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Seasonal variation of gonadotropins and gonadal steroids receptors in the human pineal gland.

Recently abnormal melatonin secretion was demonstrated in hypogonadal male patients which was normalized during testosterone administration. These results suggested that both gonadal steroids and gonadotropins may modulate melatonin secretion, probably by activating specific receptors in the pineal gland. We used immunohistochemistry to localize luteinizing hormone, follicle stimulating hormone, estrogen and androgen receptors in human pineal glands. Tissues were obtained at autopsy from 53 adult males (aged 19-94 years) over a period of 1 year. Positive staining for the four types of receptors was evident in all 53 specimens examined. The percent of positively stained cells revealed a significant seasonal variation of gonadotropin receptors with higher values in the winter than in the summer. Day-night difference was evident only for follicle stimulating hormone-receptors during the summer and winter, with higher values at night. Androgen receptors and estrogen receptors were present in all specimens but did not reveal day-night or seasonal variations. These data demonstrate the presence of gonadotropin and gonadal steroid receptors in the human pineal gland. Gonadotropin receptors exhibited seasonal variation with higher values in the winter.

Adult↗

5-Methoxytryptophol rhythms in the chick pineal gland: effect of environmental lighting conditions.

5-Methoxytryptophol (5-ML) rhythms were studied in the pineal glands of chicks which were adapted to three different lighting conditions: 12 h light: 12 h dark (LD), constant darkness (DD) and continuous light (LL). Pineal glands of chicks kept under LD conditions exhibited rhythmic fluctuations in 5-ML content. 5-ML levels were low (18+/-2 pg/pineal) during the dark phase of the cycle, they increased approximately 9-fold at the end of the dark phase, and remained high (176 +/-6 pg/pineal) throughout the light period. This pattern of 5-ML content also persisted under conditions of DD, indicating that the 5-ML rhythm is circadian in nature. This is the first evidence of circadian rhythmicity of 5-ML. Pineal 5-ML levels in chicks kept under LL were high (168+/-8 pg/pineal), but did not fluctuate in a rhythmic fashion. Under LD and DD, but not LL, the rhythm of 5-ML in the chick pineal is 180 degrees out of phase with the rhythm of melatonin biosynthesis, an observation suggesting that, at least in this species, the pineal production of these two hormones may be inversely correlated.

Animals↗

Effects of sex and gonadal steroids on arginine vasotocin and mesotocin in the pineal gland and neurohypophysis of White Leghorn fowls.

1. Pineal and neurohypophysial arginine vasotocin (AVT) and mesotocin (MT) were measured in White Leghorn hens, cockerels and castrated males treated with either testosterone propionate (TP) or oestradiol benzoate (EB) (n = 10/group). The lighting regimen was 14 h light: 10 h dark, supplied by natural diffused sunlight and incandescent bulbs. 2. Both AVT and MT were detected in the pineal gland of all the chickens. 3. There was no significant effect of either sex or treatments on pineal MT. 4. Females had about 4 times more pineal AVT than males, regardless of their treatment. There was no effect of the treatments on pineal AVT in the males. 5. No sexual difference in neurohypophysial AVT was detected, but the neurohypophysis of the castrated males treated with EB contained less AVT than the neurohypophysis of the intact males. 6. Intact males had about twice as much MT in the neurohypophysis as females. Castrated males treated with either TP or EB had similar concentrations of neurohypophysial MT, which were lower than that of the intact males, but higher than that of the females.

Animals↗

Diencephalic origin of the pineal gland of the chicken embryo.

In the present paper, the diencephalic origin of the chick pineal gland was analyzed by a series of experiments: prosencephalic substitution; in vitro culture of isolated diencephalons; and total or partial excission of the diencephalic roof. The results indicate that the differentiation of the chick pineal gland in the rooof of the third ventricle is not influenced by the neighbouring brain vesicles and is of diencephalic origin. Moreover, in order to obtain chick embryos with pineal agenesia, the whole diencephalic roof has to be removed.

Animals↗

Stimulation of serotonin-N-acetyltransferase activity in the pineal gland of the mongolian gerbil (Meriones unguiculatus) by intracerebroventricular injection of vasoactive intestinal polypeptide.

There is ever-increasing evidence that intrapineal peptides have an important role in the modulation of pineal melatonin synthesis. In the pineal gland of the Mongolian gerbil (Meriones unguiculatus), we have previously shown the presence of VIP-immunoreactive nerve fibers as well as pinealocytic VIP receptors. To assess the functional significance of these findings, 10 microliters of a 1 microM or 1 nM solution of VIP were injected into the lateral ventricle of gerbils over a period of 10 min. Animals were killed 1.5 hr after injection, and the superficial pineal glands were excised and assayed for N-acetyltransferase (NAT) activity. Injection of the 1 microM VIP solution stimulated the NAT activity to values four times the control values. The results are compatible with an in vivo influence on the pineal gland indole metabolism of the nonsympathetic VIP-containing nerve fibers via VIP-receptors present in the gland.

Acetyltransferases↗

[Usefulness of melatonin in the diagnostics and therapy of pineal gland and brain neoplasms].

Melatonin or N-acetyl-5-methoxytryptamine is mainly produced by pineal gland and exhibits characteristic diurnal rhythm of synthesis and secretion with the highest levels at night and low levels during a day. For several years the knowledge of pineal gland and its hormone was rather poor. It was last years when knowledge of the role of melatonin in health and different diseases was developed. Nowadays we are aware that melatonin plays important role in diagnosis and therapy of several diseases, and may be helpful factor also in neurosurgery. Author presents the review of the present knowledge on the role of melatonin in diagnosis of pineal region pathology and treatment of brain tumors.

Brain Neoplasms↗

Type II thyroxine 5'-deiodinase activity in the rat brown adipose tissue, pineal gland, Harderian gland, and cerebral cortex: effect of acute cold exposure and lack of relationship to pineal melatonin synthesis.

The effect of acute cold exposure for 6 hours on nocturnal type II thyroxine 5'-deiodinase (5'-D) activity was studied in brown adipose tissue (BAT), Harderian gland, cerebral cortex, and pineal gland of the rat. Moreover, the effect of iopanoic acid (IOP), a potent inhibitor of 5'-D activity, on both pineal N-acetyltransferase (NAT) activity and melatonin content in rats maintained in a cold environment was also examined. Results show that acute cold exposure significantly increases 5'-D activity in BAT but not in either the pineal gland, Harderian gland, or cerebral cortex. In all tissues, the injection of IOP reduced dramatically 5'-D activity, while exposure of the animals to light at night reduced 5'-D activity in pineal gland but not in either the Harderian gland or BAT while light exposure at night increased cerebrocortical 5'-D activity. Cold exposure did not change either pineal NAT activity or the melatonin content of the gland. Finally, when pineal 5'-D activity was inhibited by IOP treatment, neither nocturnal pineal NAT activity nor melatonin content was affected.

Adipose Tissue↗

Cyclic AMP increases hydroxyindole-O-methyltransferase mRNA levels in the chicken pineal gland, but is not required for circadian rhythmicity of this transcript.

Hydroxyindole-O-methyltransferase (HIOMT) plays an important role as the final enzyme in the synthesis of melatonin. In the chicken pineal gland, HIOMT mRNA concentration exhibits a circadian rhythm with a threefold peak at midday. The present study sought to evaluate the possible role of cyclic AMP in this transcriptional rhythm. In cultured pineal glands from 4-day-old chicks, cyclic AMP analogs and the adenylate cyclase activator, forskolin, increased HIOMT mRNA levels twofold to threefold in a dose-dependent manner. Vasoactive intestinal polypeptide increased HIOMT mRNA levels by 50%. Actinomycin-D chase experiments indicated that cyclic AMP did not affect the stability of HIOMT mRNA, thus providing indirect evidence that the effect of cyclic AMP was exerted at transcriptional level. In cultured pineal glands from 11 days embryos, HIOMT mRNA levels failed to respond to cyclic AMP. However, a daily rhythm of HIOMT mRNA, with an endogenous component in constant darkness was clearly observed at this developmental stage. This observation indicates that cyclic AMP is not required for circadian rhythmicity of HIOMT gene transcription.

Acetylserotonin O-Methyltransferase↗

Regulation of "peripheral-type" binding sites for benzodiazepines in the pineal gland.

The density of "peripheral-type" binding sites for benzodiazepines (PBS) in the rat pineal gland was reduced by approximately 50% three weeks after superior cervical ganglionectomy or exposure to constant light; the apparent affinity of [3H]Ro 5-4864 (the prototype ligand for these sites) remained unchanged. In contrast, neither the density of PBS nor the apparent affinity of [3H]Ro 5-4864 for these sites was altered in cerebral cortex by these procedures. The demonstration that PBS density is under neural control in the pineal gland suggests that these sites may have a physiologic role. The high density of PBS in pineal (approximately 24 pmol/mg protein) suggests that this tissue may be a useful model to study both the physiologic and pharmacologic function of these sites.

Animals↗

Distribution of calcification within the pineal gland.

The distribution of calcification in the normal pineal gland was investigated by a macroradiographic in vitro technique. The centre of calcification in 72 out of 73 glands studied was within 2 mm of the mid-line of the gland. In one gland it lay 2.6 mm from the mid-line. These findings explain the accepted normal limits for pineal calcification on the standard semi-axial projection of the skull of up to 2 mm to either side of the mid-line and the occasional measurement in excess of this in normal subjects.

Adult↗

Chick retina and pineal gland differentially respond to constant light and darkness: in vivo studies on serotonin N-acetyltransferase (NAT) activity and melatonin content.

Oscillations in serotonin N-acetyltransferase (NAT) activity and melatonin content were investigated in retina and pineal gland of chicks kept for 5 days in constant darkness (DD) or continuous light (LL). Under DD the rhythm of the pineal melatonin biosynthesis resembled that found under diurnal illumination (LD), whereas in the retina DD resulted in significant elevations of NAT activity and melatonin level during subjective light. A low-amplitude rhythm of retinal NAT activity continued under LL with a period close to 24 h. In the pineal gland, light exposure suppressed the level of NAT activity and melatonin content (an effect being substantially weaker than that observed in retina), delayed the first peak of NAT activity by 3 h, and prolonged the rhythm's period to about 26 h. Our data suggest the existence of some differences in the activity of circadian oscillators that regulate the melatonin generating system in the retina and pineal gland of chick.

Animals↗

The human pineal gland responds to stress-induced sympathetic activation in the second half of the dark phase: preliminary evidence.

Previous reports by our group and by others showed that the human pineal gland is unresponsive to stress-induced systemic sympathetic activation either during the day or 3 hrs after the beginning of darkness. In the present study, we investigated whether a longer period of dark exposure is required to demonstrate a stimulatory effect of stress-induced sympathetic activation on the human pineal gland. For this purpose, plasma melatonin levels were measured in six healthy men (aged 25-34 yrs) both in resting condition and before and after a physical exercise performed between 02.40 and 03.00 h, 30 min after exposure to bright light (2000 lux). Light exposure lasted from 02.10 h up to 04.00 h. The exercise consisted in bicycling on a bicycle ergometer at 50% of the personal maximum work capacity (MWC) for 10 min, followed by another 10 min of bicycling at 80% of the MWC. In the same subjects, plasma melatonin levels were measured also without exposure to light and with no exercise (control dark condition). The results showed that physical exercise, although inducing a rapid and short-term general sympathetic activation (as shown by significant changes in cardiovascular parameters) was able to increase light-depressed plasma melatonin levels only 5 hrs after the end of the stress (p < 0.0001, group X time interaction, two-way ANOVA with repeated measures). These findings suggest that the human pineal gland is responsive to systemic sympathetic activation induced by physical stress in the second half of the dark phase.

Adult↗

The pineal gland of the trumpet-tailed rat (Octodon degus).

The structure and ultrastructure of the pineal gland of the degu or trumpet-tailed rat (Octodon degus), a rodent inhabiting tropical-equatorial areas, was examined under light and electron microscopy. On the basis of its form, size, and location, the pineal gland of the degu is classified as a proximal or "A" type. The connective tissue appeared poorly developed and the gland contained non-fenestrated capillaries. A single population of typical pinealocytes was found. In addition, a small number of glial cells and cells with electron dense bodies appeared scattered throughout the gland. Cells with dense granules were found isolated or forming small groups always in close proximity to blood vessels. Numerous sympathetic nerve fibers with small dense-core vesicles were found. Also, some myelinated nerve fibers were observed. The physiological significance of the presence of large electron-dense granules in some pineal cells and their particular location around the blood vessels in discussed.

Animals↗

Studies on the role of the pineal gland in the regulation of TSH secretion in postpuberal male rats.

The role of the pineal gland in the regulation of thyroid-stimulating hormone (TSH) secretion was studied in postpuberal male rats using 12:12 h light:dark cycles. Pinealectomy, performed 3--4 days before decapitation, had no effect on the basal or thyrotropin-releasing hormone stimulated TSH secretion, but significantly decreased the cold-induced TSH response both at noon and at midnight. Neither hypothalamic thyrotropin-releasing hormone concentrations nor serum thyroid hormone levels were affected by pinealectomy. Melatonin injected intravenously (1 and 10 mg/kg) or intracerebroventricularly (5 and 50 microgram/rat) had no effect on the basal or cold-stimulated TSH levels, neither was the thyrotropin-releasing hormone induced (50 and 125 ng/rat i.p.) TSH response modified by melatonin (1 mg/kg i.v.). Arginine vasotocin (1 and 100 ng/rat) given intracerebroventricularly had no effect on the basal or cold-stimulated TSH secretion. These results suggest that the pineal has no influence on the basal activity of the hypothalamus-pituitary-thyroid system, but it seems that the cold-induced TSH response depends to a considerable degree on the intact pineal gland.

Animals↗

Rod outer segment membrane guanylate cyclase type 1-linked stimulatory and inhibitory calcium signaling systems in the pineal gland: biochemical, molecular, and immunohistochemical evidence.

Recent evidence indicates the presence of a novel alpha(2D/A)-adrenergic receptor (alpha(2D/A)-AR) linked membrane guanylate cyclase signal transduction system in the pineal gland. This system operates via a Ca(2+)-driven rod outer segment membrane guanylate cyclase (ROS-GC). In the present study, this transduction system has been characterized via molecular, immunohistochemical, and biochemical approaches. The two main components of the system are ROS-GC1 and its Ca(2+) regulator, S100B. Both components coexist in pinealocytes where the signaling component alpha(2D/A)-AR also resides. The presence of ROS-GC2 was not detected in the pineal gland. Thus, transduction components involved in processing alpha(2D/A)-AR-mediated signals are Ca(2+), S100B, and ROS-GC1. During this investigation, an intriguing observation was made. In certain pinealocytes, ROS-GC1 coexisted with its other Ca(2+) modulator, guanylate cyclase activating protein type 1 (GCAP1). In these pinealocytes, S100B was not present. The other GCAP protein, GCAP2, which is also a known modulator of ROS-GC in photoreceptors, was not present in the pineal gland. The results establish the identity of an alpha(2D/A)-AR-linked ROS-GC1 transduction system in pinealocytes. Furthermore, the findings show that ROS-GC1, in a separate subpopulation of pinealocytes, is associated with an opposite Ca(2+) signaling pathway, which is similar to phototransduction in retina. Thus, like photoreceptors, pinealocytes sense both positive and negative Ca(2+) signals, where ROS-GC1 plays a pivotal role; however, unlike photoreceptors, the pinealocyte is devoid of the ROS-GC2/GCAP2 signal transduction system.

Animals↗

Demonstration of action-potential-producing cells in the rat pineal gland in vitro and their regulation by norepinephrine and nitric oxide.

There is evidence that sympathetically innervated mammalian pineal glands contain cells that exhibit action potentials. It is unknown whether ex vivo pineal glands deprived of their nervous input are still capable of firing. In the present study, multiple-unit recordings from rat pineals revealed spontaneously active cell clusters with a mean firing frequency of 1.5 +/- 0.3 Hz which could be abolished by tedrodotoxin. Regularly firing clusters showed no inherent periodicity in the minute range, whereas rhythmical clusters with periodically repeated bursts had period lengths of 12.6 min (day) and 9.5 min (night). Superfusion of norepinephrine reduced the firing frequency of both cluster types, or had no effect, and the rhythmical clusters became regular. The effects of norepinephrine appear to be mediated via beta-adrenoceptors because isoproterenol, a beta-agonist, had the same effect as norepinephrine and as the alpha-agonist phenylephrine was without effect. Evidence was obtained that the inhibitory effect of norepinephrine may be mediated by nitric oxide, which appears to affect the electrical discharge of the cells directly or indirectly through cGMP. It is discussed whether the spontaneously active pineal cells represent an intrapineal oscillator or are driven by an intrinsic oscillator which has yet to be defined.

8-Bromo Cyclic Adenosine Monophosphate↗

The role of the pineal gland in seasonality.

The life time reproductive performance of 2 flocks of Merino crossbred ewes pinealectomized at 7-60 days of age, and maintained in South Australia did not differ from that of sham-operated control animals kept in the same flocks. The pineal gland is therefore not a major determinant of reproductive success, but a role for the pineal in adjusting breeding activity to season is not excluded. It was confirmed that pineal denervation of adult ewes by cranial sympathectomy could have disruptive effects and evidence of a seasonal change in pineal function was obtained from studies of plasma levels of melatonin, a putative pineal hormone, and a pineal peptide with gonadotrophin releasing activity. That melatonin stems mainly, but not exclusively, from the pineal gland was confirmed by studies of urinary excretion values. Adult Merino ewes produced 39-90 micrograms melatonin/day, mostly (80%) during the dark period, whereas pinealectomized animals produced less than one-fifth this amount. A link was provided between the pineal gland and diet. Melatonin and other 5-methoxyindoles influenced the activity of alpha-chymotrypsin and may regulate the availability of precursor substances required for the synthesis of neurotransmitters important in reproduction.

Animals↗

[Primary leiomyosarcoma of the pineal gland--a case report].

Primary sarcoma in the central nervous system is rare. From 1954 to 1986, 1417 neoplasms of the central nervous system were treated in our hospital and only one case of primary leiomyosarcoma of the pineal gland was seen. The patient, a forty-seven year old man, had diplopia for 2 months, headache and ataxia for 2 weeks before admission. The CT scan showed a space occupying lesion in the pineal gland. During operation, a mass, 3 x 2.5 x 2 cm in size, was found in the pineal and subtotal resection was performed. The pathological diagnosis of primary leiomyosarcoma of the pineal gland was established. The patient died the next year of the operation. Finally, the histogenesis, clinical manifestations, diagnosis and differential diagnosis are discussed with a review of literature.

Brain↗