Pulsatile luteinizing hormone and follicle-stimulating hormone secretion and gonadotropin subunit mRNA levels in the ovariectomized GPR-4 transgenic rat.
Pulsatile luteinizing hormone and follicle-stimulating hormone secretion and gonadotropin subunit mRNA levels in the ovariectomized GPR-4 transgenic rat.
复制标题
去卵巢 GPR-4 转基因大鼠的脉动黄体生成素和卵泡刺激素分泌以及促性腺激素亚基 mRNA 水平。
DOI：
10.1159/000074881
复制
发表时间：
2003
影响因子：
4.1
通讯作者：
Weiner,RichardI
中科院分区：
文献类型：
--
作者：
ElMajdoubi,Mohammed;Paruthiyil,Sreenivasan;Weiner,RichardI
cAMP特异性磷酸二酯酶4D 1（PDE 4D 1）在GPR-4转基因大鼠中对促性腺激素释放激素（GnRH）神经元的遗传靶向导致去势雌性和雄性大鼠中黄体生成激素（LH）脉冲频率降低。在表达PDE 4D 1磷酸二酯酶的GT 1 GnRH细胞中观察到类似的内源性GnRH脉冲频率降低。我们在卵巢切除（OVX）GPR-4大鼠中扩展了这些发现，询问转基因表达对LH和促卵泡激素（FSH）的脉动分泌、血浆和垂体LH和FSH水平以及α-糖蛋白激素亚基（α-GSU）、LH-β和FSH-β亚基mRNA水平的影响。在OVX GPR-4大鼠中，与野生型同窝对照组相比，LH脉冲频率而非脉冲幅度降低了50%。测定相同样品的FSH，FSH脉冲频率和幅度不变。GPR-4大鼠的血浆和垂体前叶LH水平显著降低约45%，而血浆但非垂体前叶FSH水平显著降低25%。实时定量RT-PCR检测发现，GPR-4大鼠α-GSU、LH-β和FSH-β亚基的mRNA水平分别降低了41%、38%和28%。我们的结论是，在去势雌性GPR-4大鼠中，GnRH脉冲频率降低导致LH和FSH水平以及α和β亚基mRNA水平降低。
Genetic targeting of the cAMP-specific phosphodiesterase 4D1 (PDE4D1) to gonadotropin-releasing hormone (GnRH) neurons in the GPR-4 transgenic rat resulted in decreased luteinizing hormone (LH) pulse frequency in castrated female and male rats. A similar decrease in the intrinsic GnRH pulse frequency was observed in GT1 GnRH cells expressing the PDE4D1 phosphodiesterase. We have extended these findings in ovariectomized (OVX) GPR-4 rats by asking what effect transgene expression had on pulsatile LH and follicle-stimulating hormone (FSH) secretion, plasma and pituitary levels of LH and FSH, and levels of the α-glycoprotein hormone subunit (α-GSU), LH-β and FSH-β subunit mRNAs. In OVX GPR-4 rats the LH pulse frequency but not pulse amplitude was decreased by 50% compared to wild-type littermate controls. Assaying the same samples for FSH, the FSH pulse frequency and amplitude were unchanged. The plasma and anterior pituitary levels of LH in the GPR-4 rats were significantly decreased by approximately 45%, while the plasma but not anterior pituitary level of FSH was significantly decreased by 25%. As measured by real-time RT-PCR, the mRNA levels for the α-GSU in the GPR-4 rats were significantly decreased by 41%, the LH-β subunit by 38% and the FSH-β subunit by 28%. We conclude that in the castrated female GPR-4 rats the decreased GnRH pulse frequency results in decreased levels of LH and FSH and in the α- and β-subunit mRNA levels.