雌性性早熟大鼠下丘脑、垂体褪黑素受体表达的变化

Expression of melatonin receptor in the hypothalamus and pituitary of female rats with precocious puberty

目的:通过研究雌性性早熟大鼠血浆褪黑素(melatonin,MT)水平,下丘脑、垂体MT受体MT1、MT2表达,探讨MT及MT受体在性发育启动和性早熟中的作用。方法:正常26日龄雌性SD大鼠40只,随机分为性早熟组、性早熟干预组、生理盐水对照组,后者又分为青春前期组和青春期组。使用N-甲基-DL-天冬氨酸(NMA)建立雌性性早熟大鼠模型,促性腺激素释放激素(GnRH)类似物(曲谱瑞林)干预性早熟,通过酶联免疫法检测各组大鼠夜间血浆MT促黄体生成素(LH)水平,实时定量PCR法检测下丘脑、垂体GnRH、MT1、MT2 mRNA表达。结果:各组大鼠夜间血浆MT水平无明显差异,性早熟组下丘脑及垂体MT1mRNA表达水平均低于青春前期组,差异具有统计学意义,与正常发育的青春期组比较无明显差异。与性早熟组相比,性早熟干预组下丘脑、垂体MT1 mRNA表达均升高,差异有统计学意义。下丘脑、垂体MT2表达各组间无差异。结论:雌性性早熟大鼠下丘脑、垂体MT1表达减少,GnRH类似物可上调MT1的表达。MT受体在青春期发育中可能起抑制性作用,通过下丘脑、垂体的MT受体表达的减少,减弱对中枢的抑制作用,参与正常青春发育或性早熟过程。

Objective： To explore the effect of melatonin and melatonin receptors on the onset of the puberty by observing the plasma concentration of melatonin and melatonin receptors （MT1 ,MT2）of hypothalamus and pituitary in precocious puberty female rats. Methods：A total of 40 26-day-old female SD rats were divided into the precocious puberty group （A）, the treated group （B）and the control groups including the prepuberty group （C 1 ） and the normal puberty group （C2）. N-methyl-DL-aspartic acid （NMA）was used to establish precocious puberty female rat model. GnRH analog （Triptorelin） were used to treat precocious puberty. The nocturnal plasma melatonin and luteinizing hormone （LH） level were assayed by enzyme linked immunosorbent assay （ELISA）and the expressions of melatonin receptors （MT1 ,MT2） and GnRH mRNA were conducted in bypothalamus and pituitary by real time-PCR. Results：There was no significant difference in the plasma melatonin level in each group. The expression of MT1 mRNA of rat hypothalamus and pituitary in the group A was significantly lower than in the group B and C1 ,and similar with the group C2. Each group showed no significant differences in the expressions of MT2 of hypotbalamus and pituitary. Conclusion：The expressions of MT1 mRNA decreased in precocious puberty female rats. GnRH analog may upregulate the expression of MT1 mRNA in hypothalamus and pituitary. The inhibitory effects of melatonin may decline due to the decreased expression of melatonin receptors in the central nervous system by decrease the expression of melatonin receptor in the hypotbalamus. Melatonin and its receptors may participate in normal puberty or precocious puberty.