Changes in the Enzymatic Synthesis of Melatonin in the Pineal During the Estrous Cycle

The activity of hydroxyindoleO-methyl transferase (HIOMT) in the rat pineal gland varies 2-fold during the estrous cycle. HIOMT activity is greatest during diestrus, and falls during proestrus and estrus. Neither estradiol administration nor oophorectomy reproduces the effect of the estrous cycle. Estradiol administration causes a decrease in pineal weight. {Endocrinology 76: 798, 1965) p IS considerable evidence that the A mammalian pineal gland contains factors which influence gonad growth and function when administered to experimental animals (1-3). Two methoxyindoles present in the pineal, melatonin (4, 5) and methoxytryptophol (6), have been shown to depress the incidence of vaginal smears showing estrous phases in the rat. These compounds are synthesized by an enzyme, hydroxyindoleO-methyl transferase (HIOMT) (7), which has been found only in the pineal (8). Melatonin appears to be released by the pineal into the circulation (4, 9, 10), and is selectively concentrated within the ovary (10). It has recently been shown that the capacity of the rat pineal gland to synthesize melatonin is controlled indirectly by environmental lighting (11). Information about the state of lighting is transmitted to the pineal by a neural pathway, involving the retinas and sympathetic nerves which originate in the superior cervical ganglia (12). The activity of HIOMT in the rat pineal normally follows a circadian rhythm: it is highest at night, and falls during the day (13). This rhythm appears to be lightdependent; it is extinguished in the absence of diurnal photoperiodicity, or following blinding (13). When rats are kept in continuous light or darkness, the cyclic changes Received November 20, 1964. 1 Department of Pathologic Anatomy. in HIOMT are exaggerated. Dark-treated rats have 3-10 times more enzyme activity than litter mates kept in continuous light (11). On the basis of these observations, it has been suggested that one function of the rat pineal is to serve as a neuroendocrine transducer, which converts a neural input {e.g., information about environmental lighting) into an endocrine message (14). This endocrine response (methoxyindole synthesis and release) then influences gonad function (15). This hypothesis is consistent with recent observations that sympathetic denervation of the rat pineal, like blinding, blocks the "early response" of the rat ovary to light (15). If the rodent pineal is involved in the regulation of cyclic gonadal function, then it is possible that its level of synthetic activity might vary with the estrous cycle. Zweens reported that the amount of Sudan Black B-positive material in the rat pineal (estimated histochemically, and thought to represent phospholipid) was elevated during diestrus or following bilateral oophorectomy (16). Quay observed that the content of serotonin (a precursor of the methoxyindoles) in the rat pineal varied 5to 6-fold with a circadian cycle (17). At the same times on succeeding days of the estrous cycle, small differences were observed in pineal serotonin levels; however, no pattern was evident in these changes to suggest that they were related to the cycle in a regular way. This report shows that the enzymatic