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Preincubation of synaptosome-rich homogenates of rat hypothalamus with melatonin resulted in significant decreases of norepinephrine, serotonin, dopamine and glutamate uptake. Melatonin inhibition was noncompetitive; apparent Km's of initial uptake processes were: (2.5 +/- 0.3) x 10(-7) M for norepinephrine, (2.6 +/- 0.3) x 10(-7) M for serotonin, (2.4 +/- 0.4) x 10(-7) M for dopamine and (1.0 +/- 0.3) x 10(-7) M for glutamate. Apparent Ki's for melatonin inhibition of transmitter uptake were: 0.64 +/- 0.14 mM (norepinephrine), 0.23 +/- mM (serotonin), 0.51 +/- 0.08 mM (dopamine) and 1.21 +/- 0.10 mM (glutamate). Transmitter release evoked by increasing [K+] in medium to 30 mM was augmented by melatonin in a dose-dependent manner. Maximal effects were observed on serotonin release. Accumulation of 3H-melatonin within synaptosome-rich homogenates did not exhibit differences between 0 and 37 degrees C, indicating that the uptake of the hormone was not an active process. These results suggest that exogenously-administered melatonin may affect neurotransmitter accumulation and release in the hypothalamus by modification of the transmitter uptake mechanism rather than by competition with the transmitter for its uptake pump.

The administration of 1.5 mg of progesterone to ovariectomized estrogen-primed rats induced a surge in plasma norepinephrine (NE) preceding the pituitary LH release. The injection of reserpine (2 mg/kg) 2 h prior to progesterone completely blocked the progesterone effects on both NE and LH plasma surges. On the other hand, the adminitration of phenoxybenzamine prior to progesterone, blocked the steroid effect on LH without inhibiting the plasma NE rise. Contrarily, the alpha-blocker was able to induce a rapid increase in the amine levels 2 h after its injection. The determination of NE in the anterior hypothalamus of these rats revealed that simultaneously with the plasma NE rise induced by progesterone there was a fall in the hypothalamic amine levels. Both reserpine and phenoxybenzamine caused a depletion in the amine content of the anterior hypothalamus. In experiments measuring the arteriovenous difference in the concentration of NE across the brain following progesterone-induced LH release, it was found that most NE comes from the brain. The amine rise was evident in the jugular vein while the arterial NE concentration showed a slight increase. These findings raise the possibility that the changes in circulating NE may reflect an enhanced noradrenergic activity occurring in the brain from which the LH surge results.

In four-day cycling rats studied during the estrous cycle, the levels of circulating norepinephrine (NE) showed a sharp rise concomitant with the LH surge in the afternoon of proestrus. Following the peak, plasma NE fell rapidly to the minimum value by the morning of estrus. The administration of progesterone to ovariectomized estrogen-primed rats resulted in a surge in plasma NE levels 4 h after progesterone treatment. The maximal levels attained were 3-fold greater than baseline values, falling rapidly to reach basal values 8 h after the administration of progesterone. The amine levels remained unaffected 12-20 h later. The LH values attained a maximum 8 h after the injection of progesterone. In rats treated with estradiol benzoate (EB) followed by 0.1 ml of oil instead of progesterone, neither the NE nor the LH peak were observed. These findings are discussed with respect to the significance of increased amounts of plasma NE related to the LH surge.

Bilateral superior cervical ganglionectomy or exposure of rats to light for 10 days resulted in comparable increases in microtubule protein content in the hypothalamus. Administration of norepinephrine, L-dopa or isoproterenol decreased hypothalamic tubulin levels to a greater extent in ganglionectomized rats. A prior injection of phentolamine prevented norepinphrine's effects in intact rats and decreased but did not abolish the effect of the catecholamine in ganglionectomized animals. Phentolamine impaired L-dopa activity in intact and denervated rats as did propranolol; beta-adrenergic blockage impaired the effect of norepinephrine in denervated rats and abolished that of isoproterenol. Phentolamine plus propranolol prevented norepinephrine's effects whereas it only impaired L-dopa activity on hypothalamic tubulin content. The prior administration of actinomycin D blocked the effects of norepinephrine, L-dopa or isoproterenol. Pinealectomy abolished the isoproterenol-induced decrease in microtubule protein content and impaired that following L-dopa. These data suggest that tubulin levels of the rat hypothalamus are controlled by adrenergic transmitter via alpha- and beta-receptors, the latter involving the pineal gland.