Mechanisms underlying the effects of estrogen on nocturnal melatonin synthesis in peripubertal female rats: relation to norepinephrine and adenylate cyclase.

We previously reported that estrogen modulates the nocturnal synthesis of melatonin in the pineal gland of peripubertal female rats. These effects appeared to be mediated by the modulation of N-acetyltransferase (NAT) activity. The present study assessed the mechanism underlying the effects of estrogen deficiency and stimulation on pineal melatonin synthesis in peripubertal female rats. We measured the norepinephrine levels and adenylate cyclase activity in pineal gland homogenates obtained from 4-10-wk-of-age female Sprague Dawley rats at mid-dark during the daily light/dark cycle. The animals were ovariectomized and daily s.c. administration of estradiol benzoate (E2B, 1.0 microgram/d) was initiated at 4 wk of age. Pineal norepinephrine levels increased significantly from Week 3 to 4 (P < 0.0001), and remained unchanged thereafter. Neither ovariectomy nor E2B administration significantly affected norepinephrine levels. Adenylate cyclase activity in the pineal gland peaked at 4 wk in untreated (control) rats. Ovariectomy at Week 4 led to a significant increase in adenylate cyclase activity at Week 8. At Week 10, adenylate cyclase activity returned to control levels. S.c. injection of E2B suppressed the ovariectomy-induced increase in adenylate cyclase activity to the level seen in control rats. These changes in mid-dark adenylate cyclase activity resembled those previously observed with NAT activity. The results suggest that estrogen modulates adenylate cyclase activity in the pineal gland of peripubertal female rats. The inhibitory effect of estrogen on melatonin synthesis appeared to be mediated in part, by changes in the norepinephrine-induced stimulation of pineal adenylate cyclase activity.