Showing papers on "Pinealectomy published in 1981"

Melatonin inhibition and pinealectomy enhancement of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in the rat.

Abstract: The effects of the pineal hormone, melatonin, and of pinealectomy on the incidence of mammary adenocarcinoma in Sprague-Dawley rats treated with 7,12-dimethylbenz(alpha)-anthracene (DMBA) were investigated. Melatonin (2.5 mg/kg), begun on the same day as DMBA (5 mg) treatment and given daily in the afternoon for 90 days, significantly reduced the incidence of mammary tumors from 79% (control) to 20% (treated) (p less than 0.002). Rats pinealectomized at 20 days of age and treated with 7 mg of DMBA at 50 days of age had a higher incidence of tumors (88%) compared to control animals (22%). Fifteen mg of DMBA, which resulted in a higher incidence of tumors, reduced the difference between pinealectomized and control animals. Melatonin only partially reversed the effects of pinealectomy, reducing the incidence from 87% (pinealectomy alone) to 63% (pinealectomy plus melatonin); however, the tumor incidence was still lower (27%) in nonpinealectomized, melatonin-treated animals. Assessment of plasma prolactin, luteinizing hormone, follicle-stimulating hormone, estradiol, and cortisol in DMBA-treated tumor-free and tumor-bearing animals revealed a significantly lower plasma prolactin concentration [27 +/- 5 (S.E.) ng/ml] in melatonin-treated animals as compared to vehicle-treated animals [65 +/- 8 ng/ml]. The concentration of plasma prolactin was less in melatonin-treated, pinealectomized rats (55 +/- 10 ng/ml) as compared to vehicle-treated, pinealectomized animals (101 +/- 13 ng/ml). Other hormones were not affected by melatonin treatment. These data support the hypothesis that melatonin inhibits the development of DMBA-induced mammary tumors in the rat while removal of the pineal gland stimulates development of such tumors. Additionally, these experiments provide evidence that these effects may be mediated by a suppression of plasma prolactin levels.

Melatonin. A Mammalian Pineal Hormone

Abstract: PROBABLY no other organ in the body has suffered so long from a lack of its true functional recognition as the pineal gland. For more than two centuries the pineal was thought to be the seat of the soul or a vestigial remnant of the parietal eye. However, pineal research over the last 20 years has contributed significantly to unraveling the functional significance of this enigmatic endocrine gland. In this respect the isolation and characterization of melatonin by Lerner et al. (1) in 1958 constituted a landmark inasmuch as it was the first substance to be characterized in the pineal gland that reproduced many of the effects of pineal extracts or reversed the endocrine sequelae of pinealectomy. Today the pineal gland is recognized as an active functioning neuroendocrine organ that responds primarily to photic stimuli (and secondarily to hormonal signals originating in target tissues), exhibits circadian rhythms, and influences the metabolic activity of a host of endocrine glands.

Pineal and hypothalamic pacemakers: Their role in regulating circadian rhythmicity in Japanese quail

Abstract: Neither pinealectomy nor administration of melatoninvia silastic capsules had any effect on free-running circadian rhythms of locomotor activity in Japanese quail (Coturnix coturnix japonica). The quail, like the chicken, therefore differs from sparrows and starlings in which pinealectomy dramatically disrupts free-running rhythms. Nevertheless, it seems unlikely that there are fundamental differences in circadian organisation within the Class Aves. The effects of lesions within the supraoptic region (SOR) of the hypothalamus were similar to those which follow the ablation of the suprachiasmatic nuclei (SCN) in sparrows, rats and hamsters, causing the breakdown of free-running rhythms of locomotor activity, but not necessarily an arrhythmic state. The SOR and SCN appear then to have homologous functions in birds and mammals. Differences in circadian organisation, such as the degree of influence of the pineal gland and the particular photoreceptors used for entrainment, may therefore be modifications peripheral to the fundamental components of the circadian clock.

Increase in the level of retinal melatonin and persistence of its diurnal rhythm in rats after pinealectomy.

Abstract: To study the short- and long-term effects of pinealectomy on the level of retinal melatonin, male rats adapted to a photoperiod of 12 h light: 12 h darkness (with lights on at 06.00 h) were pinealectomy. In the short-term experiment, the rats were decapitated 1 week after pinealectomized. In the long-term experiment, 1 month was allowed for recovery. Melatonin was extracted from retinae and quantified by radioimmunoassay. A diurnal rhythm of retinal melatonin was found to persist after pinealectomy in both experiments. An increase in retinal melatonin was demonstrated 1 month after pinealectomy, indicating a compensatory effect on melatonin in the retinae of pinealectomized rats. Thus, biosynthesis of melatonin in the retina may be modulated through a negative feedback system.

Photoperiodic control of reproduction in olfactory-bulbectomized rats.

Abstract: 30-day-old male rats were (1) sham-operated or subjected to (2) removal of the olfactory bulbs, (3) olfactory bulbectomy and blinding (4) olfactory bulbectomy and pinealectomy or (5) olfactory bulbectomy, blinding and pinealectomy. Animals were exposed from 30 to 110 days of age to long-day (14 h of light per day) or short-day (8 h of light per day) photoperiods. The reproductive system of neurologically-intact rats was not affected by exposure to short days. Nor did bulbectomy affect the reproductive system of rats exposed to long days. However, bulbectomized, short-day rats had significantly lower body weights, reduced testicular and seminal vesicle weights and lower plasma testosterone levels than did bulbectomized, long-day rats. The effects of short-day exposure on bulbectomized rats were prevented by pinealectomy. Short-day exposure and blinding exerted similar effects in bulbectomized rats. The testes of rats from all groups contained elongated spermatids; blinding and short-day treatment had no effect on spermatogenesis. Neither mating behavior nor the number of young sired was influenced by photoperiod in bulbectomized or intact rats. Removal of the olfactory bulbs unmasks photoperiodic responsiveness in rats; the antigonadal effects of short-day exposure are mediated by the pineal gland in bulbectomized rats as in species traditionally designated photoperiodic. The mechanisms by which bulbectomy renders rats responsive to short days are considered.

The sympathetic superior cervical ganglia as peripheral neuroendocrine centers.

Abstract: The superior cervical ganglia (SCG) provide sympathetic innervation to the pineal gland, cephalic blood vessels, the choroid plexus, the eye, carotid body and the salivary and thyroid glands. Removal of the ganglia brings about several neuroendocrine changes in mammals, including the disruption of water balance in pituitary stalk-sectioned rats, and the alteration of normal photoperiodic control of reproduction in hamsters, ferrets, voles, rams and goats. These effects are commonly attributed to pineal denervation. However pinealectomy does not always mimic ganglionectomy in its neuroendocrine sequelae. This paper discusses several examples illustrating the lack of homology of ganglia and pineal removal, including the prolactin release brought about by gonadal steroids in spayed rats, the changes in drinking behaviour caused by ganglionectomy and the control of goitrogenic response to methylmercaptoimidazole in rats. All these examples indicate that SCG removal, at least as far as for neuroendocrinologists and pineal experimenters are concerned, should not be considered simply as "pineal denervation". A functionally relevant link between SCG and the hypothalamus may occur in rats inasmuch as ganglionectomy depresses norepinephrine uptake and increases the number and responses of alpha-adrenoceptors in medial basal hypothalamus. Lastly the SCG are active points of concurrency for hormone signals, as revealed by the metabolic changes induced by steroid and anterior pituitary hormones in these structures even in the absence of intact preganglionic connections, as well as by the existence of putative receptors for some of the hormones, namely, estradiol, testosterone and corticosteroids. The SCG appear to constitute a peripheral neuroendocrine center.

Persistence of circadian rhythms of melatonin and N-acetylserotonin in the serum of rats after pinealectomy.

Abstract: To study the effect of pinealectomy (Px) on the rhythms of serum indoles, male rats were adapted to 12L:12D for 2 weeks after which half of them were Px. The animals were decapitated at 4-hour intervals 1 week after operation. Melatonin (Mel) and N-acetylserotonin (NAS) were extracted and quantified by RIA. The concentrations of serum Mel and NAS were significantly reduced after Px, suggesting that the pineal contributes a significant amount of these to the blood. However, circadian rhythms of them were not abolished by Px, indicating the existence of extrapineal sources at least one of which is capable of secreting Mel and NAS with a diurnal rhythm. Retina is suspected to be an important source.

Circadian organization in the lizardSceloporus occidentalis: The effects of pinealectomy, blinding, and melatonin

Abstract: Pinealectomy of the iguanid lizardSceloporus occidentalis freerunning in either continuous illumination or continuous darkness typically causes changes in the period of the activity rhythm as well as changes in the amount of daily activity (α). Blinding also alters the period of the freerunning activity rhythm. Continuous long term administration of melatonin via subcutaneous capsules causes a significant lengthening of the period of the activity rhythm (as well as a decrease in α) of pinealectomized and/or blinded lizards showing that melatonin exerts its action at extrapineal and extraocular sites. However, the amount of lengthening induced by melatonin is significantly greater in pinealectomized lizards than in intact lizards. The results indicate that the pineal (and possibly the eyes) act as coupling devices or as the loci of circadian pacemakers within a multioscillator system. Melatonin may function as a chemical messenger between the pineal (or eyes) and the rest of the circadian system.

Melatonin Production by Extra-pineal Tissues

Abstract: Hydroxyindole-O-methyltransferase (HIOMT), which catalyzes the O-methylation of N-acetylserotonin to melatonin, is not confined to pineal glands, as was thought when the enzyme was first described in 1960. Five years later it was noted that HIOMT is present in the brain and eyes of anuran amphibians, fishes, reptiles and birds. Indeed, in anurans, HIOMT in the retina has far greater activity than in the pineal body. Whereas HIOMT can be detected in the retina of fetal rats, not until a few days after birth can it be demonstrated in the pineal gland. In the mole there is two to ten times more HIOMT activity in the eyes than in the pineal gland. The HIOMT in the retina and pineal gland appear to have similar properties. There is also an HIOMT in the Harderian glands of rats, but it has biochemical characteristics that differ from retinal and pineal HIOMT. N-Acetyltransferase (NAT), which converts serotonin to N-acetylserotonin is found not only in the pineal gland but also in the retina of chickens, sparrows and rats. Furthermore, NAT activity varies diurnally like the enzyme of the pineal gland, being higher during the dark phase than during light. Melatonin has been localized by bioassay and immunohistochemical technique to several regions of the brain and the retina of chickens and rats, the retina of trout, the Harderian gland of rats, and the gut of humans, rats and rabbits. The evidence is quite convincing that all these organs synthesize melatonin and do not acquire it totally from the pineal gland via the blood. Indeed, following pinealectomy, melatonin can still be detected in the serum of rats. Melatonin is also present in the brain of rats, the eyes of chickens and trout, and in the blood of trout, mice and sheep after the pineal gland has been ablated. It is evident that melatonin is not a unique or exclusive product of pineal glands. Melatonin is synthesized by and released from a number of tissues. It seems possible that the cells which produce melatonin are within the widely-dispersed APUD system.

The effect of pinealectomy on seasonal changes in prolactin secretion in the white-tailed deer (Odocoileus virginianus borealis).

Abstract: Surgery was performed on four buck and four doe 9-month-old white-tailed deer in March of 1978. Pinealectomy was performed on two deer of each sex, and the remaining animals received sham operations. At monthly intervals over the following year, baseline and TRH-stimulated (200 μg/deer; iv bolus) serum PRL was measured over a 3-h period by RIA. Baseline PRL levels in sham-operated animals followed a circannual pattern, with peak levels occurring in June (74–237 ng/ml for does; 34–193 ng/ml for bucks) and lowest levels occurring in midwinter (0.41–0.44 ng/ml for does; 0.10–0.13 ng/ml for bucks). Pituitary responsivity to TRH followed the same pattern as that seen for basal PRL levels in sham-operated deer, with the highest peak serum PRL responses in June (198–568 ng/ml for does; 190–395 ng/ml for bucks) and the lowest peaks seen in midwinter (0.27–0.80 ng/ml for does; 0.29–2.62 ng/ml for bucks) Pinealectomy appeared to abolish the circannual basal serum PRL rhythms in bucks, while this rhythm was maintain...

The effect of pinealectomy, continuous light, and continuous darkness on metamorphosis of anadromous sea lampreys, Petromyzon marinus L.

Abstract: The role of the pineal complex in lamprey metamorphosis was investigated by examining the influence of pinealectomy and continuous light and darkness on the initiation of this event in anadromous sea lampreys, Petromyzon marinus L. Larval lampreys, which on the basis of a condition factor were considered likely to enter metamorphosis in July, were separated in May of 1979 and 1980 into the following groups: (1) intact controls, (2) sham-operated controls, (3) pinealectomized individuals, (4) those exposed to continuous light, and (5) those exposed to continuous light or dark. The importance of the pineal complex to metamorphosis was supported by morphological evidence that, in all presumably pinealectomized individuals that entered metamorphosis, the complex had apparently not been removed during the surgical procedure. The ways in which the pineal complex may be involved in lamprey metamorphosis are discussed.

Effects of pinealectomy and melatonin on the photoperiodic gonadal response of the male lizard Anolis carolinensis

Abstract: The effects of pinealectomy and exogenous melatonin treatment on the photoperiodic testicular response in the lizard Anolis carolinensis were examined at two times of year. In the summer (July–August) neither pinealectomy nor melatonin affected the photoperiodic response. In the fall (September–October) pinealectomy had a progonadal effect in lizards maintained on either LD 8:16 or LD 14:10 photoperiods. Melatonin blocked the gonadal development in response to pinealectomy on LD 8:16 but melatonin did not inhibit the acceleration in testicular development caused by pinealectomy on LD 14:10. However, melatonin did inhibit testicular development in intact (nonpinealectomized) anoles exposed to LD 14:10. These results show that pinealectomy can modify testicular function in Anolis, that the effects of pinealectomy are seasonal, and that melatonin may be a reproductively active factor involved.

Effects of growing tumours on pineal melatonin levels in male rats.

Abstract: The effect of transplantable tumours (Yoshida Sarcoma) on pineal melatonin content was studied in Wistar rats. A negative correlation between pineal melatonin content and size of growing tumours was observed. Effects of chronic treatment with drugs interfering with n=melatonin or serotonin biosynthesis on tumour growth as well as the influence of tumour growth on pineal melatonin content were investigated. Tumour growth enhancement observed after administration of some substances producing a decrease of pineal melatonin is discussed. Pinealectomy stimulates malignant growth. This may be caused by lack of endogenous melatonin.

Melatonin and Pigment Cell Rhythmicity

Abstract: The synthesis of melatonin is a very regular and reliable nocturnal event, which may provide a template, to other physiological systems, of the scotophase length. Such a melatonin template has been hypothesized to provide timing information for the maintenance entrained daily, circadian and circannual cycles. The action of melatonin in cueing these rhythmic phenomena may either directly or indirectly influence various biological rhythms. The evidence concerning melatonin's direct involvement in entraining melanosome migration cycles in the dermal melanophores of fishes and within the vertebrate retinal pigmented-epithelium is reviewed. The state of melanosome dispersal or aggregation in the dermal melanophore of fishes may be under oMSH control from the pituitary gland, may be under neural control, may be affected by melatonin, or any combination of these three depending upon the species being examined. Melatonin does not affect the dermal melanophores in all fishes. The available data suggests that melatonin's affect on fish coloration is more pronounced in larval and juvenile fishes with the affect either disappearing, or being masked in adult animals. In those fishes which are sensitive to melatonin, a pallor is noted at night, with pinealectomy abolishing the nightlypallor rhythm. Circulating melatonin undergoes an increase in titer at night when compared to day time values in the trout. It is therefore possible that circulating melatonin may directly induce nightly palloring in larval trout. Evidence is reviewed which suggests that circulating melatonin is not involved in the maintenance of body coloration in adult trout nor is it involved in background coloration adaptation. The melanosomes within the retinal pigmented-epithelium undergo daily cycles of aggregation and dispersion in many vertebrates. Melatonin has been shown to affect the aggregation of melanosomes in both the trout and guinea pig pigmented-epithelium. Pinealectomy alters the state of pigment aggregation within the trout pigmented-epithelium. Evidence is reviewed concerning whether retinal or pineal gland melatonin is involved in the retinal melanosome aggregation-dispersion cycle. Finally data which demonstrates the presence of a melatonin-binding protein within the ocular tissue is presented and discussed.

Role of the sympathetic nervous system in the control of the goitrogenic response in the rat.

Abstract: The role of the sympathetic nervous system in the control of the goitrogenic response was examined in adult male rats subjected to superior cervical ganglionectomy (SCGx) 7 days earlier. In the first experiment, superior cervical ganglionectomized (SCGx) or sham-operated animals were treated with the goitrogenic agent methylmercaptoimidazole (MMI) for 4 days, and their thyroid weights and plasma TSH levels were measured. After MMI administration, the increase in thyroid weight was significantly greater in SCGx than in sham-operated rats. The plasma TSH increases after MMI were similar in both groups. To rule out the possible involvement of the pineal gland, MMI treatment was carried out in rats subjected to pinealectomy or sham pinealectomy 7 days earlier. Thyroid weights and plasma TSH levels after pinealectomy were not different from controls in vehicle- or MMI-treated rats. In a third experiment, the goitrogenic response to TSH was assessed in SCGx or shamoperated rats; the thyroid weight of SCGx anima...

The effect of superficial pinealectomy on reproduction and brown fat in the adult white-footed mouse,Peromyscus leucopus

Abstract: A method for superficial pinealectomy of the adult white-footed mouse,Peromyscus leucopus, is presented. Histological examination of the brain of pinealectomized mice showed that the deep pineal gland was left intact. The survival rate of pinealectomized mice was 80%. Pinealectomized mice were exposed to a short day photoperiod (8L:16D) at 15°C for 7 weeks. After this time male mice maintained active gonads with a testicular index (TI, testis width×length/body weight) of 2.0±0.1. Testis weight was 202±35 mg, and the seminiferous tubules contained abundant spermatozoa (spermatogenic index [SI]=4.5±0.2). Sham operated animals had regressed testes. TI was 1.2±0.2, testis weight was 97±26 mg, and the SI was 2.7±0.7 (allP<0.05 relative to pinealectomized mice). Pinealectomized females were reproductively competent in that all of the mice had a perforate vagina, the reproductive tract weight (vagina, uterus, oviducts, and ovaries) was 111±15 mg, and the ovaries from each animal contained preovulatory follicles. Sham operated mice had an imperforate vagina, reproductive tract weights were 34±5 mg, and in only 1 out of 5 mice did the ovaries contain a preovulatory follicle (allP<0.05). The weight of the lipid-free interscapular brown fat was 28% less in pinealectomized mice relative to sham operated animals (P<0.01). These results support the role of the pineal gland as regulator of short day, cold induced reproductive regression and brown fat hypertrophy.

Molecular Endocrinology of Melatonin: Receptor Sites in Brain and Peripheral Organs

Abstract: This paper reviews the data indicating the occurrence of membrane and cytoplasmic melatonin binding sites in selected brain areas, e.g . medial basal hypothalamus and pineal gland, and in peripheral organs like the uterus, ovary and liver. Evidence is also presented that the neuroendocrine responsiveness to melatonin in a number of situations (diurnal cycle, continuous exposure to light, pinealectomy, superior cervical ganglionectomy, underfeeding) correlates with the number of membrane melatonin sites in rat and hamster brains.

Role of the Pineal Gland in Male Rats Chronically Exposed to Increased Temperature

Abstract: The effects of the pineal gland on endocrine function (especially those of the gonads) were investigated in male rats chronically exposed to increased temperature. Weanling male rats were either pinealectomized (Px) or sham-operated (Sh). Following one week of recovery, animals were assigned to either control temperature of 21±1°C (PxC and ShC) or a temperature of 35±1°C (PxH and ShH). The animals were kept at their respective temperature for at least 30 days. In both groups (PxH and ShH) exposure to increased temperature resulted in a significant reduction in body and hypophysial weights, and in serum LH and testosterone levels as compared with the respective controls (PxC and ShC). Rectal temperature and serum corticosterone were also significantly increased. No changes were found in pineal hydroxyindole-O-methyltransferase activity of shamoperated rats kept in increased temperature (ShH vs. ShC). Pinealectomy alone (PxC vs. ShC) did not alter any of the measured parameters, except for increased pituitary LH content. Increased temperature plus pinealectomy (PxH vs. PxC; and PxH vs. ShH) caused a significant reduction in pituitary LH content and further accentuated (PxH vs. ShH) the diminished serum LH and testosterone levels evoked by exposure to high temperature. The results suggest that in male rats the pineal gland may play a role in moderating the changes in the reproductive processes that are induced by increased temperature.

Changes in drinking behavior caused by superior cervical ganglionectomy and pinealectomy in rats.

Abstract: The effect of superior cervical ganglionectomy (SCGx) or pinealectomy (Px) on drinking behavior was examined in rats subjected to a restricted photoperiod (i.e. 4 h of light per day). Both in male and female rats SCGx depressed water intake significantly from 1 to 3 days after surgery. After osmolar (i.p. 5% NaCl) or non-osmolar stimuli (s.c. isoproterenol) SCGx female rats exhibited a depressed response in water and NaCl intake, an effect not observed in male rats. Castration of male or female rats did not change their drinking behavior response to thirst stimuli. Px did not mimic SCGx in its effects on drinking behavior; moreover in sham-Px rats the water intake fell significantly after craniotomy. Following the injection of isoproterenol or i.p. hypertonic saline, the drinking behavior was the same in Px or sham-Px animals. To assess whether the effects of SCGx needed the presence of the pineal gland, Px or sham-Px rats were subjected to SCGx 9 days later. In both groups SCGx depressed water intake; however the inhibition that followed ganglia removal in Px rats was greater than that observed in animals with a pineal gland. Water and NaCl intake following isoproterenol or i.p. hypertonic saline were similar in both experimental groups. These results suggest that SCGx affects drinking behavior in part by pathways other than pineal denervation.

Nutritional Status, Time of Day and Pinealectomy: Factors Influencing the Sensitivity of the Neuroendocrine-Reproductive Axis of the Rat to Melatonin

Abstract: Afternoon but not morning injections of melatonin (Mel) resulted in significant 68, 50 and 20% reductions in seminal vesicle, ventral prostate and testicular weights, respectively, as compared with underfed controls. As in the animals injected in the morning, reproductive organ weights in underfed-pinealectomized rats were unaffected by afternoon injections of Mel. Both pituitary and serum prolactin levels were significantly depressed in underfed rats receiving Mel in the afternoon; however, Mel was ineffective when given either in the morning or to pinealectomized rats. These data indicate that there is a diurnal rhythm of sensitivity to Mel in undernourished rats which is abolished by pinealectomy.

Role of the serotoninergic neuron system of the brain stem on the release of thyrotrophic and luteinizing hormone.

Abstract: 1. Decrease of brain serotonin concentration, elicited by either parachlorophenylalanine treatment, surgical interruption of the ascending serotoninergic fibres, or by pinealectomy provokes an enhanced release both of TSH and LH. 2. Increased serotonin content of the brain, produced by intraventricular, intrahypothalamic or systemic administration of serotonin, results in a significant inhibition of the release of these two trophic hormones. 3. It is concluded that the serotoninergic neuron system of the brain stem represents an inhibitory mechanism in the neuroendocrine circuit regulating pituitary trophic hormone release.

Structural changes in the pars intermedia of the cichlid teleost Sarotherodon mossambicus as a result of background and adaptation and illumination. III. The role of the pineal organ.

Abstract: The MSH producing cells in the pars intermedia of Sarotherodon mossambicus have been shown to be involved in background adaptation processes. Reflected light received by the eyes affects the activity of these cells. In the present study the hypothesis has been tested that also the pineal organ, as a second photoreceptor, is involved in regulation of the metabolic activity of the MSH cells. The pineal organ appears to contain photoreceptor cells and is considered to be capable of transferring information about light conditions to the animal. Removal of the pineal organ of fish kept on a black background has no effect on activity of MSH cells, whereas the activity of these cells in fish kept in darkness is increased. Thus it seems that the pineal organ exercises its influence on MSH cells only in darkness and that this influence results in a reduced activity of these cells. It is therefore concluded that the metabolic activity of MSH cells is inhibited not only by reflected light received by the eyes, but also by the action of the pineal organ as a result of the absence of illumination. No structural signs of secretory activity can be observed in the pineal, which might indicate synthesis or release of substances like melatonin. However, administration of melatonin reduces the activity of MSH cells. Neither pinealectomy nor treatment with melatonin has any influence on the second cell type of the pars intermedia, the PAS positive cells.