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Pineal Gland Abstracts: 2001
Note: the following is a limited selection of abstracts available at PubMed, Science Direct, and Toxnet.
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Caries Res 2001 Mar-Apr;35(2):125-8
Fluoride deposition in the aged human pineal gland.
Luke J.
School of Biological Sciences, University of Surrey, Guildford, UK. jenniluke@compuserve.com
The purpose was to discover whether fluoride (F) accumulates in the aged human pineal gland. The aims were to determine (a) F-concentrations of the pineal gland (wet), corresponding muscle (wet) and bone (ash); (b) calcium-concentration of the pineal. Pineal, muscle and bone were dissected from 11 aged cadavers and assayed for F using the HMDS-facilitated diffusion, F-ion-specific electrode method. Pineal calcium was determined using atomic absorption spectroscopy. Pineal and muscle contained 297+/-257 and 0.5+/-0.4 mg F/kg wet weight, respectively; bone contained 2,037+/-1,095 mg F/kg ash weight. The pineal contained 16,000+/-11,070 mg Ca/kg wet weight. There was a positive correlation between pineal F and pineal Ca (r = 0.73, p<0.02) but no correlation between pineal F and bone F. By old age, the pineal gland has readily accumulated F and its F/Ca ratio is higher than bone.
PMID: 11275672 [PubMed - indexed for MEDLINE]
Eur J Histochem 2001;45(2):141-50
Lactate dehydrogenase activity of rat epididymis and spermatozoa: effect of constant light.
Ponc RH, Carriazo CS, Vermouth NT.
Facultad de Odontologia, Uni- versidad Nacional de Cordoba, Argentina.
During its passage through the epididymis, the gamete undergoes a process of "maturation" leading to the acquisition of its fertilizing ability. The epididymis displays regional variations in the morphology and metabolic properties of its epithelium which are relevant for the progressive development of mature sperm characteristics. The epididymis has spontaneous peristaltic contractions and receives sympathetic innervation that is modulated by melatonin, a hormone synthesized and released by the pineal gland. Constant lighting disrupts melatonin synthesis and secretion. We have studied the effect of constant light on lactate dehydrogenase (LDH; EC 1.1.1.27) and its isozyme C4 activities and protein content in whole epididymis, epididymal tissue and in spermatozoa from caput and cauda segments. Animals were exposed from birth to an illumination schedule of 14 h light:10 h dark (group L:D). At 60 days of age one group of animals was submitted to constant light over 50 days (group L:L). In order to test the fertilizing ability, the rats of each group were mated with soliciting estrous females. The percentage of pregnancies in females mated with males maintained in L:L was remarkably lower than those in females mated with males maintained in the L:D photoperiod (44% and 88% respectively). Constant light increased protein concentration and LDH activity in caput as well as in cauda of total epididymis. On the contrary, in epididymal tissue, the protein content decreased in both epididymal sections compared with controls. When enzymatic activity was expressed in Units per spermatozoa, constant light induced a significant reduction of total LDH and LDHC4 in caput and cauda spermatozoa while LDH activity of epididymal tissue was not affected. In spite of the decrease in LDH per sperm cell when rats were exposed to constant light, in total epididymis (epididymis tissue plus sperm cells content) and in spermatozoa, values of enzyme activities expressed per weight unit were higher than those of controls. This is explained by the increase in the amount of stored spermatozoa, both in caput and cauda, produced by exposure of animals to constant light. Our results confirm that in rats, chronic exposure to constant light promotes a reduction of fertilizing ability and indicates that continuous lighting reduces the total LDH and LDHC4 activities, possibly due to moderate aging of spermatozoa within the duct by lengthening of the sperm transit through the epididymis.
PMID: 11512635 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11703567&dopt=AbstractJ Pineal Res 2001 Nov;31(4):363-9
Melatonin modulates allergic lung inflammation.
Martins E Jr, Ligeiro de Oliveira AP, Fialho de Araujo AM, Tavares de Lima W, Cipolla-Neto J, Costa Rosa LF.
Department of Physiology and Biophysics, the Institute of Biomedical Sciences, University of Sao Paulo, Av. Prof. Lineu Prestes 1524, 05508-900, Sao Paulo, SP, Brazil.
Asthma is an inflammatory lung disease characterized by cell migration, bronchoconstriction and hyperresponsiveness, and can be induced, as an experimental model, by ovalbumin sensitization followed by a challenge. In addition to the well-known immunostimulatory effects of melatonin, research has identified some of its anti-inflammatory properties. In this study, we evaluated the influence of pinealectomy and melatonin administration on cell migration in an experimental model of allergic airway inflammation. We evaluated, in pinealectomized rats treated or not with melatonin, cell migration into the bronchoalveolar fluid, the number of cells and their proliferative activity in the bone marrow, and plasma corticosterone levels. Pinealectomy reduces, 24 hr after the challenge, the total cell number count in the lung and bone marrow cell proliferation, without changing the number of cells in the bone marrow or in the peripheral blood. This fact suggests that melatonin is important in the control of cell recruitment from the bone marrow and the migration of those cells to the lung. Melatonin administration to pinealectomized rats seems to restore the ability of cells to migrate from the bone marrow to the bronchoalveolar fluid. So, the development of specific inhibitors of melatonin would benefit patients with asthma.
PMID: 11703567 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11604480&dopt=AbstractJ Natl Cancer Inst 2001 Oct 17;93(20):1563-8
Comment in:
- J Natl Cancer Inst. 2001 Oct 17;93(20):1513-5.
- J Natl Cancer Inst. 2002 Apr 3;94(7):530; discussion 532-3.
- J Natl Cancer Inst. 2002 Apr 3;94(7):531-2; discussion 533-4.
Rotating night shifts and risk of breast cancer in women participating in the nurses' health study.
Schernhammer ES, Laden F, Speizer FE, Willett WC, Hunter DJ, Kawachi I, Colditz GA.
E. S. Schernhammer, Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA. eva.schernhammer@channing.harvard.edu
BACKGROUND: Melatonin shows potential oncostatic action, and light exposure during night suppresses melatonin production. There is little information, however, about the direct effect of night work on the risk of cancer. We investigated the effect of night work in breast cancer.
METHODS: We examined the relationship between breast cancer and working on rotating night shifts during 10 years of follow-up in 78 562 women from the Nurses' Health Study. Information was ascertained in 1988 about the total number of years during which the nurses had worked rotating night shifts with at least three nights per month. From June 1988 through May 1998, we documented 2441 incident breast cancer cases. Logistic regression models were used to calculate relative risks (RRs) and 95% confidence intervals (CIs), adjusted for confounding variables and breast cancer risk factors. All statistical tests were two-sided.
RESULTS: We observed a moderate increase in breast cancer risk among the women who worked 1-14 years or 15-29 years on rotating night shifts (multivariate adjusted RR = 1.08 [95% CI = 0.99 to 1.18] and RR = 1.08 [95% CI = 0.90 to 1.30], respectively). The risk was further increased among women who worked 30 or more years on the night shift (RR = 1.36; 95% CI = 1.04 to 1.78). The test for trend was statistically significant (P =.02).
CONCLUSIONS: Women who work on rotating night shifts with at least three nights per month, in addition to days and evenings in that month, appear to have a moderately increased risk of breast cancer after extended periods of working rotating night shifts.
PMID: 11604480 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11568714&dopt=AbstractSpine 2001 Sep 1;26(17):E385-91
Pathologic mechanism of experimental scoliosis in pinealectomized chickens.
Machida M, Dubousset J, Satoh T, Murai I, Wood KB, Yamada T, Ryu J.
Department of Orthopaedic Surgery and Biochemistry, Nihon University School of Medicine, Tokyo, Japan.
STUDY DESIGN: This study was designed to investigate the pathologic mechanisms of idiopathic scoliosis using experimentally induced scoliosis in chickens. OBJECTIVE: To understand the process of producing a scoliotic deformity in pinealectomized chickens.
SUMMARY OF BACKGROUND DATA: Pinealectomy in chickens consistently produces scoliosis with anatomic characteristics similar to those of human idiopathic scoliosis. Pinealectomized chickens are an important animal model for the study of idiopathic scoliosis. METHODS: In this study, 40 chickens were divided into two groups; 20 chickens treated with pinealectomy and 20 with a sham operation as control subjects on the second after hatching. The chickens in both groups then were killed at intervals ranging from 1 to 20 weeks after surgery. Their spines were examined visually and radiologically for the presence of a scoliotic curve and vertebral deformities.RESULTS: Rotational lordoscoliosis developed in pinealectomized chickens. The chickens with severe scoliosis were characterized by apically wedge-shaped vertebrae. In contrast, no scoliosis with any vertebral deformity developed in any of the chickens that received a sham operation.
CONCLUSIONS: Because there normally is evidence of lordosis in the thoracic spine of chickens, the rotational instability of the spine induced by pinealectomy may produce a scoliotic deformity as a secondary phenomenon. Pinealectomy in chickens consistently produces scoliosis with anatomic characteristics similar to those of human idiopathic scoliosis. The authors believe that disturbance of the equilibrium and the posture mechanism associated with a defect in melatonin synthesis after pinealectomy may promote the development of rotational lordoscoliosis.
PMID: 11568714 [PubMed - indexed for MEDLINE]Note from FAN: Definitions
Lordosis - 1. a normal anteriorly convex curvature of the vertebral column. 2. an abnormal anteriorly convex curvature of the spine, usually lumbar. [G. lordosis, a bending backward]
Lordoscoliosis: combined backward and lateral curvature of the spine . [G. lordos, bent back, + skoliosis, crookedness, fr. skolios, bent, aslant]
Ref: Stedman's Concise Medical Dictionary for the Health Professions. 2001.. Illustrated 4th Edition. Ed. John H. Dirckx, MD. Lippincott Williams & Wilkins, Baltimore, Maryland.
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11568714&dopt=AbstractSpine 2001 Sep 1;26(17):E385-91
Pathologic mechanism of experimental scoliosis in pinealectomized chickens.
Machida M, Dubousset J, Satoh T, Murai I, Wood KB, Yamada T, Ryu J.
Department of Orthopaedic Surgery and Biochemistry, Nihon University School of Medicine, Tokyo, Japan.
STUDY DESIGN: This study was designed to investigate the pathologic mechanisms of idiopathic scoliosis using experimentally induced scoliosis in chickens.
OBJECTIVE: To understand the process of producing a scoliotic deformity in pinealectomized chickens.
SUMMARY OF BACKGROUND DATA: Pinealectomy in chickens consistently produces scoliosis with anatomic characteristics similar to those of human idiopathic scoliosis. Pinealectomized chickens are an important animal model for the study of idiopathic scoliosis.
METHODS: In this study, 40 chickens were divided into two groups; 20 chickens treated with pinealectomy and 20 with a sham operation as control subjects on the second after hatching. The chickens in both groups then were killed at intervals ranging from 1 to 20 weeks after surgery. Their spines were examined visually and radiologically for the presence of a scoliotic curve and vertebral deformities. RESULTS: Rotational lordoscoliosis developed in pinealectomized chickens. The chickens with severe scoliosis were characterized by apically wedge-shaped vertebrae. In contrast, no scoliosis with any vertebral deformity developed in any of the chickens that received a sham operation.
CONCLUSIONS: Because there normally is evidence of lordosis in the thoracic spine of chickens, the rotational instability of the spine induced by pinealectomy may produce a scoliotic deformity as a secondary phenomenon. Pinealectomy in chickens consistently produces scoliosis with anatomic characteristics similar to those of human idiopathic scoliosis. The authors believe that disturbance of the equilibrium and the posture mechanism associated with a defect in melatonin synthesis after pinealectomy may promote the development of rotational lordoscoliosis.
PMID: 11568714 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11519977&dopt=AbstractActa Paediatr 2001 Jul;90(7):751-6
Precocious puberty in children with tumours of the suprasellar and pineal areas: organic central precocious puberty.
Rivarola, Belgorosky A, Mendilaharzu H, Vidal G.
Endocrinology Service, Hospital de Pediatria Garrahan, Buenos Aires, Argentina. mariv@elsitio.net
During the past 11 y, 115 children younger than 8/9 y of age (female/male) with tumours of the suprasellar or pineal areas were followed in our clinic to study the incidence of precocious puberty. In addition, type of central lesion, clinical characteristics and gonadotropic secretion were studied in order to elucidate the different mechanisms of gonadal activation. A control group of 21 patients with idiopathic precocious puberty and a control group of 10 age-matched patients with suprasellar tumours without precocious puberty were also studied. Precocious puberty associated with organic central lesions was found at diagnosis in 30 patients (26%), in 9 out of 48 patients with glial cell tumours (18.7%), 6 out of 9 patients with germ cell tumours (66.6%), 11 out of 11 patients with hypothalamic hamartomas (100%) and in 4 out of 4 patients with subarachnoid cysts or arachnoidocele (100%). Precocious puberty was not found in any of 36 patients with craniopharyngioma. With the exception of one patient with pineal germinoma, all lesions were localized to the suprasellar area. In all patients with hypothalamic hamartoma, precocious puberty was diagnosed before 4 y of age, while in most patients with the other lesions, it was diagnosed after this age. Height SDS, weight increase and advancement of bone age were similar in both idiopathic and organic central precocious puberty. Maximal LH responses to GnRH in idiopathic and organic central precocious puberty were similar except for germ cell tumours. Patients with suprasellar tumours without precocious puberty had lower maximal LH (but not FSH) responses to GnRH, with the exception of germ cell tumours. In the latter, elevation of serum beta-hCG indicates that this gonadotropin was responsible for gonadal stimulation. In hypothalamic hamartomas, the prepubertal hiatus in the activity of the GnRH pulse generator was absent. The mechanism of this failure in the inactivation of GnRH is unknown. Data suggest that in glial cell tumours and in subarachnoid cysts, an unknown factor, probably secreted by the tumours, advances the tempo of GnRH maturation. Therefore, the aetiology of organic central precocious puberty is multiple and is directly related to location and type of lesion.
CONCLUSION: This clinical information suggests that the onset of puberty is not the result of the disruption of a putative pulse generator inhibitory influence but the consequence of secretion of stimulatory substances by the lesions.
PMID: 11519977 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11490097&dopt=AbstractBiol Signals Recept 2001 Sep-Oct;10(5):317-25
Maternal transfer of melatonin alters the growth and sexual maturation of young Indian palm squirrel Funambulus pennanti.
Bishnupuri KS, Haldar C.
Department of Zoology, Banaras Hindu University, Varanasi, India.
To date, the phenomenon of maternal transfer of hormones to the young is an enigma. The present study explains for the first time the maternal transfer of melatonin (MEL) to the young, affecting neonatal growth and sexual maturation. The suckling pups of MEL-treated mothers exhibited significant decreases in body, testicular, vas deferens (male pups), ovarian and uterine (female pups) weights and increases in pineal gland activity along with high plasma MEL levels. The plasma level of testosterone decreased significantly in male pups, while estradiol increased and progesterone decreased in female pups of MEL-treated mothers. These results clearly suggest that MEL could be transported from the mothers to their young postnatally via the milk in order to influence neonatal growth and sexual maturation. Our results support the earlier concept and show for the first time that MEL can be transported from the mother to the young either prenatally through the placenta or postnatally via the milk. Therefore, maternal MEL can act as a biological signal for neonatal growth and sexual maturation. Copyright 2001 S. Karger AG, Basel
PMID: 11490097 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11168908&dopt=AbstractJ Pineal Res 2001 Jan;30(1):56-64
A test of the coincidence and duration models of melatonin action in Siberian hamsters. II. The effects of 4- and 8-hr melatonin infusions on testicular development of pinealectomized juvenile Siberian hamsters (Phodopus sungorus).
Gunduz B, Stetson MH.
Department of Biological Sciences, University of Delaware, Newark 19716, USA.
In a previous paper we demonstrated that properly timed 1-hr infusions of 50 ng melatonin effectively suppressed testicular development in juvenile Siberian hamsters. Only melatonin infused between 20:00 and 21:00 hr was effective in animals exposed to 16L (lights off 20:00 hr). In this paper we further investigate the importance of the coincidence and duration hypotheses of daily exposure of melatonin. Prepubertal Siberian hamsters received either 4- or 8-hr melatonin infusions at various times either on long photoperiod (LD 16:8 = 16L) or on short photoperiod (LD 10:14 = 10L). Daily 8-hr melatonin infusions suppressed testicular development in both photoperiods. Daily 4-hr, 50 ng/hr, melatonin infusions at 17:00-21:00 hr inhibited testicular growth in 16L and daily 4-hr melatonin infusions (either 50 ng/h or 50 ng/day) inhibited testicular growth at 17:00-21:00 hr in 10L. We also tested the efficacy of an interrupted melatonin infusion of long duration (8 hr). Pinealectomized prepubertal male Siberian hamsters, born on 16L, were infused with two signals of 4 hr separated by an interval of 2 hr. Melatonin-infused groups had significantly inhibited testicular growth compared to vehicle-infused animals. Testicular development was maximally inhibited only in those groups in which the period of melatonin sensitivity identified in the previous paper (20:00-21:00 hr) overlapped or immediately followed a period of melatonin infusion. Considering the restrictions of the experimental design employed in these studies, the results are best explained by the hypothesis that the photoperiodic gonadal response in juvenile Siberian hamsters is regulated by the coincidence in time of exogenously administered melatonin with an intrinsic rhythm of sensitivity to melatonin, which occurred at 20:00-21:00 hr. The duration of the melatonin signal alone can not explain the results.
PMID: 11168908 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11226744&dopt=AbstractExp Gerontol 2001 Feb;36(2):297-310
Effects of melatonin in perimenopausal and menopausal women: a randomized and placebo controlled study.
Bellipanni G, Bianchi P, Pierpaoli W, Bulian D, Ilyia E.
Menopause Center, Madonna delle Grazie Health Institute, Velletri, Rome, Italy.
In aging humans, night levels of melatonin (MEL) decline progressively. Also thyroid and gonadal functions decline during aging while gonadotropins (luteotropic hormone (LH) and follicle stimulating hormone (FSH)) steadily increase. A desynchronization of pineal circadian cyclicity as expressed by the progressive decrease of the MEL night peak may be permissively linked to the onset and progression of menopause. We studied the effects of exogenous, evening administration of MEL on the level of hormones which are known to be involved in the genesis and progression of menopause. Perimenopausal and menopausal women from 42 to 62years of age with no pathology or medication were selected. MEL was measured in saliva to divide them into low, medium and high-MEL patients. Half of them took 3mg MEL and half of them Placebo at bedtime (10-12p.m.) in a fully randomized and double-blind fashion. Three and six months later blood was taken for determination of pituitary (LH, FSH), ovarian, and thyroid hormones I(T3 and T4). All women taking MEL with low basal level of MEL and/or Placebo for three and six months showed a significant increase in levels of thyroid hormones. Before initiation of the study, a negative correlation was found in all women between LH, FSH and basal MEL levels. Within six months of treatment, MEL produced a significant diminution of LH in the younger women (43 to 49year-old), while no effect was seen in the older women (50-62years old). A decrement of FSH was observed in MEL-treated women with low basal MEL levels. In addition, most MEL-treated women reported a general improvement of mood and a significant mitigation of depression. MEL decline during aging may thus signal the derangement of pineal and pituitary-controlled ovarian cyclicity and the progressive quenching of fertility in women. These findings seem to show a recovery of pituitary and thyroid functions in MEL-treated women, towards a more juvenile pattern of regulation.
Publication Types:
- Clinical Trial
- Randomized Controlled Trial
PMID: 11226744 [PubMed - indexed for MEDLINE]
Full free report available at http://www.jbc.org/cgi/content/full/276/46/43400J Biol Chem 2001 Nov 16;276(46):43400-6
Differentiation-associated Na+-dependent inorganic phosphate cotransporter (DNPI) is a vesicular glutamate transporter in endocrine glutamatergic systems.
Hayashi M, Otsuka M, Morimoto R, Hirota S, Yatsushiro S, Takeda J, Yamamoto A, Moriyama Y.
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Okayama University, Okayama 700-8530, Japan.
Vesicular glutamate transporter is present in neuronal synaptic vesicles and endocrine synaptic-like microvesicles and is responsible for vesicular storage of L-glutamate. A brain-specific Na(+)-dependent inorganic phosphate transporter (BNPI) functions as a vesicular glutamate transporter in synaptic vesicles, and the expression of this BNPI defines the glutamatergic phenotype in the central nervous system (Bellocchio, E. E., Reimer, R. J., Fremeau, R. T., Jr., and Edwards, R. H. (2000) Science 289, 957-960; Takamori, S., Rhee, J. S., Rosenmund, C., and Jahn, R. (2000) Nature 407, 189-194). However, since not all glutamatergic neurons contain BNPI, an additional transporter(s) responsible for vesicular glutamate uptake has been postulated. Here we report that differentiation-associated Na(+)-dependent inorganic phosphate cotransporter (DNPI), an isoform of BNPI (Aihara, Y., Mashima, H., Onda, H., Hisano, S., Kasuya, H., Hori, T., Yamada, S., Tomura, H., Yamada, Y., Inoue, I., Kojima, I., and Takeda, J. (2000) J. Neurochem. 74, 2622-2625), also transports L-glutamate at the expense of an electrochemical gradient of protons established by the vacuolar proton pump when expressed in COS7 cells. Molecular, biological, and immunohistochemical studies have indicated that besides its presence in neuronal cells DNPI is preferentially expressed in mammalian pinealocytes, alphaTC6 cells, clonal pancreatic alpha cells, and alpha cells of Langerhans islets, these cells being proven to secrete L-glutamate through Ca(2+)-dependent regulated exocytosis followed by its vesicular storage. Pancreatic polypeptide-secreting F cells of Langerhans islets also expressed DNPI. These results constitute evidence that DNPI functions as another vesicular transporter in glutamatergic endocrine cells as well as in neurons.
PMID: 11551935 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11488943&dopt=AbstractEur J Neurosci 2001 Jul;14(1):1-9
Analysis of cell signalling in the rodent pineal gland deciphers regulators of dynamic transcription in neural/endocrine cells.
Stehle JH, von Gall C, Korf HW.
Dr Senckenbergische Anatomie, Anatomisches Institut II, Hs 26, Johann Wolfgang Goethe-Universitat Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany. stehle@em.uni-frankfurt.de
In neurons, a temporally restricted expression of cAMP-inducible genes is part of many developmental and adaptive processes. To understand such dynamics, the neuroendocrine rodent pineal gland provides an excellent model system as it has a clearly defined input, the neurotransmitter norepinephrine, and a measurable output, the hormone melatonin. In this system, a regulatory scenario has been deciphered, wherein cAMP-inducible genes are rapidly activated via the transcription factor phosphoCREB to induce transcriptional events necessary for an increase in hormone synthesis. However, among the activated genes is also the inhibitory transcription factor ICER. The increasing amount in ICER protein leads ultimately to the termination of mRNA accumulation of cAMP-inducible genes, including the gene for the Aa-nat that controls melatonin production. This shift in ratio of phosphoCREB and ICER levels that depends on the duration of stimulation can be interpreted as a self-restriction of cellular responses in neurons and has also been demonstrated to interfere with cellular plasticity in many non-neuronal systems.
Publication Types:Review
Review, Tutorial
PMID: 11488943 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11514903&dopt=AbstractBraz J Biol 2001 May;61(2):333-40
Influence of the pineal gland on the physiology, morphometry and morphology of pancreatic islets in rats.
de Lima LM, dos Reis LC, de Lima MA.
Universidade de Uberaba. lima@mednet.com.br
To investigate the influence of the pineal gland through melatonin secretion on the physiological and morphological parameters of pancreatic islets, we studied the plasma biochemistry and morphological and morphometric characteristics of the endocrine pancreas of male Wistar rats. The animals were distributed into five groups of ten rats each: NC - normal control group; NS -- sham-operated group; Px (25) -- pinealectomised group, studied 15--25 days after surgery; Px (70) -- pinealectomised group, studied 60-70 days after surgery; ALX - alloxan monohydrate-treated group. Data are analyzed statistically by ANOVA and by the Kruskal-Wallis test. Although there was no significant difference in plasma glucose or insulin levels between the Px (25), Px (70) and NC groups, Px (25) animals showed a tendency to increased glucose and reduced insulin levels. The ALX group showed a clear elevation of plasma glucose and a reduction of plasma insulin compared to the other groups. Morphometric analysis showed a larger pancreatic islet area and a lower pancreatic islet density in the pancreas of Px (70) animals and an increase in degenerative pathological processes in the pancreatic islets of the Px (25) and ALX groups. The present results suggest that melatonin, in addition to acting on tissue sensitivity to insulin (as reported in other studies), affects the secretory action of beta cells, as demonstrated by the morphological and morphometric changes observed in pinealectomised animals.
PMID: 11514903 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11452647&dopt=AbstractArkh Patol 2001 May-Jun;63(3):18-21
[Effect of pineal peptides on neuroendocrine system after pinealectomy]
[Article in Russian]
Khavinson VKh, Kvetnoi IM, Popuchiev VV, Iuzhakov VV, Kotlova LN.
St. Petersburg Institute of Bioregulation and Gerontology, 119110, St. Petersburg.
Removal of the pineal gland leads to structural and functional rearrangement of gastric endocrine cells and thyroid C-cells in albino rats, as was shown by immunohistological methods and morphometry. Injection of pineal peptides epithalone and epithalamine eliminated these changes. Biological activity of epithalone is believed to be higher than that of epithalamine.
PMID: 11452647 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11339510&dopt=AbstractJ Pineal Res 2001 May;30(4):213-9
Increased pineal Fdopa uptake is related to severity of Parkinson's disease--a PET study.
Ghaemi M, Rudolf J, Hilker R, Herholz K, Heiss WD.
Klinik fur Neurologie der Universitat zu Koln, Germany.
We investigated regional L-3,4-dihydroxy-6-[18F]fluoro-phenyl-alanine (Fdopa) uptake within the pineal gland using co-registration of Fdopa PET and MRI images. Data from 12 early Parkinson's disease (PD) and 9 advanced PD patients were compared with those from 13 age-matched healthy controls. We found a significant increase of Fdopa influx constants (Ki) and relative Fdopa tracer activity in the pineal gland of PD patients. Additionally, significant correlations were found between Ki and the Hoehn and Yahr (H&Y) scores, and between the relative Fdopa activity and the parameters disease duration, H&Y disease score and Unified Parkinson's Disease Rating Scale (UPDRS). Our studies in patients with PD indicate a participation of extrastriatal dopaminergic structures within the scope of pathophysiological processes in PD. The result may be explained as a compensatory upregulation of monoaminergic transmitter systems outside the basal ganglia. Increased Fdopa uptake in the pineal gland may reflect pineal dysfunction in PD patients.
PMID: 11339510 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11404042&dopt=AbstractExp Gerontol 2001 Jul;36(7):935-45
Experimental research on ageing in Russia.
Anisimov VN.
Gerontological Society of the Russian Academy of Sciences, Laboratory of Carcinogenesis and Ageing, N.N. Petrov Research Institute of Oncology, Pesochny-2, St. Petersburg 189646, Russia. aging@mail.ru
An analysis of the current situation in Russian biogerontology is presented in this paper. There are several active groups in Russia pursuing research in biogerontology capable of producing results publishable in international journals of high repute. The main directions of research on the biology of ageing in this country are prevention of premature ageing, the role of free radicals and of the endocrine system (in particular, the pineal gland) in the mechanisms of ageing, carcinogenesis and ageing and population genetics of ageing. Several groups are conducting fruitful research on the theoretical aspects of the biology of ageing. Only a few teams are focusing on molecular biology and the genetics of ageing. In the past few years, many more researchers in fields highly relevant to gerontology have been attracted by issues in gerontological research. In Russia, the most basic problem facing researchers in biogerontology and other relevant areas is an almost complete absence of support from the State and other decision makers.
PMID: 11404042 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11396829&dopt=AbstractActa Biol Hung 2001;52(1):1-7
A reproductive phase-dependent effect of dietary L-tryptophan on pineal gland and gonad of a nocturnal bird, Indian spotted owlet Athene brama.
Guchhait P, Haldar C.
Department of Zoology, Banaras Hindu University, Varanasi, India.
Unlike other temperate owls, Indian spotted owlet Athene brama possesses a well-developed pineal gland that secrets moderate amount of hydroxy- (serotonin) and methoxy- (melatonin) indoles in circulation. However, in this study, we have reported the response of this endocrine gland to exogenous L-Tryptophan (precursor of the above indoles), and also its effect on gonads of this nocturnal bird. During breeding phase or pineal inactive phase (March), oral treatment of L-Trp (0.5 mg/100 g Bwt/day) significantly increased the pineal gland wt and plasma melatonin (MEL) level, while decreased the gonadal wt and plasma sex steroids levels (estradiol and progesterone in female and testosterone in male). Interestingly, during reproductively quiescent phase or pineal active phase (August), similar amount of L-Trp significantly decreased the plasma MEL level, while increased the above sex steroid levels in plasma. Finally, the results show a clear reproductive phase-dependent inverse effect of L-Trp on pineal gland and gonads for both sexes of the spotted owlets, and suggest that the therapeutic use of this amino acid would be a great advantage for controlling the reproduction of these economically important birds.
PMID: 11396829 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11377981&dopt=AbstractJ Steroid Biochem Mol Biol 2001 May;77(2-3):151-8
The neuroprotective and antiapoptotic effects of melatonin in cerebellar neurons involve glucocorticoid receptor and p130 signal pathways.
Persengiev SP.
Department of Molecular and Cellular Physiology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA. stephen.persengiev@umassmed.edu
Melatonin is an endocrine factor known to affect a number of physiological functions. The present studies have demonstrated an additional activity for pineal melatonin, specifically associated with the survival and differentiation of neuroblasts. Based on experimental data several conclusions might be drawn.
First, melatonin negatively regulates the expression of glucocorticoid receptor (GR) in cerebellar granule neurons.
Second, downregulation of GR is associated with a marked decrease in programmed cell death of the granule neurons.
Third, melatonin upregulates the expression of p130, which is an essential factor for the initiation and maintenance of neuronal development and differentiation.
Thus, melatonin function in postmitotic neurons involves several regulatory pathways with partially overlapping roles. The biological implications are discussed in light of these results.
PMID: 11377981 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11339514&dopt=AbstractJ Pineal Res 2001 May;30(4):243-7
Gene expression of the key enzymes of melatonin synthesis in extrapineal tissues of the rat.
Stefulj J, Hortner M, Ghosh M, Schauenstein K, Rinner I, Wolfler A, Semmler J, Liebmann PM.
Department of Pathophysiology, University of Graz, Austria.
Besides the pineal gland, melatonin is reported to be produced in a number of extrapineal sites, where it could act as an intracellular mediator or paracrine signal in addition to its endocrine effects. In view of the suggested immunoregulatory role of melatonin, we compared lymphoid organs and several other tissues of the rat for their potential to synthesize melatonin. Using the reverse transcription-polymerase chain reaction (RT-PCR) method, we determined the tissue-specific expression of mRNAs encoding two key enzymes of the melatonin biosynthesis: serotonin-N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT). The minimal number of PCR cycles required to obtain a positive signal served as a measure for the abundance of a given mRNA. NAT and HIOMT mRNAs were detected in all tested tissues at high numbers of PCR cycles (40 and 45, respectively). At 35 cycles, only gut, testis, spinal cord, raphe nuclei, stomach fundus and striatum yielded positive signals for both enzymes. In conclusion, the presence of NAT and HIOMT mRNAs in a wide range of tissues corroborates and extends the notion of extrapineal melatonin synthesis. Comparatively low levels of the HIOMT messages in lymphoid organs, however, indicate a limited significance of melatonin synthesis within the immune system.
PMID: 11339514 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11279665&dopt=AbstractMicrosc Res Tech 2001 Apr 1;53(1):2-11
Sensory and endocrine characteristics of the avian pineal organ.
Department of Anatomy (Division II), School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan. sato-t@tsurumi-u.ac.jp
The avian pineal organ represents a transitional type between a photosensory organ of lower vertebrates and the endocrine gland of mammals and shows remarkable changes in its innervation and structure during ontogeny. In the avian pineal organ the progressive reduction of the pinealofugal component and the spectacular increase in pinealopetal sympathetic innervation occur in parallel. In domestic fowl the number of intrapineal AChE-positive (afferent) neurons decreases rapidly during ontogenetic development, whereas the sympathetic innervation becomes more prominent. Furthermore, the end vesicle of the pineal organ is an anatomical entity fully separated from the brain in the adult domestic fowl, as observed in some mammalian pineals. The avian pineal organ contains several types of photoreceptors with different photopigments and the synthesis of melatonin, the pineal hormone, is controlled by light. Immunoreactivity for photopigments is reduced during the posthatching development of chicken, whereas neuron-specific enolase (NSE)-immunoreactive pinealocytes increase remarkably in number in the end-vesicle of the domestic fowl with age, followed by a gradual expansion toward the proximal portion. NSE is the most acidic isoenzyme of the glycolytic enzyme enolase and is useful as a cytoplasmic marker of neurons and neuroendocrine tissue. The above-mentioned findings reflect the sequence of changes leading from pineal sense organs to pineal gland. The demonstration of melatonin receptors in a variety of avian peripheral tissues suggest a possible direct action of melatonin on the physiological functions of different organ systems in response to internal and external stimuli. Copyright 2001 Wiley-Liss, Inc.
Publication Types:
- Review
- Review, Tutorial
PMID: 11279665 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11169912&dopt=AbstractAnat Rec 2001 Feb 1;262(2):176-85
Ultrastructural and morphometric study of the Sertoli cell of the viscacha (Lagostomus maximus maximus) during the annual reproductive cycle.
Munoz EM, Fogal T, Dominguez S, Scardapane L, Piezzi RS.
Catedra de Histologia y Embriologia, Universidad Nacional de San Luis, San Luis, Argentina.
Changes in the morphology of viscacha Sertoli cells were studied during the annual reproductive cycle. Sertoli cells exhibited marked nuclear and cytoplasmic changes. Seasonal variation in nuclear size and shape, chromatin texture, and nucleolus characteristics was observed. The seasonal patterns of the volume densities of the endoplasmic reticulum (ER), mitochondria, Golgi complex, dense bodies and lipid inclusions were distinct. Morphometric analysis revealed that the Golgi complex is the organelle most sensitive to seasonal change. It declined drastically in the regressed testes and its recovery was slow. The ER and mitochondria exhibited seasonal variations in their pattern and content, that was minimal during winter. In contrast, an accumulation of lipid and dense bodies, such as primary and secondary lysosomes, accompanied the spermatogenic arrest. The volume densities of both organelles were maximum during the restoration of spermatogenesis. The length and organization of the inter-Sertoli junctions also changed with the reproductive cycle. The Sertoli cell number per tubular cross section decreased significantly during the testicular regression, coincident with the presence of Sertoli cells with marked signs of involution. The degree of regression and recovery exhibited by the viscacha Sertoli cells was closely related to that shown by the associated germ cells. Therefore, seasonal endocrine fluctuations and local factors could be involved in the regulation of the morphological and functional characteristics of the viscacha Sertoli cells. These hormonal fluctuations are synchronized by the photoperiod through the pineal gland and its hormone, melatonin. Copyright 2001 Wiley-Liss, Inc.
PMID: 11169912 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11767288&dopt=AbstractJ Neurooncol 2001 Sep;54(3):211-7
Epidemiology of germ cell tumors in Asia of pineal region tumor.
Nomura K.
Neurosurgical Division, National Cancer Center Hospital, Tokyo, Japan. knomura@ncc.go.jp
A higher incidence of pineal region tumors in Asian countries compared to Western countries has been reported. In the Brain Tumor Registry of Japan (BTRJ), there were 38,273 primary brain tumors except those of unknown histology (1123 cases) registered in the period between 1984 and 1993, in which 807 pineal region tumors with 104 unknown histology were registered in BTRJ. Of these pineal region tumors, germ cell tumors had the highest frequency, 70.3%, followed by pineal parenchymal tumors, 12.0%; pineocytoma in 7.8% and pineoblastoma in 4.2%. Limited to germ cell tumors, germinoma was 68.0%, then teratoma including malignant teratoma, had the second high frequency, 14.7% in pineal region. While data reported by Allaire et al. and Edwards et al. revealed that the incidence of germinoma was 88.6%, 52.4% of germ cell tumors in pineal region in France and in USA, respectively. Although number of cases is very small, it is suggested that the percentage of germinoma in germ cell tumors in the pineal region might be almost the same in Western countries as in Asian countries, and the occurrence of germ cell tumors in the pineal region was much higher than those in Asia. Age and gender distribution of pineal region tumors indicated that germ cell tumors and pineocytoma showed a high incidence in males and in children. Most of malignant pineal region tumors other than germinomas showed poor prognosis, but recent progress in surgical techniques and effective chemotherapy will improve the prognosis.
PMID: 11767288 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11550795&dopt=AbstractProg Nucleic Acid Res Mol Biol 2001;69:205-47
The ROR nuclear orphan receptor subfamily: critical regulators of multiple biological processes.
Jetten AM, Kurebayashi S, Ueda E.
Cell Biology Section, Division of Intramural Research, National Institute of Environmental Health Sciences, National Institute of Health, Research Triangle Park, North Carolina 27709, USA. jetten@niehs.nih.gov
The nuclear receptor superfamily, a group of structurally related, ligand-dependent transcription factors, includes a large number of orphan receptors for which no ligand has yet been identified. These proteins function as key regulators of many physiological processes that occur during embryonic development and in the adult. The retinoid-related orphan receptors (RORs) alpha, beta, and gamma comprise one nuclear orphan receptor gene subfamily. RORs exhibit a modular structure that is characteristic for nuclear receptors; the DNA-binding domain is highly conserved and the ligand-binding domain is moderately conserved among RORs. By a combination of alternative promoter usage and exon splicing, each ROR gene generates several isoforms that differ only in their amino terminus. RORs bind as monomers to specific ROR response elements (ROREs) consisting of the consensus core motif AGGTCA preceded by a 5-bp A/T-rich sequence. RORE-dependent transcriptional activation by RORs is cell type-specific and mediated through interactions with nuclear cofactors. RORs have been shown to interact with certain corepressors as well as coactivators, suggesting that RORs are not constitutively active but that their activity is under some regulatory control. RORs likely can assume at least two different conformations: a repressive state, which allows interaction with corepressor complexes, and an active state, which promotes binding of coactivator complexes. Whether the transition between these two states is regulated by ligand binding and/or by phosphorylation remains to be determined. Ca2+/calmodulin-dependent kinase IV (CaMKIV) can dramatically enhance ROR-mediated transcriptional activation. This stimulation involves CaMKIV-mediated phosphorylation not of RORs, but likely of specific nuclear cofactors that interact with RORs. RORalpha is widely expressed. In the cerebellum, its expression is limited to the Purkinje cells. RORalpha-/- mice and the natural RORalpha-deficient staggerer mice exhibit severe cerebellar ataxia due to a defect in Purkinje cell development. In addition, these mice have thin long bones, suggesting a role for RORalpha in bone metabolism, and develop severe atherosclerosis when placed on a high-fat diet. Expression of RORbeta is very restricted. RORbeta is highly expressed in different parts of the neurophotoendocrine system, the pineal gland, the retina, and suprachiasmatic nuclei, suggesting a role in the control of circadian rhythm. This is supported by observations showing alterations in circadian behavior in RORbeta-/- mice. RORgamma, which is most highly expressed in the thymus, plays an important role in thymopoiesis. Thymocytes from RORgamma-/- mice undergo accelerated apoptosis. The induction of apoptosis is, at least in part, due to a down-regulation of the expression of the antiapoptotic gene Bcl-XL. In addition to the thynic phenotype, RORgamma-/- mice lack lymph nodes, indicating that RORgamma is essential for lymph node organogenesis. Overexpression of RORgamma has been shown to inhibit T cell receptor-mediated apoptosis in T cell hybridomas and to repress the induction of Fas-ligand and interleukin 2. These studies demonstrate that RORs play critical roles in the regulation of a variety of physiological processes. Further characterization of the mechanisms of action of RORs will not only lead to the identification of ROR target genes and provide additional insight into their normal physiological functions, but will also determine their roles in disease.
Publication Types:
- Review
- Review, Academic
PMID: 11550795 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11337619&dopt=AbstractSpine 2001 May 1;26(9):1014-21
Correlation between the age of pinealectomy and the development of scoliosis in chickens.
Inoh H, Kawakami N, Matsuyama Y, Aoki T, Kanemura T, Natsume N, Iwata H.
Department of Orthopaedic Surgery, Nagoya Daiichi Red Cross Hospital, Nagoya, Japan. inoh@rb3.so-net.ne
STUDY DESIGN: Pinealectomy induces experimental scoliosis in chickens. This study analyzed the correlation between the age at which pinealectomy was performed and the development of scoliosis in chickens.OBJECTIVE: To investigate the differences in the rate or magnitude of scoliosis and the type of curvature in chickens pinealectomized at different times after hatching.
SUMMARY OF BACKGROUND DATA: Scoliosis develops in almost all chickens pinealectomized within 3 days after hatching, but there are no data on whether the condition will develop in chickens pinealectomized earlier or later after hatching.
METHODS: In this study, 106 female white leghorn chickens were divided into six groups: four pinealectomy groups (pinealectomy was performed 2, 4, 11, or 18 days after hatching in Groups P-2, P-4, P-11, and P-18, respectively), a control group (Group C), and a sham operation group (Group S). Ventrodorsal radiographs of the spine were taken at 4-week intervals until the age of 12 weeks. At 12 weeks, a 1-mL sample of blood was taken from the heart at the middle of the dark cycle, and the serum melatonin concentration was measured by radioimmunoassay.
RESULTS: At the age of 12 weeks, scoliosis was present in 63.6% of the chickens in Group P-2, 72.7% in Group P-4, 81% in Group P-11, and 70% in Group P-18, and the Cobb angles in the scoliotic chickens averaged 32.6, 29.8, 23.8, and 22.3 degrees in the respective groups. There were no significant differences in the rate or magnitude of scoliosis and the type of curvature among the pinealectomy groups at the age of 12 weeks. At the age of 12 weeks, the serum melatonin levels at the middle of the dark cycle in the pinealectomized chickens were significantly lower than those of chickens in Groups C and S. However, there were no differences in the serum melatonin levels between scoliotic and nonscoliotic pinealectomized chickens.
CONCLUSIONS: Findings from this study show that scoliosis develops in 60% to 80% of chickens pinealectomized within 18 days after hatching, and that scoliotic development is not influenced by the age at which pinealectomy is performed. However, this study suggests that melatonin plays a complicated role in spinal development, inasmuch as the serum melatonin levels after pinealectomy approximated zero. Yet scoliosis did not develop in all pinealectomized chickens.
PMID: 11337619 [PubMed - indexed for MEDLINE]
http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11335879&dopt=AbstractNeuroendocrinol Lett 2001;22(1):45-7
Anti-angiogenic activity of melatonin in advanced cancer patients.
Lissoni P, Rovelli F, Malugani F, Bucovec R, Conti A, Maestroni GJ.
Division of Radiation Oncology, San Gerardo Hospital, 20052 Monza, Milan, Italy.
OBJECTIVES: The anticancer activity of the indole melatonin has been explained to be due to its immunomodulatory, anti-prolferative and anti-oxidant effects, whereas at present no data are available about its possible influence on the angiogenesis, which has been shown to be one of the main biological mechanisms responsible for tumor dissemination. Vascular endothelial growth factor (VEGF) is the most active angiogenic factor, and the evidence of abnormally high blood levels or VEGF has been proven to be associated with poor prognosis in cancer patients. To investigate the influence of melatonin on angiogenesis, in this preliminary study we have evaluated the effects of melatonin therapy on VEGF blood levels in advanced cancer patients.MATERIAL & METHODS: The study included 20 metastatic patients, who progressed on previous conventional antitumor therapies and for whom no other effective treatment was available. Melatonin was given orally at 20 mg/day in the evening for at least 2 months. Serum levels of VEGF were measured by an enzyme immunoassay on venous blood samples collected at 15-day intervals.
RESULTS: The clinical response consisted of minor response (MR) in 2, stable disease (SD) in 6 and progressive disease (PD) in the remaining 12 patients. VEGF mean levels decreased on therapy, without, however, statistical differences with respect to the pre-treatment values. In contrast, by evaluating changes in VEGF levels in relation to the clinical response, non-progressing patients (MR + SD) showed a significant decline in VEGF mean concentrations, whereas no effect was achieved in progressing patients.
CONCLUSIONS: This study, by showing that melatonin-induced control or the neoplastic growth is associated with a decline in VEGF secretion, would suggest that the pineal hormone may control tumor growth at least in part by acting as a natural anti-angiogenic molecule, with a following opposition or angiogenesis-dependent cancer proliferation.
Publication Types:
- Clinical Trial
PMID: 11335879 [PubMed - indexed for MEDLINE]