Changes in nocturnal pineal melatonin synthesis during the perimenopausal period: Relation to estrogen levels in female rats

To evaluate changes in melatonin synthesis during the perimenopausal period in the female rat and to determine the effects of estrogen on melatonin synthesis, pineal levels of tryptophan, melatonin and norepinephrine and activities of N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) were determined. Homogenates for assay were prepared from the pineal glands of female virgin Sprague-Dawley rats between 4 and 24 months of age in the middle of the dark period of a daily light/dark cycle. Serum 17 beta-estradiol (E2) concentrations were also determined. Pineal melatonin levels significantly decreased from month 4 12 and significantly increased from month 12 16, decreasing thereafter. Serum E2 concentrations significantly decreased from month 12-16, and remained low thereafter. No significant changes in tryptophan or norepinephrine were seen. NAT activities paralleled the time course of changes in melatonin. HIOMT activities decreased gradually from month 4 24. Subcutaneous implantation of an E2 capsule between months 12 and 16 resulted in significant decreases in levels of melatonin and NAT activity at month 16. Ovariectomy at month 4 or 12 led to significant increases in the levels of melatonin and NAT activity. These findings represent a temporal increase in pineal melatonin synthesis during the perimenopausal period, and suggest that the increase in melatonin synthesis activity at that time might result from decreasing levels of endogenous estrogen. The effect of estrogen on melatonin synthesis appeared to involve modulation of NAT activity.