UNSW Embryology

Endocrine Development - Pineal

© Dr Mark Hill (2008)

Acknowledgements

Introduction

The pineal gland (epiphysis cerebri) has an important role in the sleep/wake daily cycle and reproductive development.

In humans, the postnatal 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. (More? Kennaway DJ, etal, 1996)

In other species, it has been shown that 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.

Pineal Gland (adult hindbrain and midbrain, postero-lateral view)

The pineal gland is located at the base of the brain and cells called pinealocytes manufactures the lipophilic hormone melatonin, derivative of the amino acid tryptophan.

Melatonin synthesis and levels in the blood rises and falls on a circadian (daily) cycle, levels can be detected by the presence of a metabolite in the urine. (More? melatonin)

Page Links: Introduction | Some Recent Findings | Melatonin | Histology | Reading | Development Overview |Abnormalities | Molecular Development | Genes | WWW Links | References | Glossary

Some Recent Findings

Weinert D.    [See Related Articles] Ontogenetic development of the mammalian circadian system. Chronobiol Int. 2005;22(2):179-205.

"This review summarizes the current knowledge about the ontogenetic development of the circadian system in mammals. The developmental changes of overt rhythms are discussed, although the main focus of the review is the underlying neuronal and molecular mechanisms."

Reading

Human Embryology (2nd ed.) Larson The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud Ch10: p230-233, Ch12: p280-282, Ch13: p319-347 Before We Are Born (5th ed.) Moore and Persaud Essentials of Human Embryology Larson Human Embryology Fitzgerald and Fitzgerald Ch24: p166-167 Search PubMed- Medline

Objectives

• Understand the main steps in the development of the thyroid, parathyroid, adrenal, pituitary, pineal glands, thymus and gonads.
• Have a general understanding of the chief functions of these endocrine organs.
• Understand the endocrine contribution to embryo development.
• Have a general understanding of different types of hormones and their signaling actions.

Computer Activities

UNSW Embryology: Stage 13/14 Embryo | Stage 22 Embryo | Selected Sections Stage 22 Embryo | Abnormal Endocrine Development

Embryo Images Unit: Brain (Weeks 9-15)

Development Overview

Pineal Site of synthesis of melatonin, light sensitive in lower vertebrates (lost evolutionarily)

Embryonic appears as a diverticulum in the diencephalic roof of the third ventricle.

Birth - no melatonin cycle present.

Postnatal (8 to 15 weeks, 49 to 55 weeks postconception) - melatonin cycle present as detected by rhythmic urinary metabolite excretion.

Postnatal (3 to 5 years) - peak melatonin concentrations.

Melatonin

Melatonin is synthesized from the amino acid tryptophan within the pinealocytes.

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.

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.

Melatonin levels can be monitored by urinary excretion of the melatonin metabolite 6-sulfatoxymelatonin (aMT.6S).

Histology

The pineal gland has a very interesting histological structure based upon its unique anatomical position.

Pineal gland (sheep, H&E) Pinealocytes and the astrocytes have long processes, this gives the "stringy" histological appearance. UWA Blue Histology - Pineal (Image: Lutz Slomianka, UWA Blue Histology)

Now look at the slides from UNSW Virtual Slidebox BGD (B) Histology of the HP Axis.

Links: UWA Blue Histology - Pineal | Virtual Slide - Endocrine |

Abnormalities

Pineal Hypoplasia associated with retinal disease.

Pineal Tumours in children are associated with abnormal puberty development.

WWWLinks

NIH Child Health and Human Development (USA) Pineal Gland and Chronobiology: Regulation of Pineal Function

University of Cincinnati SURVEY OF ENDOCRINE ORGANS

Molecular Development

DARPP-32 (Dopamine- and cAMP-regulated phosphoprotein of 32 kDa) is involved in the retinal pathway transmitting photic information that resets the circadian clock.

References

Links: Reviews | Articles | Online Textbooks | Search Textbooks | Search PubMed | Glossary

PubMed

• Weinert D.    [See Related Articles] Ontogenetic development of the mammalian circadian system. Chronobiol Int. 2005;22(2):179-205.
• Macchi MM, Bruce JN.    [See Related Articles] Human pineal physiology and functional significance of melatonin. Front Neuroendocrinol. 2004 Sep-Dec;25(3-4):177-95.
• Barrenetxe J, Delagrange P, Martinez JA.    [See Related Articles] Physiological and metabolic functions of melatonin. J Physiol Biochem. 2004 Mar;60(1):61-72.
• Ekstrom P, Meissl H.    [See Related Articles] Evolution of photosensory pineal organs in new light: the fate of neuroendocrine photoreceptors. Philos Trans R Soc Lond B Biol Sci. 2003 Oct 29;358(1438):1679-700.
• Thomas L, Drew JE, Abramovich DR, Williams LM.    [See Related Articles] The role of melatonin in the human fetus (review). Int J Mol Med. 1998 Mar;1(3):539-43.

Articles

• Saito S, Tachibana T, Choi YH, Denbow DM, Furuse M.    [See Related Articles] ICV melatonin reduces acute stress responses in neonatal chicks. Behav Brain Res. 2005 Dec 7;165(2):197-203.
• Kennaway DJ, Goble FC, Stamp GE.    [See Related Articles] Factors influencing the development of melatonin rhythmicity in humans. J Clin Endocrinol Metab. 1996 Apr;81(4):1525-32.

Search PubMed

Search Feb 2006 "pineal development" 1178 reference articles of which 167 were reviews.

Search PubMed: term = pineal development

Online Textbooks

• 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

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