Difference between revisions of "Endocrine - Pineal Development"

From Embryology
Line 46: Line 46:
* caudal roof, median diverticulum, epiphysis
* caudal roof, median diverticulum, epiphysis
* Initially a hollow diverticulum, cell proliferation to solid, pinealocytes (neuroglia), cone-shaped gland innervated by epithalamus
* 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
[[Neural - Epithalamus Development|'''Epithalamus''']] consists of the pineal gland and habenular nuclei
| Fetal Pineal Anatomy<ref name = PMID24757681><pubmed>24757681</pubmed>| [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976832 PMC3976832] | [http://www.hindawi.com/journals/bmri/2014/868567 Biomed Res Int.]</ref>
| Fetal Pineal Anatomy<ref name = PMID24757681><pubmed>24757681</pubmed>| [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976832 PMC3976832] | [http://www.hindawi.com/journals/bmri/2014/868567 Biomed Res Int.]</ref>

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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]

In Brief

  • 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 | Lecture Movie | pineal | hypothalamus‎ | pituitary | thyroid | parathyroid | thymus | pancreas | adrenal | endocrine gonad‎ | endocrine placenta | other tissues | Stage 22 | endocrine abnormalities | Hormones | Category:Endocrine
Historic Embryology - Endocrine  
1903 Islets of Langerhans | 1903 Pig Adrenal | 1904 interstitial Cells | 1908 Pancreas Different Species | 1908 Pituitary | 1908 Pituitary histology | 1911 Rathke's pouch | 1912 Suprarenal Bodies | 1914 Suprarenal Organs | 1915 Pharynx | 1916 Thyroid | 1918 Rabbit Hypophysis | 1920 Adrenal | 1935 Mammalian Hypophysis | 1926 Human Hypophysis | 1927 Adrenal | 1927 Hypophyseal fossa | 1930 Adrenal | 1932 Pineal Gland and Cysts | 1935 Hypophysis | 1935 Pineal | 1937 Pineal | 1935 Parathyroid | 1940 Adrenal | 1941 Thyroid | 1950 Thyroid Parathyroid Thymus | 1957 Adrenal

| Lecture - Endocrine Development | Lecture - Head Development | 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."
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Search term: Pineal Embryology

<pubmed limit=5>Pineal Embryology</pubmed>

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 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


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


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


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


  1. <pubmed>8636362</pubmed>
  2. <pubmed>24647753</pubmed>
  3. <pubmed>24132226</pubmed>
  4. <pubmed>21465271</pubmed>
  5. <pubmed>24757681</pubmed>| PMC3976832 | Biomed Res Int.
  6. <pubmed>12111544</pubmed>
  7. <pubmed>17996054</pubmed>
  8. <pubmed>23076630</pubmed>
  9. <pubmed>23250206</pubmed>

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Cite this page: Hill, M.A. (2021, May 15) Embryology Endocrine - Pineal Development. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Endocrine_-_Pineal_Development

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