Vadakkadath Meethal S, Atwood C S
Section of Geriatrics and Gerontology, Department of Medicine, University of Wisconsin, Veterans Administration Hospital, Madison, Wisconsin 53705, USA.
Cell Mol Life Sci. 2005 Feb;62(3):257-70. doi: 10.1007/s00018-004-4381-3.
Receptors for hormones of the hypothalamic-pituitary-gonadal (HPG) axis that regulate reproductive function are expressed throughout the brain, and in particular the limbic system. The most studied of these hormones, the sex steroids, contain receptors throughout the brain, and numerous estrogenic, progestrogenic and androgenic effects have been reported in the brain related to development, maintenance and cognitive functions. Although less studied, receptors for gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and activins also are found throughout the limbic system on a number of cell types, and they too transduce signals from circulating hormones as demonstrated by their multiple effects on the growth, development, maintenance and function of the brain. This review highlights the point that because of the feedback loops within the HPG axis, it is difficult to ascribe structural and functional changes during development, adulthood and senescence to a single HPG hormone, since a change in the concentration of any hormone in the axis will modulate hormone concentrations and/or receptor expression patterns for all other members of the axis. The most studied of these situations is the change in serum and neuronal concentrations of HPG hormones associated with menopause/andropause. Dysregulation of the HPG axis at this time results in increases in the concentrations of serum GnRH, gonadotropins and activins, decreases in the serum concentrations of sex steroid and inhibin, and increases in GnRH and LH receptor expression. Such changes would result in significantly altered neuronal signaling, with the final result being that there is i.e. increased neuronal GnRH, LH and activin signaling, but decreased sex steroid signaling. Therefore, loss of cognitive function during senescence, typically ascribed to sex steroids, may also result from increased signaling via GnRH, LH or activin receptors. Future studies will be required to differentiate which hormones of the HPG axis regulate/maintain cognitive function. This introductory review highlights the importance of the identification of HPG hormone neuronal receptors and the potential of serum HPG hormones to transduce signals to regulate brain structure and function during development and adult life.
调节生殖功能的下丘脑 - 垂体 - 性腺（HPG）轴激素的受体在整个大脑中表达，尤其是在边缘系统。这些激素中研究最多的是性类固醇，其受体遍布大脑，并且在大脑中已报道了许多与发育、维持和认知功能相关的雌激素、孕激素和雄激素效应。虽然研究较少，但促性腺激素释放激素（GnRH）、黄体生成素（LH）和激活素的受体也存在于边缘系统的多种细胞类型中，并且它们同样能转导循环激素的信号，这已通过它们对大脑生长、发育、维持和功能的多种作用得到证实。本综述强调了这样一个观点，即由于HPG轴内存在反馈回路，很难将发育、成年期和衰老过程中的结构和功能变化归因于单一的HPG激素，因为轴内任何一种激素浓度的变化都会调节轴内所有其他成员的激素浓度和 / 或受体表达模式。这些情况中研究最多的是与绝经 / 男性更年期相关的HPG激素血清和神经元浓度变化。此时HPG轴的失调导致血清GnRH、促性腺激素和激活素浓度升高，性类固醇和抑制素血清浓度降低，以及GnRH和LH受体表达增加。这些变化将导致神经元信号显著改变，最终结果是神经元GnRH、LH和激活素信号增加，但性类固醇信号减少。因此，衰老过程中认知功能丧失通常归因于性类固醇，也可能是由于通过GnRH、LH或激活素受体的信号增加所致。未来需要进行研究以区分HPG轴的哪些激素调节 / 维持认知功能。这篇引言性综述强调了识别HPG激素神经元受体的重要性以及血清HPG激素在发育和成年期转导信号以调节脑结构和功能的潜力。
