Control of GnRH Secretion

Human reproduction and fertility are completely dependent upon neuroendocrine control of the hypothalamus-pituitary-gonadal (HPG) axis and its hierarchy of secreted hormones. The human reproductive system is controlled by the hypothalamus through the decapeptide gonadotropin-releasing hormone (GnRH), which displays a remarkable conservation over millions of years of evolution in the different species. The neurosecretion of GnRH depends on less than 4,000 GnRH-secreting neurons, which have an extracranial origin and finally migrate into the hypothalamic preoptic area. They secrete GnRH starting from the tenth week of gestation till the first 4–6 months of life, when GnRH secretion is “switched-off” until puberty. At puberty, the GnHR secretion is switched back “on” with a characteristic pulsatile manner that is maintained during adulthood. Regulation of GnRH-secreting neuron activity through the lifespan is not completely understood, but is clearly the result of a sophisticated network of stimulatory and inhibitory inputs, that include centrally different subgroups of neurons afferent to the GnRH-secreting neurons and peripherally the gonadal steroid feedback. The present chapter of the Textbook will focus on the ontogeny of the GnRH-secreting neurons and the mechanisms so far known to be implicated in regulating their neurosecretory activity.