Endocrine - Pineal Development
|Embryology - 16 Jan 2018 Expand to Translate|
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- 1 Introduction
- 2 Some Recent Findings
- 3 Development Overview
- 4 Melatonin
- 5 Innervation
- 6 Molecular Development
- 7 Abnormalities
- 8 Histology
- 9 Images
- 10 References
- 11 External Links
- 12 Additional Images
- 13 Terms
- 14 Glossary Links
The pineal gland (epiphysis cerebri) has an important role in the sleep/wake daily cycle (circadian), high melatonin plasma levels at nighttime and very low levels at daytime, and reproductive development. The gland is thought to evolutionarily to have been positioned as to be exposed to light, and hence remains a regulator of cyclic rhythms associated with day/night and day length. The pineal hormone (melatonin) has targets both in the nervous system and in many different peripheral tissues.
The embryo and fetus pineal does not produce significant amounts of melatonin, though the maternal pineal gland produces melatonin in the normal circadian fashion and this melatonin can cross both the placenta and blood-brain barrier. In other species, maternal melatonin crosses the placenta into fetal circulation and may provide photoperiodic information during fetal development that influences later postnatal circadian (daily day/night) and seasonal (day length) rhythms. The pineals of non-mammalian vertebrates are photoreceptive, whereas those of mammals do not normally respond to directly light.
Postnatally in humans, the melatonin levels in premature infants is lower and delayed, but not different when calculated from conception date. Other factors such as preeclampsia, growth restriction, and nursery lighting can cause altered rhythm development. The same study has also shown that full-term infants born at home and full-term twins born in the hospital had significantly lower metabolite excretion levels than hospital-born singleton infants at the same ages despite similar body weights.
- part of epithalmus - neurons, glia and pinealocytes
- pinealocytes secrete melatonin - cyclic nature of activity, melatonin lowest during daylight
- inhibit hypothalamic secretion of GnRH until puberty, pineal gland then rapidly regresses.
- other activities - possibly gamete maturation, antioxidant effect, protect neurons?
Lecture - Endocrine Development | Lecture - Head Development | 1937 Human Pineal | Category:Pineal
Note that there are many clinical studies investigating the possible role of melatonin in diverse health areas, from oxygen starvation at birth through to neural effects in old age.
Some Recent Findings
|More recent papers|
This table shows an automated computer PubMed search using the listed sub-heading term.
References listed on the rest of the content page and the associated discussion page (listed under the publication year sub-headings) do include some editorial selection based upon both relevance and availability.
Ágnes Csáki, Viktória Vereczki, Ákos Lukáts, Zsolt Boldogkői, Anna Sebestyén, Zita Puskár, Katalin Köves Ontogenesis of the pinealo-retinal neuronal connection in albino rats. Neurosci. Lett.: 2017; PubMed 29217260
Bianka Bojková, Karol Kajo, Terézia Kisková, Peter Kubatka, Pavol Žúbor, Peter Solár, Martin Péč, Marián Adamkov Metformin and melatonin inhibit DMBA-induced mammary tumorigenesis in rats fed a high-fat diet. Anticancer Drugs: 2017; PubMed 29200002
Dongrui Ji, Su Wang, Mingyue Li, Shicui Zhang, Hongyan Li Involvement of Lypge in the formation of eye and pineal gland in zebrafish. Gene: 2017; PubMed 29196253
Bharati Sinha, Qiaofeng Wu, Wei Li, Yanyang Tu, Ana C Sirianni, Yanchun Chen, Jiying Jiang, Xinmu Zhang, Shuanhu Zhou, Wu Chen, Russel J Reiter, Simon Manning, Nirav J Patel, Ali M Aziz-Sultan, Terri E Inder, Robert M Friedlander, Jianfang Fu, Xin Wang Protection of melatonin in experimental models of newborn hypoxic-ischemic brain injury through MT1 receptor. J. Pineal Res.: 2017; PubMed 28796402
Darío Acuña-Castroviejo, Ibtissem Rahim, Carlos Acuña-Fernández, Marisol Fernández-Ortiz, Jorge Solera-Marín, Ramy K A Sayed, María E Díaz-Casado, Iryna Rusanova, Luis C López, Germaine Escames Melatonin, clock genes and mitochondria in sepsis. Cell. Mol. Life Sci.: 2017; PubMed 28785808
- Neuroectoderm - prosenecephalon then diencephalon
- caudal roof, median diverticulum, epiphysis
- Initially a hollow diverticulum, cell proliferation to solid, pinealocytes (neuroglia), cone-shaped gland innervated by epithalamus
Epithalamus consists of the pineal gland and habenular nuclei
| Fetal Pineal Anatomy
Superior (dorsal) view of the diencephalic-mesencephalic area of a 3.5-month-old human fetus.
The third ventricle (3 ventr) without pial covering is seen to the right in the micrograph.
The small pineal gland is a small protuberance (arrow) and merging via the broad stalk with the habenula (Ha). Sup col.: superior colliculus.
Bar = 2 mm.
- Melatonin is synthesized from the amino acid tryptophan within the pinealocytes.
- Serotonin is first acetylated by aryl alkylamine N-acetyltransferase (AA-NAT), then converted to melatonin by acetyl serotonin methyl transferase (ASMT also known as hydroxyindole O-methyltransferase or HIOMT).
- Melatonin release is stimulated by darkness and inhibited by light and is said to have neurological "chronobiotic" properties for resynchronization of sleep and circadian rhythms disturbances. In the periphery, melatonin is also involved in the regulation of several complex cycles: seasonal reproduction, body weight and energy balance.
- Melatonin levels can be monitored by urinary excretion of the melatonin metabolite 6-sulfatoxymelatonin (aMT.6S).
The hormone melatonin acts through receptors (high affinity G protein-coupled) embedded in the cell membrane. Three different receptor subtypes have been identified in mammals: MT1 (Mel 1a) and MT2 (Mel 1b) and a putative binding site called MT3.
- MT1 - expressed in humans in the pars tuberalis of the pituitary gland and the suprachiasmatic nuclei of the hypothalamus.
- MT2 - expressed in the retina.
- MT3 - expressed in many non-mammalian vertebrates in a range of brain areas.
The gland is connected to the hypothalamus suprachiasmatic nucleus (SCN) central rhythm generator through a multi-synaptic pathway.
Nerve fibers innervating the mammalian pineal gland originate from perikarya located in the sympathetic superior cervical ganglion, the parasympathetic sphenopalatine and otic ganglia, as well as by nerve fibers originating in the central nervous system.
- sympathetic nerves - contain norepinephrine and neuropeptide Y as neurotransmitters
- parasympathetic nerves - contain vasoactive intestinal peptide and peptide histidine isoleucine
- trigeminal ganglion - containing substance P, calcitonin gene-related peptide, and pituitary adenylate cyclase-activating peptide
Mouse pineal gland (E15 to E21)
| The pineal gland develops from neuroepithelial cells that express the transcription factor Pax6 and the intermediate filament vimentin.
Panels display confocal microscopy of immunolabeled sagittal sections of rat pineal gland (PG) from embryonic day (E) 15 to E21.
Pineal organogenesis begins around E15 as an evagination of the neuroepithelium in the dorsal diencephalon that is densely populated by Pax6-expressing cells (green). The developing PG becomes a tubular extension at E16. The orientation of Pax6/VIM+ cells is radial at these stages. At E17 the pineal neuroepithelium begins to fold and fuses at the midline. After fusion of the neuroepithelium, double immunolabeled rosette-like structures are visible in the E18-E21 developing PG. At E21 the PG has developed into a recognizable globular structure. (A1-G1) 20x; scale bar: 75 μm. (A2-G4) 60x; scale bar: 25 μm. PC, posterior commissure. SCO, subcommissural organ. 3v, third ventricle.
- Nodal - zebrafish required for dorsal convergence of pineal precursors.
- Pax6 - rat pineal gland from E16, peak expression around E18.
- Fgf8a - zebrafish epithalamus acts permissively to promote parapineal fate.
- DARPP-32 (Dopamine- and cAMP-regulated phosphoprotein of 32 kDa) is involved in the retinal pathway transmitting photic information that resets the circadian clock.
Links: Molecular Development
- Pineal Hypoplasia associated with retinal disease.
- Pineal Tumours in children are associated with abnormal puberty development.
- Astrocytes - small dark nuclei
- Pinealocytes - most nuclei present, larger lighter and round nuclei surrounded by a broad rim of light cytoplasm
- Endothelial cells - nuclei in association with the vessels and capillaries traversing the tissue.
- Cytoplasmic processes - "stringy" appearance from both pinealocytes and astrocytes
- Links: large histology image
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Cooper, ERA. The Human Pineal Gland and Pineal Cysts (1932)
|Fig. 1. Sagittal midline section through head of 25 mm. embryo. x 8. A, anlage of pineal gland in the form of a backward hollowextension. B, anlage of posterior commissure. C, third ventricle. D, pituitary body.||Fig. 2. Sagittal section through head of 35 mm. embryo, not quite median. x 10. A, anterior anlage of pineal. B, posterior anlage with divertioulum pineale. C, posterior commisaure. D, third ventricle. E, pituitary body.|
- D J Kennaway, F C Goble, G E Stamp Factors influencing the development of melatonin rhythmicity in humans. J. Clin. Endocrinol. Metab.: 1996, 81(4);1525-32 PubMed 8636362
- María P Ibañez Rodriguez, Stephen C Noctor, Estela M Muñoz Cellular Basis of Pineal Gland Development: Emerging Role of Microglia as Phenotype Regulator. PLoS ONE: 2016, 11(11);e0167063 PubMed 27861587
- Fumiyoshi Yamazaki, Morten Møller, Cong Fu, Samuel J Clokie, Artem Zykovich, Steven L Coon, David C Klein, Martin F Rath The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus. Brain Struct Funct: 2015, 220(3);1497-509 PubMed 24647753
- Russel J Reiter, Dun Xian Tan, Ahmet Korkmaz, Sergio A Rosales-Corral Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology. Hum. Reprod. Update: 2013, 20(2);293-307 PubMed 24132226
- Joice de Faria Poloni, Bruno César Feltes, Diego Bonatto Melatonin as a central molecule connecting neural development and calcium signaling. Funct. Integr. Genomics: 2011, 11(3);383-8 PubMed 21465271
- Morten Møller, Pansiri Phansuwan-Pujito, Corin Badiu Neuropeptide Y in the adult and fetal human pineal gland. Biomed Res Int: 2014, 2014;868567 PubMed 24757681 | PMC3976832 | Biomed Res Int.
- Morten Møller, Florian M M Baeres The anatomy and innervation of the mammalian pineal gland. Cell Tissue Res.: 2002, 309(1);139-50 PubMed 12111544
- Allisan Aquilina-Beck, Kristine Ilagan, Qin Liu, Jennifer O Liang Nodal signaling is required for closure of the anterior neural tube in zebrafish. BMC Dev. Biol.: 2007, 7;126 PubMed 17996054
- Martin F Rath, Kristian Rohde, David C Klein, Morten Møller Homeobox genes in the rodent pineal gland: roles in development and phenotype maintenance. Neurochem. Res.: 2013, 38(6);1100-12 PubMed 23076630
- Joshua A Clanton, Kyle D Hope, Joshua T Gamse Fgf signaling governs cell fate in the zebrafish pineal complex. Development: 2013, 140(2);323-32 PubMed 23250206
- Pineal Gland and Cancer-An Epigenetic Approach to the Control of Malignancy: Evaluation of the Role of Melatonin Eurekah Bioscience Collection - Neuropharmacology
- Endocrine changes in puberty Endocrinology -> The gonad
- Second Malignancies Cancer Medicine -> Section 24: The Eye -> 85. Neoplasms of the Eye -> Pediatric Ophthalmic Oncology: Ocular Diseases
- The Action of Melatonin on Experimental in-Vivo Tumors Eurekah Bioscience Collection -> Neuropharmacology -> Pineal Gland and Cancer-An Epigenetic Approach to the Control of Malignancy: Evaluation of the Role of Melatonin -> Effect of Melatonin on Tumor Growth
- Potential Significance of (Patho)Physiological Changes of Melatonin for the Aetiology of Cancer Eurekah Bioscience Collection -> Neuropharmacology -> Pineal Gland and Cancer-An Epigenetic Approach to the Control of Malignancy: Evaluation of the Role of Melatonin
- Effects of Exogenous Melatonin AHRQ Evidence reports and summaries -> AHRQ Evidence Reports, Numbers 61 - 119 -> 108. Mel
- Journal of Pineal Research Molecular, Biological, Physiological and Clinical Aspects of Melatonin
Dietmar Weinert Ontogenetic development of the mammalian circadian system. Chronobiol. Int.: 2005, 22(2);179-205 PubMed 16021838
M Mila Macchi, Jeffrey N Bruce Human pineal physiology and functional significance of melatonin. Front Neuroendocrinol: 2004, 25(3-4);177-95 PubMed 15589268
J Barrenetxe, P Delagrange, J A Martínez Physiological and metabolic functions of melatonin. J. Physiol. Biochem.: 2004, 60(1);61-72 PubMed 15352385
Peter Ekström, Hilmar Meissl Evolution of photosensory pineal organs in new light: the fate of neuroendocrine photoreceptors. Philos. Trans. R. Soc. Lond., B, Biol. Sci.: 2003, 358(1438);1679-700 PubMed 14561326
L Thomas, J E Drew, D R Abramovich, L M Williams The role of melatonin in the human fetus (review). Int. J. Mol. Med.: 1998, 1(3);539-43 PubMed 9852259
Bo Sun, Dan Wang, Yuchun Tang, Lingzhong Fan, Xiangtao Lin, Taifei Yu, Hengtao Qi, Zhenping Li, Shuwei Liu The pineal volume: a three-dimensional volumetric study in healthy young adults using 3.0 T MR data. Int. J. Dev. Neurosci.: 2009, 27(7);655-60 PubMed 19665543
S M Al-Hussain The pinealocytes of the human pineal gland: A light and electron microscopic study. Folia Morphol. (Warsz): 2006, 65(3);181-7 PubMed 16988913
Shin Saito, Tetsuya Tachibana, Yang-Ho Choi, D Michael Denbow, Mitsuhiro Furuse ICV melatonin reduces acute stress responses in neonatal chicks. Behav. Brain Res.: 2005, 165(2);197-203 PubMed 16182388
M Sumida, A J Barkovich, T H Newton Development of the pineal gland: measurement with MR. AJNR Am J Neuroradiol: 1996, 17(2);233-6 PubMed 8938291
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- NIH The Julius Axelrod Papers | The Pineal Gland and the "Melatonin Hypothesis," 1959-1974
- NIH Child Health and Human Development (USA) Pineal Gland and Chronobiology: Regulation of Pineal Function
- University of Cincinnati SURVEY OF ENDOCRINE ORGANS
- Cooper1932-fig01.jpg File:Cooper1932-fig02.jpg
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