History of hypothalamic research: “The spring of primitive existence”

The central brain region of interest for neuroendocrinology is the hypothalamus, a name coined by Wilhelm His in 1893. Neuroendocrinology is the discipline that studies hormone production by neurons, the sensitivity of neurons for hormones, as well as the dynamic, bidirectional interactions between neurons and endocrine glands. These interactions do not only occur through hormones, but are also partly accomplished by the autonomic nervous system that is regulated by the hypothalamus and that innervates the endocrine glands. A special characteristic of the hypothalamus is that it contains neuroendocrine neurons projecting either to the neurohypophysis or to the portal vessels of the anterior lobe of the pituitary in the median eminence, where they release their neuropeptides or other neuroactive compounds into the bloodstream, which subsequently act as neurohormones. In the 1970s it was found that vasopressin and oxytocin not only are released as hormones in the circulation but that their neurons project to other neurons within and outside the hypothalamus and function as neurotransmitters or neuromodulators that regulate central functions, including the autonomic innervation of all our body organs. Recently magnocellular oxytocin neurons were shown to send not only an axon to the neurohypophysis, but also axon collaterals of the same neuroendocrine neuron to a multitude of brain areas. In this way, the hypothalamus acts as a central integrator for endocrine, autonomic, and higher brain functions. The history of neuroendocrinology is described in this chapter from the descriptions in De humani corporis fabrica by Vesalius (1537) to the present, with a timeline of the scientists and their findings.