Until recently, investigators wishing to examine the physiology of the mammalian pineal organ could do so only by killing animals and measuring the in vitro activity of certain pineal enzymes or the biochemical composition of the organ. Such evidence was at best indirect, and what was known of human pineal physiology was perforce inferential. Now, for the first time, it is possible to make direct measurements of the pineal hormone melatonin in such body fluxes as blood, urine, and CSF; sensitive and specific bioassays and radioimmunoassays exist which yield data that are comparable to those obtained by GC-MS methods. We have established all of these assay procedures at MIT, and we intend, ultimately, to use them in a detailed study of human pineal physiology. Preliminary investigation reveals that these assay methods are equally applicable to the study of melatonin secretion and excretion in experimental animals and that rats and human subjects exhibit similarity in these functions. We propose, therefore, to perform initial studies using laboratory rats. Particular relationships to be explored include: 1) the "fine structure" of daily rhythms and the range of individual variation in melatonin secretion by highly inbred strains of rats, and the effect of sex, size, developmental stage, strain, and dietary and pharmacological factors; 2) the effects of environmental lighting on melatonin secretion, and the extent to which pineal secretory rhythms are truly circadian; and, 3) the extent to which physiologic changes in blood (or urine) melatonin levels parallel the previously-observed changes in the activities of the melatonin forming enzymes. These data will provide a basis for efficient utilization of volunteer human subjects in future studies.
NIH ExPorter
NIH ExPorter