Changes of expression of genes related to the activity of the gonadotrophin-releasing hormone pulse generator in young versus middle-aged male rats
Changes of expression of genes related to the activity of the gonadotrophin-releasing hormone pulse generator in young versus middle-aged male rats
复制标题
DOI：
10.1111/j.1365-2826.2007.01589.x
复制
发表时间：
2007-10-01
影响因子：
3.2
通讯作者：
Jarry, H.
中科院分区：
文献类型：
--
作者：
Boettner, M.;Leonhardt, S.;Jarry, H.
在女性中，已经确定调节促性腺激素释放激素（GnRH）脉冲发生器活性的神经递质和肽的表达变化随着年龄的增长而改变。相比之下，人们对这些与年龄相关的变化是否也发生在男性身上知之甚少。因此，我们设计了一项动物研究，以兰科切除的年轻和中年雄性大鼠为研究对象，研究黄体生成素（LH）分泌谱的变化以及调节GnRH脉冲发生器活性的基因mRNA表达的变化。我们的研究结果表明，与年轻动物相比，中年大鼠的血清LH水平较低，LH脉冲相对较少，振幅减弱。此外，随着年龄的增长，GnRH mRNA的表达在视前区和GnRH神经元所在的鼻中隔上调。谷氨酸脱羧酶（GAD） mRNA水平分析显示，GAD（65）和GAD(67) mRNA在下丘脑中基底核（MBH）表达升高，视交叉上核GAD(67) mRNA表达降低。此外，我们观察到MBH中雌激素受体(ER) α mRNA的表达与年龄相关，与幼龄动物相比，中年大鼠垂体中ER α和ER β mRNA的表达均上调。综上所述，我们的数据支持男性“男性更年期”的存在，即像女性更年期一样，伴随着神经递质和激素受体表达的变化，这些变化参与调节GnRH脉冲发生器的功能。
In females, it is well established that changes in the expression of neurotransmitters and peptides regulating the activity of the gonadotrophin-releasing hormone (GnRH) pulse generator are altered during ageing. By contrast, little is known about whether those age-related changes also occur in males. Therefore, we designed an animal study with orchidectomised young and middle-aged male rats to investigate changes in luteinising hormone (LH) secretion profiles and changes in the mRNA expression of genes regulating the activity of the GnRH pulse generator. Our results demonstrate that middle-aged rats exhibit lower serum LH levels and relatively fewer LH pulses with attenuated amplitude compared to young animals. Furthermore, upon ageing, GnRH mRNA expression is up-regulated in the preoptic area and the septum where GnRH neurones reside. Analysis of mRNA levels of glutamate decarboxylase (GAD) enzymes revealed that GAD(65) and GAD(67) mRNA expression increased in the mediobasal hypothalamus (MBH) and that GAD(67) mRNA levels decreased in the suprachiasmatic nucleus. In addition, we observed an age-related increase of oestrogen receptor (ER)alpha mRNA in the MBH, and both ER alpha and ER beta mRNA expression was up-regulated in the pituitary of middle-aged rats compared to young animals. Taken together, our data support the existence of a male 'andropause' that is, like the menopause in females, accompanied by changes in neurotransmitter and hormone receptor expression that are involved in regulating the function of the GnRH pulse generator.