Role of insulin in the neuroendocrine control of reproduction.

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.