Most neurons in the hypothalamus make and secrete at least one peptide in addition to a conventional neurotransmitter and other intercellular messengers. Probably the most extensively characterized of these are the oxytocin and vasopressin neurones of the hypothalamus. Their evolution has been traced back to a single multisensory multifunctional cell type in Urbilateria, wormlike marine organisms that are the last common ancestor of vertebrates, flies, and worms. In Urbilateria, peptide-secreting cells probably responded to cues from the ancient marine environment. These earliest neurons combined properties that we have thought of as separate properties of endocrine cells and neurons. They used a diversity of signaling mechanisms, made both peptides and neurotransmitters, and were endowed with a wide range of specialized senses. They had not a single role to which they were committed, but multiple behavioral and physiological functions. The neurons of the hypothalamus have retained the multifunctionality of their distant ancestors, and their multitude of sensory abilities (1). Magnocellular oxytocin neurons regulate milk ejection, parturition, and sodium excretion by what they secrete into the blood (2). They also govern reproductive and appetitive behaviors, and these are governed reciprocally, not by the oxytocin that is released into the blood but by oxytocin released from dendrites. They are sensitive to multiple chemical cues from the internal environment—they have receptors for glucocorticoids and gonadal steroids, and for leptin, prolactin, and insulin, as well as for many of the peptides released from the brain itself. But to make sense of how single cell populations can simultaneously regulate diverse functions we have to separate hype from hope (3), sense from nonsense (4), and understand the mechanistic basis of independent regulation of secretion from different neuronal compartments (1, 5).

1. Leng, G (2018) The Heart of the Brain: the hypothalamus and its hormones. MIT Press
2. Leng G, Pineda Reyes R, Sabatier N, Ludwig M (2015) 60 YEARS OF NEUROENDOCRINOLOGY: The posterior pituitary: from Geoffrey Harris to our present understanding. J Endocrinol 226:T173-85.
3. Leng G, Ludwig M (2016) Intranasal oxytocin: myths and delusions. BiolPsychiatry 79:243-50.
4. Leng G, Sabatier N (2016) Measuring oxytocin and vasopressin: bioassays, immunoassays and random numbers. J Neuroendocrinol. (10).
5. Leng G, Sabatier N (2017) Oxytocin – The Sweet Hormone? Trends Endocrinol Metab. 28:365-376