| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1995: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Research Abstract |
To evaluate the changes in melatonin synthesis during peripubertal period in the female rat and to determine the effects of ovarian steroid hormones on melatonin synthetic activity. Pineal levels of tryptophan, 5-hydroxytryptamine (5-HT), melatonin and norepinephrine, and pineal activities of N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) were determined in female rats in the mid-dark during the daily light : dark cycle. Paralleling pineal growth, melatonin levels increased with age until 6 weeks of age, when vaginal opening was found in 66.7% of the rats, threafter, melatonin levels decreased significantly until 8 weeks of age, when vaginal opening had occured in all rats. In contrast, norepinephrine had reached mature levels at 4 weeks of age. Bilateral ovarictomy at 4,6 and 8 weeks of age led to significant increases in levels of melatonin and 5-HT,and a significant decrease in level of tryptophan 2 weeks after the procedure. After ovariectomy at 6 weeks of
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age 5-HT levels consistently increased and tryptophan levels consistently decreased for 6 weeks. Melatonin levels, in contrast, increased for 2 weeks before decreasing and reaching control levels 6 weeks sfter ovariectomy. The daily subcutaneous injection of estradiol benzoate (1.0,20.0mug) for two weeks in ovariectomized rats resulted in significant decrease in melatonin and 5-HT levels and a significant increase in the tryptophan level 2 weeks after ovariectomy. Progesterone (200mug/day) administered for 2 weeks had no signigicant effect on levels of melatonin, 5-HT or tryptophan. Norepinephrine levels were un affected by such treatment. Changes in pineal NAT activity was similar to that in melatonin.
Present study demonstrated that estrogen, but not progesterone, can modulate the pineal snthesis of melatonin in peripubertal female rats. The decline in melatonin synthesis observed in the pubertal period may be related to the increasing levels of endogenous estrogen secreted by the maturring ovaries. The suppressive effect of estrogen on melatonin synthesis may be, in part, mediated by modulation of NAT activity. Less
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