Böttner M, Leonhardt S, Wuttke W, Jarry H
Department of Anatomy, University of Kiel, Kiel, Germany.
J Neuroendocrinol. 2007 Oct;19(10):779-87. doi: 10.1111/j.1365-2826.2007.01589.x.
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 ERalpha and ERbeta 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.
在雌性动物中，已有充分证据表明，随着年龄增长，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类的表达会发生变化。相比之下，对于这些与年龄相关的变化是否也发生在雄性动物中，我们却知之甚少。因此，我们设计了一项动物研究，对去势的年轻和中年雄性大鼠进行研究，以调查黄体生成素（LH）分泌模式的变化以及调节GnRH脉冲发生器活性的基因的mRNA表达变化。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脉冲相对较少且幅度减弱。此外，随着年龄增长，GnRH神经元所在的视前区和隔区的GnRH mRNA表达上调。对谷氨酸脱羧酶（GAD）的mRNA水平分析显示，中下丘脑（MBH）中GAD（65）和GAD（67）的mRNA表达增加，而视交叉上核中GAD（67）的mRNA水平降低。此外，我们观察到MBH中雌激素受体（ER）α的mRNA与年龄相关的增加，并且与年轻动物相比，中年大鼠垂体中ERα和ERβ的mRNA表达均上调。综上所述，我们的数据支持男性“雄激素缺乏症”的存在，即与女性的更年期一样，伴随着参与调节GnRH脉冲发生器功能的神经递质和激素受体表达的变化。
