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BMC Endocrine Disorders Oct 2023The pineal lesion affecting melatonin is a rare cause of central precocious puberty by decreasing the inhibition of hypothalamic-pituitary-gonadal axis. Germ cell tumor... (Review)
Review
BACKGROUND
The pineal lesion affecting melatonin is a rare cause of central precocious puberty by decreasing the inhibition of hypothalamic-pituitary-gonadal axis. Germ cell tumor secreting human chorionic gonadotropin is a rare cause of peripheral puberty.
CASE PRESENTATION
A 5.8-year-old male presented facial hair and phallic growth, deepened voice, and accelerated growth velocity for 6 months. The elevated human chorionic gonadotropin level with undetectable gonadotropin levels indicated peripheral precocious puberty. Brain imaging revealed a pineal mass and further pathology indicated the diagnosis of teratoma. During chemoradiotherapy with operation, the elevated human chorionic gonadotropin level reduced to normal range, while the levels of gonadotropins and testosterone increased. Subsequently, progressing precocious puberty was arrested with gonadotrophin-releasing hormone analog therapy. Previous cases of transition from peripheral precocious puberty to central precocious puberty were reviewed. The transitions were caused by the suddenly reduced feedback inhibition of sex steroid hormones on gonadotropin releasing hormone and gonadotropins.
CONCLUSIONS
For patients with human chorionic gonadotropin-secreting tumors, gonadotropin levels increase prior to sex steroid decrease, seems a sign of melatonin-related central PP related to melatonin.
Topics: Child, Preschool; Humans; Male; Chorionic Gonadotropin; Gonadal Steroid Hormones; Gonadotropin-Releasing Hormone; Melatonin; Neoplasms, Germ Cell and Embryonal; Puberty, Precocious
PubMed: 37884982
DOI: 10.1186/s12902-023-01494-0 -
International Journal of Molecular... Oct 2023Melatonin (-acetyl-5-methoxytryptamine, MEL), its kynurenic (-acetyl--formyl-5-methoxykynurenine, AFMK) and indolic derivatives (6-hydroxymelatonin, 6(OH)MEL and...
Melatonin (-acetyl-5-methoxytryptamine, MEL), its kynurenic (-acetyl--formyl-5-methoxykynurenine, AFMK) and indolic derivatives (6-hydroxymelatonin, 6(OH)MEL and 5-methoxytryptamine, 5-MT) are endogenously produced in human epidermis. Melatonin, produced by the pineal gland, brain and peripheral organs, displays a diversity of physiological functions including anti-inflammatory, immunomodulatory, and anti-tumor capacities. Herein, we assessed their regulatory effect on melanogenesis using amelanotic (A375, Sk-Mel-28) and highly pigmented (MNT-1, melanotic) human melanoma cell lines. We discovered that subjected compounds decrease the downstream pathway of melanin synthesis by causing a significant drop of cyclic adenosine monophosphate (cAMP) level, the microphthalmia-associated transcription factor (MITF) and resultant collapse of tyrosinase (TYR) activity, and melanin content comparatively to -phenylthiourea (PTU, a positive control). We observed a reduction in pigment in melanosomes visualized by the transmission electron microscopy. Finally, we assessed the role of G-protein-coupled seven-transmembrane-domain receptors. Obtained results revealed that nonselective MT1 and MT2 receptor antagonist (luzindole) or selective MT2 receptor antagonist (4-P-PDOT) did not affect dysregulation of the melanin pathway indicating a receptor-independent mechanism. Our findings, together with the current state of the art, provide a convenient experimental model to study the complex relationship between metabolites of melatonin and the control of pigmentation serving as a future and rationale strategy for targeted therapies of melanoma-affected patients.
Topics: Humans; Melatonin; Melanins; 5-Methoxytryptamine; Receptor, Melatonin, MT2; Melanoma; Monophenol Monooxygenase
PubMed: 37834395
DOI: 10.3390/ijms241914947 -
European Journal of Epidemiology Oct 2023Light-at-night triggers the decline of pineal gland melatonin biosynthesis and secretion and is an IARC-classified probable breast-cancer risk factor. We applied a...
Light-at-night triggers the decline of pineal gland melatonin biosynthesis and secretion and is an IARC-classified probable breast-cancer risk factor. We applied a large-scale molecular epidemiology approach to shed light on the putative role of melatonin in breast cancer. We investigated associations between breast-cancer risk and polymorphisms at genes of melatonin biosynthesis/signaling using a study population of 44,405 women from the Breast Cancer Association Consortium (22,992 cases, 21,413 population-based controls). Genotype data of 97 candidate single nucleotide polymorphisms (SNPs) at 18 defined gene regions were investigated for breast-cancer risk effects. We calculated adjusted odds ratios (ORs) and 95% confidence intervals (CI) by logistic regression for the main-effect analysis as well as stratified analyses by estrogen- and progesterone-receptor (ER, PR) status. SNP-SNP interactions were analyzed via a two-step procedure based on logic regression. The Bayesian false-discovery probability (BFDP) was used for all analyses to account for multiple testing. Noteworthy associations (BFDP < 0.8) included 10 linked SNPs in tryptophan hydroxylase 2 (TPH2) (e.g. rs1386492: OR = 1.07, 95% CI 1.02-1.12), and a SNP in the mitogen-activated protein kinase 8 (MAPK8) (rs10857561: OR = 1.11, 95% CI 1.04-1.18). The SNP-SNP interaction analysis revealed noteworthy interaction terms with TPH2- and MAPK-related SNPs (e.g. rs1386483 ∧ rs1473473 ∧ rs3729931: OR = 1.20, 95% CI 1.09-1.32). In line with the light-at-night hypothesis that links shift work with elevated breast-cancer risks our results point to SNPs in TPH2 and MAPK-genes that may impact the intricate network of circadian regulation.
Topics: Humans; Female; Breast Neoplasms; Melatonin; Bayes Theorem; Polymorphism, Single Nucleotide; Logistic Models; Case-Control Studies; Genetic Predisposition to Disease
PubMed: 37789226
DOI: 10.1007/s10654-023-01048-7 -
Acta Neuropathologica Dec 2023
Genetical and epigenetical profiling identifies two subgroups of pineal parenchymal tumors of intermediate differentiation (PPTID) with distinct molecular, histological and clinical characteristics.
Topics: Humans; Pinealoma; Pineal Gland; Brain Neoplasms
PubMed: 37776353
DOI: 10.1007/s00401-023-02638-1 -
Pharmaceuticals (Basel, Switzerland) Sep 2023Melatonin is a hormone secreted mainly by the pineal gland and acts through the Mel1A and Mel1B receptors. Among other actions, melatonin significantly increases...
Melatonin is a hormone secreted mainly by the pineal gland and acts through the Mel1A and Mel1B receptors. Among other actions, melatonin significantly increases osteogenesis during bone regeneration. Human adipose-derived mesenchymal stem cells (ADSCs) are also known to have the potential to differentiate into osteoblast-like cells; however, inefficient culturing due to the loss of properties over time or low cell survival rates on scaffolds is a limitation. Improving the process of ADSC expansion in vitro is crucial for its further successful use in bone regeneration. This study aimed to assess the effect of melatonin on ADSC characteristics, including osteogenicity. We assessed ADSC viability at different melatonin concentrations as well as the effect on its receptor inhibitors (luzindole or 4-P-PDOT). Moreover, we analyzed the ADSC phenotype, apoptosis, cell cycle, and expression of and receptors, and its potential for osteogenic differentiation. We found that ADSCs treated with melatonin at a concentration of 100 µM had a higher viability compared to those treated at higher melatonin concentrations. Melatonin did not change the phenotype of ADSCs or induce apoptosis and it promoted the activity of some osteogenesis-related genes. We concluded that melatonin is safe, non-toxic to normal ADSCs in vitro, and can be used in regenerative medicine at low doses (100 μM) to improve cell viability without negatively affecting the osteogenic potential of these cells.
PubMed: 37765045
DOI: 10.3390/ph16091236 -
Journal of Personalized Medicine Aug 2023Melatonin (MLT), a pineal gland hormone, not only regulates circadian and seasonal rhythms, but also plays an important role in many aspects of human physiology and...
Melatonin (MLT), a pineal gland hormone, not only regulates circadian and seasonal rhythms, but also plays an important role in many aspects of human physiology and pathophysiology. MLT is of great interest as a natural substance with anti-cancer activities. The aim of this study was to assess the cytotoxicity and apoptosis of MLT, used alone or in combination with one of the most active anti-cancer drugs, doxorubicin (DOX), and a well-known anti-inflammatory drug, dexamethasone (DEX), on a diffuse large B-cell lymphoma (DLBCL)-derived cell line. The cytotoxicity and cell cycle distribution were measured using propidium iodide staining, while apoptosis was assessed using the annexin-V binding method. Additionally, to elucidate the mechanisms of action, caspase-3, -8, and -9 and a decline in the mitochondrial potential were determined using flow cytometry. MLT inhibited cell viability as well as induced apoptosis and cell cycle arrest at the G0/G1 phase. The pro-apoptotic effect was exerted through both the mitochondrial and caspase-dependent pathways. Furthermore, we observed increased cytotoxic and pro-apoptotic activity as well as the modulation of the cell cycle after the combination of MLT with DOX, DEX, or a combination of DOX + DEX, compared with both drugs or MLT used alone. Our findings confirm that MLT is a promising in vitro anti-tumour agent that requires further evaluation when used with other drugs active against DLBCL.
PubMed: 37763082
DOI: 10.3390/jpm13091314 -
International Journal of Surgery... Dec 2023The pineal region tumors are challenging for neurosurgeons and can lead to secondary hydrocephalus. The introduction of the exoscope has provided clinical interventions...
BACKGROUND
The pineal region tumors are challenging for neurosurgeons and can lead to secondary hydrocephalus. The introduction of the exoscope has provided clinical interventions with high image quality and an ergonomic system for pineal region tumor operations. In this study, the authors describe the exoscopic approach used to facilitate the surgical resection of pineal region tumors and relieve hydrocephalus.
MATERIALS AND METHODS
In this retrospective cohort study, we consecutively reviewed the clinical and radiological data of 25 patients with pineal region lesions who underwent three-dimensional exoscopic tumor resection at a single center.
RESULTS
The patient cohort consisted of 16 males and 9 females, with an average age of 34.6 years (range, 6-62 years; 8 cases aged ≤18). Pathological examination confirmed eight pineal gland tumors, four gliomas, nine germ cell neoplasms, two ependymomas, and two metastatic tumors. Preoperative hydrocephalus was present in 23 patients. Prior to tumor resection, external ventricular drainage (EVD) with Ommaya reservoir implantation was performed in 17 patients. Two patients received preoperative endoscopic third ventriculostomy (ETV), and five patients received a ventriculoperitoneal (VP) shunt, including one who received both procedures. Gross total resection was achieved in 19 patients (76%) in the 'head-up' park bench position using the exoscope. Eight patients (31.6%) with third ventricle invasion received subtotal resection, mainly in glioma cases, which was higher than those without invasion (0%), but not statistically significant ( P =0.278, Fisher's exact test). No new neurological dysfunction was observed after surgery. Two patients (8%) developed intracranial and pulmonary infections, and two patients (8%) suffered from pneumothorax. Hydrocephalus was significantly relieved in all patients postoperatively, and four patients with relapse hydrocephalus were cured during the long-term follow-up. Postoperative adjuvant management was recommended for indicated patients, and a mean follow-up of 24.8±14.3 months showed a satisfied outcome.
CONCLUSIONS
The exoscope is a useful tool for pineal region tumor resection and hydrocephalus relief, particularly with posterior third ventricle invasion, as total resection could be achieved without obvious complication. The special superiority of the exoscope for the indicated pineal region tumors should be highlighted.
Topics: Male; Female; Humans; Adult; Pinealoma; Retrospective Studies; Treatment Outcome; Neoplasm Recurrence, Local; Pineal Gland; Glioma; Ventriculostomy; Third Ventricle; Hydrocephalus; Brain Neoplasms
PubMed: 37755386
DOI: 10.1097/JS9.0000000000000707 -
Journal of the Neurological Sciences Oct 2023The present study aimed to determine prevalence of non-hydrocephalic pineal cysts of different size and morphology in healthy individuals. In a cohort of healthy...
The present study aimed to determine prevalence of non-hydrocephalic pineal cysts of different size and morphology in healthy individuals. In a cohort of healthy individuals who as part of research volunteered to undergo magnetic resonance imaging (MRI) of the brain, we performed a systematic search for occurrence of pineal cysts of different sizes, morphology and evidence of crowding of the pineal recess. Degree of crowding in the pineal recess was estimated by the imaging biomarkers anterior-posterior diameter and cyst-tectum-splenium (CTS) ratio at midsagittal MRI. The study included a cohort of 994 healthy individuals, aged 47.0 ± 21.1 years in whom a pineal cyst was demonstrated in 337/994 (37.5%) individuals. A small cyst within a mainly solid gland was observed in 252/994 (25.4%) subjects and a mainly cystic gland in121/994 (12.2%). The pineal cysts were more frequent in women than men, and were associated with age, though not with reduced prevalence in aged individuals, as previously reported. Cysts with maximum anterior-posterior diameter ≥ 10 mm were seen in 51/994 (5.1%) individuals, and with CTS ratio ≥ 0.9 in 16/994 (1.6%) individuals. The occurrence of pineal cysts is frequent and is seen more frequently in women. It usually presents as a small cyst in a predominantly solid gland; however, pineal cysts causing crowding of the pineal recess with a CTS ratio ≥ 0.9 was seen in merely 1.6% of participants.
PubMed: 37741123
DOI: 10.1016/j.jns.2023.120801 -
BMC Genomics Sep 2023The mitochondria are central in the cellular response to changing environmental conditions resulting from disease states, environmental exposures or normal physiological...
The mitochondria are central in the cellular response to changing environmental conditions resulting from disease states, environmental exposures or normal physiological processes. Although the influences of environmental stressors upon the nuclear epigenome are well characterized, the existence and role of the mitochondrial epigenome remains contentious. Here, by quantifying the mitochondrial epigenomic response of pineal gland cells to circadian stress, we confirm the presence of extensive cytosine methylation within the mitochondrial genome. Furthermore, we identify distinct epigenetically plastic regions (mtDMRs) which vary in cytosinic methylation, primarily in a non CpG context, in response to stress and in a sex-specific manner. Motifs enriched in mtDMRs contain recognition sites for nuclear-derived DNA-binding factors (ATF4, HNF4A) important in the cellular metabolic stress response, which we found to be conserved across diverse vertebrate taxa. Together, these findings suggest a new layer of mito-nuclear interaction in which the nuclear metabolic stress response could alter mitochondrial transcriptional dynamics through the binding of nuclear-derived transcription factors in a methylation-dependent context.
Topics: Female; Male; Animals; Vertebrates; Mitochondria; Epigenome; Epigenomics; Genome, Mitochondrial; Mitomycin
PubMed: 37736707
DOI: 10.1186/s12864-023-09668-9 -
Nature Sep 2023The neurocranium is an integral part of the vertebrate head, itself a major evolutionary innovation. However, its early history remains poorly understood, with great...
The neurocranium is an integral part of the vertebrate head, itself a major evolutionary innovation. However, its early history remains poorly understood, with great dissimilarity in form between the two living vertebrate groups: gnathostomes (jawed vertebrates) and cyclostomes (hagfishes and lampreys). The 100 Myr gap separating the Cambrian appearance of vertebrates from the earliest three-dimensionally preserved vertebrate neurocrania further obscures the origins of modern states. Here we use computed tomography to describe the cranial anatomy of an Ordovician stem-group gnathostome: Eriptychius americanus from the Harding Sandstone of Colorado, USA. A fossilized head of Eriptychius preserves a symmetrical set of cartilages that we interpret as the preorbital neurocranium, enclosing the fronts of laterally placed orbits, terminally located mouth, olfactory bulbs and pineal organ. This suggests that, in the earliest gnathostomes, the neurocranium filled out the space between the dermal skeleton and brain, like in galeaspids, osteostracans and placoderms and unlike in cyclostomes. However, these cartilages are not fused into a single neurocranial unit, suggesting that this is a derived gnathostome trait. Eriptychius fills a major temporal and phylogenetic gap in our understanding of the evolution of the gnathostome head, revealing a neurocranium with an anatomy unlike that of any previously described vertebrate.
Topics: Animals; Fossils; Hagfishes; Imaging, Three-Dimensional; Lampreys; Mouth; Olfactory Bulb; Phylogeny; Pineal Gland; Skull; Tomography Scanners, X-Ray Computed; Vertebrates; Colorado; Cartilage
PubMed: 37730987
DOI: 10.1038/s41586-023-06538-y