Department of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH, 43614, USA; Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH, 43614, USA.
Department of Physiology and Pharmacology, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH, 43614, USA; Center for Diabetes and Endocrine Research, College of Medicine and Life Sciences, The University of Toledo, Toledo, OH, 43614, USA.
Mol Cell Endocrinol. 2020 Dec 1;518:110996. doi: 10.1016/j.mce.2020.110996. Epub 2020 Aug 26.
The hypothalamic-pituitary-gonadal axis is controlled by gonadotropin-releasing hormone (GnRH) released by the hypothalamus. Disruption of this system leads to impaired reproductive maturation and function, a condition known as hypogonadotropic hypogonadism (HH). Most studies to date have focused on genetic causes of HH that impact neuronal development and function. However, variants may also impact the functioning of non-neuronal cells known as glia. Glial cells make up 50% of brain cells of humans, primates, and rodents. They include radial glial cells, microglia, astrocytes, tanycytes, oligodendrocytes, and oligodendrocyte precursor cells. Many of these cells influence the hypothalamic neuroendocrine system controlling fertility. Indeed, glia regulate GnRH neuronal activity and secretion, acting both at their cell bodies and their nerve endings. Recent work has also made clear that these interactions are an essential aspect of how the HPG axis integrates endocrine, metabolic, and environmental signals to control fertility. Recognition of the clinical importance of interactions between glia and the GnRH network may pave the way for the development of new treatment strategies for dysfunctions of puberty and adult fertility.
下丘脑-垂体-性腺轴受下丘脑释放的促性腺激素释放激素 (GnRH) 控制。该系统的破坏会导致生殖成熟和功能受损，这种情况被称为促性腺激素低下性性腺功能减退症 (HH)。迄今为止，大多数研究都集中在影响神经元发育和功能的 HH 的遗传原因上。然而，变体也可能影响称为神经胶质的非神经元细胞的功能。神经胶质细胞构成人类、灵长类动物和啮齿动物脑细胞的 50%。它们包括放射状胶质细胞、小胶质细胞、星形胶质细胞、室管膜细胞、少突胶质细胞和少突胶质细胞前体细胞。这些细胞中的许多都影响着控制生育能力的下丘脑神经内分泌系统。事实上，神经胶质细胞调节 GnRH 神经元的活动和分泌，在细胞体和神经末梢都起作用。最近的工作还清楚地表明，这些相互作用是 HPG 轴如何整合内分泌、代谢和环境信号来控制生育能力的一个重要方面。认识到神经胶质细胞与 GnRH 网络之间相互作用的临床重要性，可能为青春期和成年生育力功能障碍的新治疗策略的发展铺平道路。
