PubMed Health⌕ Search

Biomedical subjects

D P Cardinali

Publications and source records attributed to D P Cardinali.

At least 235 records · Page 13Linked to original sources

Nuclear receptor estrogen complex in the pineal gland. Modulation by sympathetic nerves.

Pineal nuclear receptor estradiol complex determined by the 3H-estradiol exchange assay exhibited a Kd = 0.42 nM. Its concentration was maximal at proestrus and after administering 2-20 microgram of estradiol to spayed rats. It was also detected in 6-day-old rats, before full maturation of pineal sympathetic nerves is attained. Superior cervical ganglionectomy caused nuclear receptor estrogen complexes (NREC) to decrease by 48 and 65% 5 and 14 days later; estradiol administration brought about increases of complex levels (1.9-2.3-fold) which were significantly smaller than in control or decentralized rats (3.4-3.9-fold). The time course of accumulation and retention of nuclear complexes was not affected by ganglionectomy. Isoproterenol restored the basal levels of NREC, but inhibited the effects of estradiol on complex accumulation; propranolol, administered simultaneously with estradiol also inhibited estrogen effects on the pineal. Estradiol incubation in vitro increased pineal nuclear receptor hormone levels and enhanced the conversion of serotonin into melatonin and 5-methoxytryptophol; no changes in hydroxyindole-O-methyl transferase (HIOMT) activity were detected. These data support the conclusion that accumulation and retention of pineal NREC are under partial dependence upon sympathetic nerves.

Acetylserotonin O-Methyltransferase↗

Changes in (3H)leucine incorporation into pineal proteins following estradiol or testosterone administration: involvement of the sympathetic superior cervical ganglion.

Pineal denervation by superior cervical ganglionectomy (Gx) decreased high affinity binding of estradiol (E2) to the pineal cytosol of female rats and of testosterone to the cytosol of male rats by 40 and 26% and by 75 and 80%, 5 and 14 days after sugery; hormone binding remained unchanged up to 24 h after surgery. Binding to the nuclear fraction decreased sigificantly by 2 weeks after incorporation of (3H) leucine into pineal proteins in Gx. A single injection of E2 (mug) to testosterone propionate (TP) (500 mug) failed to increase the Gx rats when injected 1 or 5 days after surgery. Significant increases were observed in sham-operated controls or in rats subjected to bilateral decentralization of ganglia; however on the 5th day an impairment was observed in hormone ability to enhance [3H]leucine incorporation in decentralized rats. The administration of isoproterenol 19 and 3 h before sacrifice replenished pineal-binding sites for E2 and testosterone in Gx rats, but failed to restore the responsiveness of denervated pineals to hormone administration. Moreover, E2 or TP treatment blocked the increase in labeled amino acid incorporation into proteins brought about by isoproterenol per se. The administration of propranolol 2 and 7 h after hormone injection decreased the ability of E2 and TP to enhance [3H]leucine incorporation by 55 and 41%, respectively. Tyrosine hydroxylase activity of the superior cervical ganglia decreased by 36 and 41% 6 h after E2 or TP administration, and by 43 and 47% after 3 daily injections of the hormones, whereas pineal tyrosine hydroxylase remained unchanged. Hormone treatment for 3 days increased the in vitro uptake of norepinephrine by the ganglia but did not affect uptake in the pineal gland. These data indicate that the integrity of neurons of the superior cervical ganglia is an absolute requirement for E2 and testosterone to enhance [3H]leucine incorporation into pineal proteins in rats.

Adrenergic beta-Antagonists↗

Lack of effects of testosterone on norepinephrine turnover and tyrosine hydroxylase activity of the rat vas deferens and epididymis.

To test the effects of testosterone on some aspects of the metabolism of norepinephrine (NE) in short adrenergic neurons of the male genital tract, orchiectomized rats received 500 mug of testosterone propionate twice daily for up to 18 days. Androgen treatment did not affect the levels, uptake or efflux of NE nor modified the activity of tyrosine hydroxylase in the vas deferens and epididymis. Likewise, formaline-induced fluorescence and ultrastructure of nerve endings remained unchanged after testosterone administration. These data suggest that short adrenergic neurons of male genital tract are relatively insensitive to androgens.

Animals↗

Time-dependence of estradiol effects on protein synthesis in the rat neurohypophysis.

The incorporation of 3H-leucine into neurohypophyseal proteins was measured in vitro, 24 h after the administration of a single dose of estradiol (0.3 mug) to castrated female rats. Estradiol treatment caused a significant increase of 3H-leucine incorporation into proteins of the posterior lobe. The effects of estradiol depended largely upon time injection. Rats injected at 06.00 h, i.e., at the end of the dark period exhibited a 74% increase in protein synthesis, whereas rat injected at 14.00 h, i.e., at the middle of the light period only showed a 30% of increase.

Animals↗

Effects of melatonin treatment and environmental lighting on the ultrastructural appearence, melatonin synthesis, norepinephrine turnover and microtubule protein content of the rat pineal gland.

Melatonin administration or exposure of rats to darkness for two weeks induced comparable changes in pineal ultrastructure, compatible with a generalized organ's activation. These include an increased number of ribosomes, procentrioles and microtubules, prominent nucleoli and Golgi apparatus, and annulate lamellae. Melatonin treatment resulted in a dose-dependent increase of hydroxyindole-O-methyl transferase and serotonin-N-acetyltransferase activities. In addition it increased by 85% the colchicine binding capacity of pineal homogenates, an estimation of the microtubule protein content of the gland. Pineal norepinephrine turnover was not affected by melatonin treatment. These data indicate that the pineal itself is a target organ for exogenously administered melatonin. Key words: Pineal gland, melatonin, norepinephrine, tubulin.

Acetylserotonin O-Methyltransferase↗

Melatonin effects on brain. Interaction with microtubule protein, inhibition of fast axoplasmic flow and induction of crystaloid and tubular formations in the hypothalamus.

[3-H]Melatonin administered in vivo in the rat cisterna magna became associated with a vinblastine-precipitable protein. Melatonin treatment decreased microtubule protein content by 44% in the arcuate-median eminence region and by 19% in the remaining hypothalamic block, being without significant effect on the cerebral cortex. Superior cervical gangliectomy but not pinealectomy increased microtubule protein content of the rat hypothalamus. Norepinephrine brought about a significantly greater decrease in hypothalamic microtubule protein levels of ganglionectomized rats than in sham-operated or in ganglionectomized-pinealectomized animals. Melatonin treatment induced in most of the axons ending in the pericapillary zone of the rat median eminence crystaloid and tubular formations. Rapid axonal transport in retinal ganglion cells of rabbits was inhibited to the extent of 71.9 and 87.2% by previous exposure to 1.5 of 15 mu g of melatonin intravitreally; melatonin did not affect retinal protein synthesis in this experimental model. These results suggest that melatonin interacts significantly with microtubule or actin-like protein in brain.

Animals↗

Effects of melatonin on neurotransmitter uptake and release by synaptosome-rich homogenates of the rat hypothalamus.

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.

Animals↗

Effects of environmental lighting, superior cervical ganglionectomy and adrenergic drugs on microtubule protein levels of the rat hypothalamus.

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.

Animals↗

Changes in hypothalamic neurotransmitter uptake following pinealectomy, superior cervical ganglionectomy or melatonin administration to rats.

Rats subjected to pinealectomy or to pinealectomy plus bilateral superior cervical ganglionectomy exhibited depressed serotonin uptake by hypothalamic synaptosomes; norepinephrine, dopamine or glutamate uptake was not affected by any of the surgical procedures. Treatment with melatonin resulted in inhibition of hypothalamic serotonin accumulation but it did not modify the uptake of norepinephrine, dopamine or glutamate. These data suggest a relationship between the pineal gland and the serotoninergic nerve endings of the hypothalamus.

Animals↗