubertal stage. Hybridization histochemistry indicated robust KiSS-1 and GPR54 mRNA expression in the region of the arcuate nucleus. These findings are consistent with the hypothesis that GPR54 signaling by its cognate ligand in the primate hypothalamus may be activated at the end of the juvenile phase of development and may contribute to the pubertal resurgence of pulsatile GnRH release, the central drive for puberty.