Effect of estrogen on melatonin synthesis in female peripubertal rats as related to adenylate cyclase activity

To determine the mechanism for the modulatory effect of estrogen on melatonin synthesis, we evaluated the effects of estrogen on the activity of adenylate cyclase in female Sprague-Dawley rats of peripubertal age. Adenylate cyclase activity was measured in homogenates of pineal glands from rats aged 3 and 10 weeks in the mid-dark and in the mid-light. Ovariectomy was performed and a subcutaneous injection of estradiol benzoate (E2B) was administered daily starting at the age of 6 weeks. A peak in adenylate cyclase activity in the pineal gland was observed in untreated (control) rats with intact ovaries at 4 weeks. Ovariectomy at week 6 led to significant increases in the activity of adenylate cyclase at week 8. At week 10, adenylate cyclase activity resembled that of control animals. The subcutaneous injection of E2B (1.0 microg/day) suppressed the increase in adenylate cyclase activity induced by ovariectomy, similar to the level seen in control rats with intact ovaries. The changes in the mid-light activity of pineal adenylate cyclase resembled that seen at the mid-dark with the value being significantly lower than that observed in the mid-dark. Such changes in the mid-dark activity of adenylate cyclase resembled those observed with N-acetyltransferase (NAT) at the same time, as previously described. Results suggest that estrogen modulates adenylate cyclase activity in the pineal gland of peripubertal female rats. The decline in melatonin synthesis during puberty may be related to an increase in estrogen level. The inhibitory effect of estrogen on melatonin synthesis appeared to be mediated by a change in the norepinephrine-induced stimulation of pineal adenylate cyclase activity.