This project investigates the environmental and physiological regulation of the pineal gland. The major new findings made within the last year are: (1) The suprachiasmatic nucleus, which appears to contain the circadian clock which drives the pineal rhythms, was found not to drive the rhythm in oxytocin in cerebral spinal fluid of a subhuman primate. This is an indication that there are multiple circadian oscillators in primates. (2) Administration of hydroxytryptophan to sheep, which elevates melatonin in the blood, also elevates melatonin and N-acetylserotonin in the sheep pineal gland. This is an indication that hydroxytryptophan is probably acting to elevate melatonin by a mass-action effect on the pineal gland. (3) The pineal Alpha1-adrenergic receptors were found to be present before nerves invaded the gland, indicating that their development was independent of innervation, and either was part of a pineal developmental schedule, or triggered by circulating messenger chemicals. (4) Environmental and neural regulation of pineal Alpha1-adrenergic receptors was demonstrated. Both constant darkness and denervation caused an increase in receptor numbers. (5) It was discovered that 2-fluoronorepinephrine and 6-fluoronorepinephrine act as alpha- and Beta-adrenergic agonists, respectively, in controlling the pineal gland. This makes it possible to prepare mixtures of fluoroderivatives to norepinephrine which have graded Alpha- or Beta- strengths.
