Roger Guillemin, an internationally renowned physician and researcher, passed away on February 21, 2024 after celebrating his 100th birthday.
He was awarded the Nobel Prize in Physiology or Medicine in 1977 for fundamental discoveries that formed the basis of modern neuroendocrinology.
This French doctor-researcher, who later became Franco-American, was born in Dijon on January 11, 1924. He began his medical studies at the University of Burgundy and completed them in 1949 at the Faculty of Medicine in Lyon. He joined Hans Selye's team at the University of Montreal where he obtained a PhD in Physiology in Experimental Endocrinology in 1953. In this laboratory he met one of the founders of neuroendocrinology, Geoffrey Harris. This well-known researcher had accumulated very solid and complementary data – in vivo – showing the key role of the portal system in the relationship between the hypothalamus and the adenohypophysis. He had thus raised the hypothesis of the existence of hypothalamic neurotransmitters ("releasing factors") controlling the secretion of pituitary hormones. Following this meeting, Roger Guillemin had as his primary and permanent objective to identify the chemical structure of these putative hypothalamic neurohormones. He began the development of this project at Baylor College in Houston (USA) continued alternately with a stay at the Collège de France in Paris.
Given the limited sensitivity of the analytical methods of the time, he first had to accumulate hundreds of thousands of sheep hypothalami in order to have sufficient quantities of extracts to analyse. He achieved this feat first in France and then in Houston. At the same time, he surrounded himself with remarkable researchers with complementary expertise in technologies emerging at the time, such as chromatographic separations, mass spectrometry, primary cultures of pituitary cells and radioimmunoassays.
By combining these tools with virtuosity, in 1971 his group identified the first neurohormone, then called TRF, later known by the acronym TRH, which is involved in the pituitary release of TSH. One of the consequences of this discovery was the recruitment of Roger Guillemin by Jonas Salk. The researcher and his entire team moved to La Jolla in California to a Neuroendocrinology laboratory created especially for them at the Salk Institute. Once there, using similar approaches, they isolated and identified in 1972 the sequence of the decapeptide GnRH involved in the control of pituitary secretion of LH and FSH, then called LRF and then referred to by the acronym LHRH. Their results were published almost at the same time as those of Andrew Schally's group, which shared the Nobel Prize with Guillemin.
Using an analogous approach, this time looking for the hypothalamic factor involved in the stimulation of pituitary growth hormone (GH) release, the team, almost paradoxically, isolated an inhibitor of GH release in their extracts. Thus, the primary structure of this peptide, since called somatostatin, was published in 1973.
But Roger Guillemin was still looking for the factor that stimulates the release of GH. The isolation of what will become GHRH will in fact take a different route than the one taken to discover the other neuropeptides controlling pituitary hormone secretions. Indeed, its extraction and identification will be carried out directly from human tissue from a pancreatic tumor diagnosed by Dr. Geneviève Sassolas on a patient suffering from a particular and very rare form of acromegaly.
In addition to these achievements, of which we give only a glimpse here, it should also be remembered that Guillemin and his team have welcomed to the Salk-Institute a large number of international researchers, notably from Europe and France, contributing to the excellence of neuroendocrinology.
Thus, Prof. Roger Guillemin and his team have built modern transatlantic neuroendocrinology. Their major discoveries have not only been the basis for major advances in human physiology but have also allowed the synthesis of many molecules derived from these hypothalamic peptides. Their development has made it possible to make a dramatic leap in hormonal exploration and treatment of many endocrine diseases. More broadly, these therapeutic advances have made possible the modern care of thousands of patients around the world suffering from hormone-dependent diseases such as prostate cancer. This is not the least of the feats of this great Franco-American researcher born in Dijon.
Geneviève Sassolas, Jacques Young, Jérôme Bertherat, Huber Vaudry, Gérald Raverot.
on behalf of WES
04/03/2024