Haisenleder D J, Yasin M, Dalkin A C, Gilrain J, Marshall J C
Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Endocrinology. 1996 Dec;137(12):5719-22. doi: 10.1210/endo.137.12.8940405.
Recent studies have demonstrated that the nuclear receptor, steroidogenic factor 1 (SF-1) plays a role in the regulation of pituitary gonadotropin gene expression. As GnRH is critical to stimulating LH and FSH gene expression, the present study was conducted to determine whether GnRH also regulates pituitary SF-1 mRNA. Pituitary SF-1 mRNA levels were measured in individual animals by RNase protection assay. In the first study, adult male and female rats were gonadectomized (GDX) for 7 days and some received testosterone (T) to prevent the post-GDX rise in GnRH, and compared to intact animals. Pituitary SF-1 mRNA levels increased significantly (3 fold in males, 2 fold in females; p < 0.05 vs intacts) after gonadectomy, which was blocked by exogenous T. Similar changes were observed in serum LH. To directly test whether GnRH stimulates SF-1 mRNA, we used a GnRH-deficient rat model (phenoxybenzamine-treated, ovariectomized females) and administered GnRH pulses for 6h (5ng at 30 min intervals; saline pulses to controls). Pulsatile GnRH stimulated a 51-64% increase in SF-1 mRNA levels (p < 0.05 vs controls). These results show that GnRH stimulates SF-1 gene expression, which may be a critical component in GnRH stimulation of gonadotropin subunit transcription.
最近的研究表明,核受体类固醇生成因子1(SF-1)在垂体促性腺激素基因表达的调节中发挥作用。由于促性腺激素释放激素(GnRH)对刺激促黄体生成素(LH)和促卵泡生成素(FSH)基因表达至关重要,因此进行本研究以确定GnRH是否也调节垂体SF-1 mRNA。通过核糖核酸酶保护试验测量个体动物的垂体SF-1 mRNA水平。在第一项研究中,成年雄性和雌性大鼠去势7天,一些大鼠接受睾酮(T)以防止去势后GnRH升高,并与完整动物进行比较。去势后垂体SF-1 mRNA水平显著升高(雄性升高3倍,雌性升高2倍;与完整动物相比,p<0.05),外源性T可阻断这种升高。在血清LH中也观察到类似变化。为了直接测试GnRH是否刺激SF-1 mRNA,我们使用了GnRH缺陷大鼠模型(经苯氧苄胺处理的去卵巢雌性大鼠),并给予GnRH脉冲6小时(每隔30分钟5 ng;对照组给予生理盐水脉冲)。脉冲式GnRH刺激SF-1 mRNA水平升高51%-64%(与对照组相比,p<0.05)。这些结果表明,GnRH刺激SF-1基因表达,这可能是GnRH刺激促性腺激素亚基转录的关键组成部分。