Structure and function in the conceptual development of mammalian neuroendocrinology between 1920 and 1965

With the growing realization in the 1930s that the brain played a crucial role in regulating the secretions of the pituitary gland, neuroendocrinology as we now know it developed from two rather separate directions. One approach relied heavily on morphological techniques to define neurosecretion; a novel, but for many years flawed model that was originally developed to explain the presence of gland-like cells in the diencephalon. During its first 20 years neurosecretion, as a concept, made no significant contribution to our understanding of how the pituitary was controlled. Then, following the identification by Sanford Palay and Wolfgang Bargmann of a continuous neurosecretory pathway from the hypothalamus to the neural lobe, neurosecretion became incorporated into a more broadly based concept of pituitary function, particularly regarding the neural lobe. The second approach integrated structural and functional methods to investigate neural regulation of the pituitary. This work eventually explained how the pituitary was controlled by the brain. It led directly to our understanding of the control of vasopressin and oxytocin release by neuroendocrine terminals in the neural lobe, the neurohumoral control of the pars distalis, and eventually to a detailed description of the neural networks that control pituitary function. As increasingly sophisticated morphological, neurophysiological, and eventually molecular biological techniques were applied to the problem, the original notion of the diencephalic gland and neurosecretion became unsustainable. The gland-nerve cells of the 1930s became the neurosecretory cells of the 1940s and 1950s, and then finally neuroendocrine neurons in the 1960s. From then on neuroendocrinology developed into the more unified discipline we know today. The chronology of these two approaches will be examined here using examples from research that occurred approximately between 1920 and 1965. The goal is not to give a comprehensive history of pituitary function or neuroendocrinology. Instead, the focus will be to compare the rationales and effectiveness of two contrasting experimental approaches: predominantly structural analyses as opposed to more integrated approaches.