A century of GH research revisited: from linear models to network complexity

The history of GH started with the pioneer clinical and anatomical observations of Pierre Marie, who described the symptoms of acromegaly in 1886. Progressively, histochemical and histophysiological methods made it possible to characterize most cell types responsible for normal or pathological pituitary hormone secretion. Although the methods applied were indirect, and hormonal function assigned to each cell type could only be inferred from correlations, the quality of the corresponding studies was such that most of their results proved correct. In the second half of the XXth century, biochemical methods and bioassays led, between 1943 and 1956, to the production from pituitary extracts of highly purified fractions containing somatotropin activity. The subsequent demonstration that hypothalamo-hypophyseal interactions are of a neurohumoral nature permitted isolation of neuropeptides, a new class of neurotransmitters, many of which turned into major therapeutic agents. Subsequent purification of hundreds of neuropeptides, many with hypophysiotropic activity, and mapping of neurons producing them permitted to shift from relatively simple theories, postulating that stimulatory and inhibitory peptides are sufficient to account for the physiological control of pituitary secretion to more complex models. These permitted to understand how complex neuronal networks can produce a fine tuning of multiple combinations of neuropeptides and neurotransmitters, which interact with each other to adapt hormonal secretion to discrete physiological and pathological conditions.