“Hormones” of the Pineal Gland
MEDICAL research at the biochemical level necessitates thinking about disease on a wide basis. Incidental knowledge acquired in the study of one disease has often proved to be of great use in the understanding or treatment of another.
The serotonin story is a good example of this, the gradual unfolding of its theme having been undertaken by scientists whose primary interests included mental, cardiovascular, endocrine, dermatologic and neoplastic disease.1 Serotonin was first isolated from the blood by Rapport, Green, and Page at the Cleveland Clinic because they were interested in its effects on blood pressure. Later it was found to be present in brain and was thought to be a neurohormone. In fact, the hallucinogenic effects of lysergic acid diethylamide (LSD) were thought to be due to the serotonin antagonistic action of this compound.
It was then observed that the carcinoid syndrome was due to large quantities of serotonin produced by the neoplastic tissue, and as an aid to the diagnosis of the condition, Udenfriend, Titus, Weissbach, and Peterson2 identified the major urinary metabolite 5-hydroxyindoleacetic acid. Other metabolic pathways, however, were unknown.
Since we thought that the metabolism of serotonin might be related to mental and cardiovascular diseases a study of this complex problem was begun at the Cleveland Clinic in 1957. Animals were given radioactive serotonin, and new metabolites including acetyl serotonin were identified. Other studies also indicated that whereas the catecholamines became inactivated, serotonin and its derivatives, in some respects, became more active when O-methylated.
Attention then became . . .