Evans Maggie C, Hill Jennifer W, Anderson Greg M
Centre for Neuroendocrinology and Department of Anatomy, University of Otago, Dunedin, New Zealand.
Department of Physiology and Pharmacology, University of Toledo, Toledo, OH, USA.
J Neuroendocrinol. 2021 Feb 1;33(4):e12930. doi: 10.1111/jne.12930.
Infertility associated with insulin resistance is characterised by abnormal hormone secretion by the hypothalamus, pituitary gland and gonads. These endocrine tissues can maintain insulin sensitivity even when tissues such as the muscle and liver become insulin-resistant, resulting in excessive insulin stimulation as hyperinsulinaemia develops. Experiments conducted to determine the role of neuronal insulin signalling in fertility were unable to recapitulate early findings of hypogonadotrophic hypogonadism in mice lacking insulin receptors throughout the brain. Rather, it was eventually shown that astrocytes critically mediate the effects of insulin on puberty timing and adult reproductive function. However, specific roles for neurones and gonadotrophs have been revealed under conditions of hyperinsulinaemia and by ablation of insulin and leptin receptors. The collective picture is one of multiple insulin-responsive inputs to gonadotrophin releasing hormone neurones, with astrocytes being the most important player.
与胰岛素抵抗相关的不孕症的特征是下丘脑、垂体和性腺的激素分泌异常。即使肌肉和肝脏等组织出现胰岛素抵抗，这些内分泌组织仍能维持胰岛素敏感性，随着高胰岛素血症的发展，会导致胰岛素刺激过度。为确定神经元胰岛素信号在生育中的作用而进行的实验，无法重现全脑缺乏胰岛素受体的小鼠性腺功能减退症的早期研究结果。相反，最终发现星形胶质细胞在关键程度上介导了胰岛素对青春期时间和成年生殖功能的影响。然而，在高胰岛素血症条件下以及通过消除胰岛素和瘦素受体，已揭示了神经元和促性腺激素细胞的特定作用。总体情况是，促性腺激素释放激素神经元存在多种胰岛素反应性输入，其中星形胶质细胞是最重要的因素。
