Gonadal steroids as modulators of the function of the pineal gland.
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Biomedical subjects
Publications and source records attributed to C A Nagle.
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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.
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.
The pineal has undergone marked changes as vertebrates have evolved from amphibians to mammals. The amphibian pineal is a photoreceptive organ which sends nervous information to the brain via pineal nerves: the mammalian and avian pineal have no direct connections to the CNS and their metabolism is controlled by an indirect pathway involving their peripheral sympathetic nerves. In addition, the pinealocytes of some birds also function as photoendocrine transducers, i.e., they convert a photic input reaching them directly through the skull into a hormone output. Through the secretion of melatonin and of some as yet undefined low molecular weight peptides, the pineal participates in the control of other neuroendocrine rhythms such as seasonal cycles in gonadal function.
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