title: Circadian rhythms of human pineal melatonin, related indoles, and beta adrenoreceptors: post-mortem evaluation.
abstract: Human pineal glands obtained from 77 post-mortem sources from various age groups and times of death were used to examine the 24-hour cycle of serotonin (5-HT), melatonin, N-acetylserotonin (NAS), and beta adrenoceptor density. Pineal glands were divided sagittally and a single half was used to measure 5-HT, NAS, and melatonin concentrations, while the remaining half from the same gland was employed to assess changes in the density of beta adrenoceptors on partially purified membranes. The results show that density of pineal beta adrenoceptors was relatively constant between midnight and 18.00 h and became significantly higher between 18.00 and 20.00 h as measured by ligand saturation binding experiments using (125-I) iodocyanopindolol. The receptor affinity of all of the samples assayed remained in relatively narrow range near 58 pM and only changes in the relative receptor density were apparent. The up-regulation of receptors coincided with an increase in the concentration of 5-HT that began to rise between 16.00 and 20.00 h and became maximal between 20.00 and midnight. NAS, the immediate precursor of melatonin, was also at maximal levels between 20.00 h and midnight. Both 5-HT and NAS began declining after midnight and this change corresponded to the maximal pineal gland concentration of melatonin between midnight and 4.00 h. It is therefore suggested that the up-regulation of beta adrenoceptors noted during the late afternoon and early evening hours corresponds to the increased synthesis of 5-HT and the subsequent conversion to NAS. These events are followed by the highest accumulation of melatonin after midnight and represent the synthesis of melatonin from its precursor NAS in a sequential pattern.
authors.affiliation: Department of Psychiatry and Human Behavior, Brown University, Providence, RI.
authors.forename: G F
authors.initials: GF
authors.lastname: Oxenkrug
authors.forename: G F
authors.initials: GF
authors.lastname: Anderson
authors.forename: L
authors.initials: L
authors.lastname: Dragovic
authors.forename: M
authors.initials: M
authors.lastname: Blaivas
authors.forename: P
authors.initials: P
authors.lastname: Riederer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D002648:Child; D002675:Child, Preschool; D002940:Circadian Rhythm; D005260:Female; D006801:Humans; D007211:Indoles / Q000378:metabolism*; D007223:Infant; D008297:Male; D008550:Melatonin / Q000378:metabolism*; D008875:Middle Aged; D010870:Pineal Gland / Q000378:metabolism*; D011180:Postmortem Changes; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D012701:Serotonin / Q000031:analogs & derivatives / Q000378:metabolism; D013997:Time Factors
chemical_list: D007211:Indoles; D011943:Receptors, Adrenergic, beta; D012701:Serotonin; D008550:Melatonin; C006389:N-acetylserotonin