Endocrine - Pineal Development
|Embryology - 27 Mar 2017 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.
Constantin Virgil Gîngu, Mihaela Mihai, Cătălin Baston, Mugurel Alexandru Crăsneanu, Alexandru Vladimir Dick, Vlad Olaru, Ioanel Sinescu
Primary retroperitoneal seminoma - embryology, histopathology and treatment particularities.
Rom J Morphol Embryol: 2016, 57(3);1045-1050
- 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
- 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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|Embryology History | Historic Embryology Papers)|
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
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
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
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
Morten Møller, Pansiri Phansuwan-Pujito, Corin Badiu
Neuropeptide Y in the adult and fetal human pineal gland.
Biomed Res Int: 2014, 2014;868567
Morten Møller, Florian M M Baeres
The anatomy and innervation of the mammalian pineal gland.
Cell Tissue Res.: 2002, 309(1);139-50
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
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
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
- 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
Ontogenetic development of the mammalian circadian system.
Chronobiol. Int.: 2005, 22(2);179-205
M Mila Macchi, Jeffrey N Bruce
Human pineal physiology and functional significance of melatonin.
Front Neuroendocrinol: 2004, 25(3-4);177-95
J Barrenetxe, P Delagrange, J A Martínez
Physiological and metabolic functions of melatonin.
J. Physiol. Biochem.: 2004, 60(1);61-72
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
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
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
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
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
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
Search Pubmed: pineal development
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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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