Y. Okatani et al., Changes in nocturnal pineal melatonin synthesis during the perimenopausal period: Relation to estrogen levels in female rats, J PINEAL R, 27(2), 1999, pp. 65-72
To evaluate changes in melatonin synthesis during the perimenopausal period
in the female rat and to determine the effects of estrogen on melatonin sy
nthesis, pineal levels of tryptophan, melatonin and norepinephrine and acti
vities of N-acetyltransferase (NAT)and hydroxyindole-O-methyltransferase (H
IOMT) 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 (E-2) concentrations were also determined. Pineal melatonin leve
ls significantly decreased from month 4-12 and significantly increased from
month 12-16, decreasing thereafter. Serum E-2 concentrations significantly
decreased from month 12-16, and remained low thereafter. No significant ch
anges in tryptophan or norepinephrine were seen. NAT activities paralleled
the time course of changes in melatonin. HIOMT activities decreased gradual
ly from month 4-24. Subcutaneous implantation of an E-2 capsule between mon
ths 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 i
ncreases in the levels of melatonin and NAT activity. These findings repres
ent a temporal increase in pineal melatonin synthesis during the perimenopa
usal period, and suggest that the increase in melatonin synthesis activity
at that time might result from decreasing levels of endogenous estrogen. Th
e effect of estrogen on melatonin synthesis appeared to involve modulation
of NAT activity.