Rhythmic function of pineal hydroxyindole-O-methyl transferase during the estrous cycle: an analysis.

investigation (Wurtman et a!., 1968; Reiter and Sorrentino, 1970). Among several indolie compounds produced by the pineal is melatonin, a presumptive hormone which exhibits anti-gonadotropic activity in the rat and other mammals. Early work demonstrated that melatonin reversed the persistent estrus induced in rats by continuous lighting (Wurtman et al., 1964); injections of the indole decreased the incidence of estrous-type vaginal smears by about 17% (Chu et a!., 1964). More recently, Fraschini et al. (1968) have demonstrated that implants of melatonin placed in the median eminence of the hypothalamus blocked secretion of luteinizing hormone (LH) from the pituitary gland. Similarly, Karnben et a!. (1970) have shown convincingly that injection of the pineal indole into the third ventricle of the brain depressed serum LII levels for about an hour. Furthermore, when melatonin was administered into the ventricle during the “critical period” on the afternoon of proestrus in mature rats, the ovulatory surge of LH was depressed and a significant blockade of ovulation resulted (Fraschini et a!., 1971; Ying and Creep, 1973), The terminal step in the synthesis of melatonin and several other pineal indoles requires catalysis by the enzyme hydroxyindole-O-methyltransferase (IIIOMT, EC 2.1.1.4). The activity of this enzyme varies diurnally, appears to be affected by photoperiod (Axelrod et a!., 1965), and also fluctuates with the stages of the estrous cycle (Wurtman et al., 1965). In the present study, we have used the activity of this enzyme as a monitor of pineal activity in an attempt to relate the function of the gland to changes in photoperiodicity and reproductive cyclicity in the rat. We have measured the diurnal fluctuation in HIOMT activity during the estrous cycle of adult female rats and showed how these fluctuations are resolvable by a mixed-wave equation composed of at least two component rhythms whose interaction creates a “beat frequency” pattern (Mercer, 1965).