Endocrine - Pineal Development

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Introduction

Developing pineal gland
Adult pineal body
Pineal gland position

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.[1]


Overview

  • 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?


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.

Endocrine Links: Introduction | BGD Lecture | Science Lecture | Pineal | Hypothalamus‎ | Pituitary | Thyroid | Parathyroid | Thymus‎ | Pancreas‎ | Adrenal‎ | Gonad‎ | Placenta‎ | Other Tissues | Stage 22 | Abnormalities | Hormones | Category:Endocrine
Historic Embryology - Endocrine  
1904 interstitial Cells | 1908 Pancreas Different Species | 1912 Suprarenal Bodies | 1914 Suprarenal Organs | 1915 Pharynx | 1916 Thyroid | 1918 Rabbit Hypophysis | 1935 Mammalian Hypophysis | 1926 Human Hypophysis | 1937 Pineal | 1938 Parathyroid | 1941 Thyroid | 1950 Thyroid Parathyroid Thymus
Lecture - Endocrine Development | Lecture - Head Development | 1937 Human Pineal | Category:Pineal

Some Recent Findings

  • The Lhx9 homeobox gene controls pineal gland development and prevents postnatal hydrocephalus[2] "Lhx9 is a member of the LIM homeobox gene family. It is expressed during mammalian embryogenesis in the brain including the pineal gland. Deletion of Lhx9 results in sterility due to failure of gonadal development. The current study was initiated to investigate Lhx9 biology in the pineal gland. Lhx9 is highly expressed in the developing pineal gland of the rat with transcript abundance peaking early in development; transcript levels decrease postnatally to nearly undetectable levels in the adult, a temporal pattern that is generally similar to that reported for Lhx9 expression in other brain regions. Studies with C57BL/6J Lhx9 (-/-) mutant mice revealed marked alterations in brain and pineal development. Specifically, the superficial pineal gland is hypoplastic, being reduced to a small cluster of pinealocytes surrounded by meningeal and vascular tissue. The deep pineal gland and the pineal stalk are also reduced in size. Although the brains of neonatal Lhx9 (-/-) mutant mice appear normal, severe hydrocephalus develops in about 70 % of the Lhx9 (-/-) mice at 5-8 weeks of age; these observations are the first to document that deletion of Lhx9 results in hydrocephalus and as such indicate that Lhx9 contributes to the maintenance of normal brain structure. Whereas hydrocephalus is absent in neonatal Lhx9 (-/-)mutant mice, the neonatal pineal gland in these animals is hypo plastic."
  • Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology[3] "A number of conclusions naturally evolve from the data summarized in this review: (i) melatonin, of both pineal and placental origin, has essential functions in fetal maturation and placenta/uterine homeostasis; (ii) circadian clock genes, which are components of all cells including those in the peripheral reproductive organs, have important roles in reproductive and organismal (fetal and maternal) physiology; (iii) due to the potent antioxidant actions of melatonin, coupled with its virtual absence of toxicity, this indoleamine may have utility in the treatment of pre-eclampsia, intrauterine growth restriction, placental and fetal ischemia/reperfusion, etc. (iv) the propensity for parturition to occur at night may relate to the synergism between the nocturnal increase in melatonin and oxytocin."
  • Melatonin as a central molecule connecting neural development and calcium signaling[4] "Melatonin (MEL) is a neuroendocrine hormone secreted by the pineal gland in association with the suprachiasmatic nucleus and peripheral tissues. MEL has been observed to play a critical role in the reproductive process and in the fetomaternal interface. Extrapineal synthesis has been reported in mammalian models during pregnancy, especially by the placenta tissue."
More recent papers  
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This table shows an automated computer PubMed search using the listed sub-heading term.

  • Therefore the list of references do not reflect any editorial selection of material based on content or relevance.
  • References appear in this list based upon the date of the actual page viewing.

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.

Links: References | Discussion Page | Pubmed Most Recent | Journal Searches


Search term: Pineal Embryology


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


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


Iwona Adamska, Bogdan Lewczuk, Magdalena Markowska, Pawel M Majewski
Daily profiles of melatonin synthesis-related indoles in the pineal glands of young chickens (Gallus gallus domesticus L.).
J. Photochem. Photobiol. B, Biol.: 2016, 164;335-343


B Gençer Tarakçı, A Girgin, S Timurkaan, M H Yalçın, F M Gür, M Karan
Immunohistochemical localization of irisin in skin, eye, and thyroid and pineal glands of the crested porcupine (Hystrix cristata).
Biotech Histochem: 2016, 91(6);423-7


Xueran Chen, Aijun Hao, Xian Li, Zhaoxia Du, Hao Li, Hongzhi Wang, Haoran Yang, Zhiyou Fang
Melatonin inhibits tumorigenicity of glioblastoma stem-like cells via the AKT-EZH2-STAT3 signaling axis.
J. Pineal Res.: 2016, 61(2);208-17

Development Overview

  • 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[5]

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.

Fetal pineal gland 01.jpg

Melatonin

Melatonin molecular structure
  • 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).

Melatonin Receptors

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.
Links: Image - melatonergic receptors coupled via Gαi

Innervation

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.[6]

  • 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


Molecular Development

  • Nodal - zebrafish required for dorsal convergence of pineal precursors.[7]
  • Pax6 - rat pineal gland from E16, peak expression around E18.[8]
  • Fgf8a - zebrafish epithalamus acts permissively to promote parapineal fate.[9]
  • 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

Abnormalities

  • Pineal Hypoplasia associated with retinal disease.
  • Pineal Tumours in children are associated with abnormal puberty development.

Histology

Adult Pineal (sheep)

Adult Histology

  • 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

Images

Historic

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Pages where the terms "Historic Textbook" and "Historic Embryology" appear on this site, and sections within pages where this disclaimer appears, indicate that the content and scientific understanding are specific to the time of publication. This means that while some scientific descriptions are still accurate, the terminology and interpretation of the developmental mechanisms reflect the understanding at the time of original publication and those of the preceding periods, these terms and interpretations may not reflect our current scientific understanding.     (More? Embryology History | Historic Embryology Papers)

Cooper, ERA. The Human Pineal Gland and Pineal Cysts (1932)

Cooper1932-fig01.jpg Cooper1932-fig02.jpg
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.

References


  1. 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


  2. 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


  3. 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


  4. 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


  5. Morten Møller, Pansiri Phansuwan-Pujito, Corin Badiu
    Neuropeptide Y in the adult and fetal human pineal gland.
    Biomed Res Int: 2014, 2014;868567

    | PMC3976832 | Biomed Res Int.


  6. Morten Møller, Florian M M Baeres
    The anatomy and innervation of the mammalian pineal gland.
    Cell Tissue Res.: 2002, 309(1);139-50


  7. 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


  8. 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


  9. 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


Online Textbooks

Journals

Reviews


Dietmar Weinert
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

Articles


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

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Cite this page: Hill, M.A. 2017 Embryology Endocrine - Pineal Development. Retrieved March 27, 2017, from https://embryology.med.unsw.edu.au/embryology/index.php/Endocrine_-_Pineal_Development

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