Brann Darrell W, Mahesh Virendra B
Institute of Medicine and Genetics, Institute of Neuroscience, Developmental Neurobiology Program, Department of Neurology, Medical College of Georgia, Augusta, GA 30912-3000, USA.
Steroids. 2005 Apr;70(4):273-83. doi: 10.1016/j.steroids.2004.12.008.
It is well known that the reproductive system is one of the first biological systems to show age-related decline. While depletion of ovarian follicles clearly relates to the end of reproductive function in females, evidence is accumulating that a hypothalamic defect is critical in the transition from cyclicity to acyclicity. This minireview attempts to present a concise review on aging of the female reproductive neuroendocrine axis and provide thought-provoking analysis and insights into potential future directions for this field. Evidence will be reviewed, which shows that a defect in pulsatile and surge gonadotropin hormone-releasing hormone (GnRH) secretion exists in normal cycling middle-aged female rats, which is thought to explain the significantly attenuated pulsatile and surge luteinizing hormone (LH) secretion at middle-age. Evidence is also presented, which supports the age-related defect in GnRH secretion as being due to a reduced activation of GnRH neurons. Along these lines, stimulation of GnRH secretion by the major excitatory transmitter glutamate is shown to be significantly attenuated in middle-aged proestrous rats. Corresponding age-related defects in other major excitatory regulatory factors, such as catecholamines, neuropeptide Y, and astrocytes, have also been demonstrated. Age-related changes in hypothalamic concentrations of neurotransmitter receptors, steroid receptors, and circulating steroid hormone levels are also reviewed, and discussion is presented on the complex interrelationships of the hypothalamus-pituitary-ovarian (HPO) axis during aging, with attention to how a defect in one level of the axis can induce defects in other levels, and thereby potentiate the dysfunction of the entire HPO axis.
众所周知，生殖系统是最早出现与年龄相关衰退的生物系统之一。虽然卵巢卵泡的耗竭显然与女性生殖功能的终止有关，但越来越多的证据表明，下丘脑缺陷在从周期性到无周期性的转变中起着关键作用。本综述试图对女性生殖神经内分泌轴的老化进行简要回顾，并对该领域未来可能的方向提供发人深省的分析和见解。将回顾相关证据，这些证据表明正常处于发情周期的中年雌性大鼠存在促性腺激素释放激素（GnRH）脉冲式分泌和高峰式分泌缺陷，这被认为可以解释中年时黄体生成素（LH）脉冲式分泌和高峰式分泌显著减弱的原因。还将展示支持GnRH分泌存在与年龄相关缺陷是由于GnRH神经元激活减少的证据。按照这些思路，在中年动情前期大鼠中，主要兴奋性递质谷氨酸对GnRH分泌的刺激作用显著减弱。其他主要兴奋性调节因子，如儿茶酚胺、神经肽Y和星形胶质细胞，也有相应的与年龄相关的缺陷。还将回顾下丘脑神经递质受体、类固醇受体浓度以及循环类固醇激素水平与年龄相关的变化，并讨论衰老过程中下丘脑-垂体-卵巢（HPO）轴的复杂相互关系，关注轴的一个水平的缺陷如何诱导其他水平的缺陷，从而加剧整个HPO轴的功能障碍。
