促性腺激素释放激素拟似剂对青春期大鼠生长轴与性腺轴相关基因表达的影响

目的 探讨促性腺激素释放激素拟似剂(GnRHa)对青春期大鼠生长轴与性腺轴的影响及其作用机制。方法 青春期大鼠应用GnRHa后，取其下丘脑、垂体、卵巢、下肢骺软骨等组织，应用荧光定量PCR(FQ-PCR)技术检测组织中相应激素的基因表达水平。结果 GnRHa可使下丘脑中促性腺激素释放激素(GnRH)和垂体中GnRH受体(GnRHR)基因表达水平下降，下丘脑中生长激素释放抑制激素(SRIH)基因表达水平增高，生长激素释放激素(GHRH)基因表达无变化；垂体中生长激素(GH)、卵巢中雌激素受体(ER)、下肢骺软骨中胰岛素样生长因子—1(IGF-1)等基因表达水平均下降。结论GnRHa除抑制垂体GnRHR产生受体降调节外，还可抑制下丘脑GnRH的基因表达，使性腺激素水平降低，从而减缓第二性征的成熟程度和速度；同时GnRHa通过促进下丘脑SRIH的基因表达，抑制垂体GH和下肢骺软骨IGF-1的基因表达。这可能是Gn—RHa延缓特发性真性性早熟患儿骨骺闭合的机理之一。

Gene expression related to growth axis and gonadal axis in puberty rats

Objective To elucidate the effect and effective mechanism of gonadotropin releasing hormone analog (GnRHa) on growth axis and gonadal axis in puberty rats. Methods After injecting GnRHa on puberty rats, hypothalamus, pituitary, ovary and epiphyseal cartilage of legs were taken, and related gene expression was detected by fluorescence quantitative PCR (FQ PCR). Results GnRHa could reduce the gene expression of gonadotropin releasing hormone (GnRH) in hypothalamus and its receptor (GnRHR) in pituitary, increase the gene expression of growth hormone releasing inhibiting hormone (SRIH),and not affect the gene expression of growth hormone releasing hormone (GHRH) in hypothalamus. And GnRHa could reduce the gene expression of growth hormone (GH) in pituitary, estrogen receptor (ER) in ovary and insulin like growth factors I (IGF 1) in epiphyseal cartilage of legs. Conclusion Besides restraining the gene expression of GnRHR in pituitary and leading to descent regulation of receptor, GnRHa can reduce the gene expression of GnRH in hypothalamus and down regulate gonadal hormone level. At last, GnRHa can reduce the maturity degree and pace of the second sexual characteristics. By means of increasing the gene expression of SRIH in hypothalamus, GnRHa can reduce the gene expression of GH in pituitary and IGF 1 in epiphyseal cartilage of legs. It could be one of the mechanisms of GnRHa reducing epiphyseal maturity for the patients with idiopathic central precocious puberty.