Biology of Disease

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The pineal gland or body is an appendage of the posterior end

of the roof of the third ventricle in the brain (Figure 7.4). It is

shaped like a pinecone, hence its name, weighs 100 to 150

mg and is only 8 to 10 mm long. It is composed largely of

pinealocytes and glial cells. In older animals, the pineal often

contains calcium deposits, sometimes referred to as brain sand!

Descartes (1596–1650) regarded the pineal gland as ‘the seat

of the soul’, because he believed it was unique in the human

brain in being the only structure not duplicated on the right and

left sides. This observation is not strictly true, however, since it is

finely divided into two hemispheres that can be observed with

a microscope.

The physiological function of the pineal gland in humans is

poorly understood. However, pinealocytes are known to produce

the hormone, melatonin (5-methoxy-N-acetyltryptamine), from

tryptophan by acetylating serotonin (Figure 7.5). Melatonin has

a relatively simple structure yet communicates information about

environmental lighting to physiological systems of the body. This

light-transducing ability has led some to call the pineal gland

the ‘third eye’. Melatonin, therefore, helps regulate the internal

‘clock’ of the body affecting biological rhythms and, in particular,

patterns of sleeping and waking and possibly the onset of

puberty. It may also function as a free radical scavenger and

reduce oxidative damage. Most melatonin is synthesized during

the night and can be secreted directly into the blood because the

capillaries of the pineal gland are permeable and do not form

part of the normal blood–brain barrier (Figure 3.4). In a normal

environment in healthy humans the release of melatonin usually

starts at 21.00 to 22.00 h and ends between 07.00 to 09.00 h,

with peak levels of 60 to 70 pg cm–3occurring in the plasma of

adults between 02.00 and 04.00 h. The activity of the usual rate-

limiting enzyme, serotonin-N-acetyltransferase (NAT), increases

7–150 fold during peak production. In daylight the activity of

NAT, and therefore melatonin production, is reduced. The rhythm

is endogenously synchronized to 24 h by the suprachiasmatic

nucleus of the hypothalamus, an area of the brain known to

coordinate biological clock signals, but can be entrained to values

between 23 and 27 h primarily by the environmental light–dark

cycle acting through the retina. When the retina is exposed

to light, nervous impulses are relayed to the suprachiasmatic

nucleus. Nerve fibers from the hypothalamus descend to the

spinal cord, from where postganglionic fibers ascend back to

the pineal gland. Thus the pineal gland can measure day length

and adjust its secretion of melatonin appropriately.

Small cysts are commonly seen within the pineal region

although their discovery is frequently incidental to radiographic

investigations. However, they are benign and nonprogressive and

should be treated conservatively. The pineal gland is also subject

to numerous types of malignant tumors, for example teratomas,

germinomas, choriocarcinomas, endodermal sinus tumors,

mixed germ cell tumors, pineoblastoma and pineocytoma,

and gliomas. Fortunately, all are rare and collectively account

for less than 1% of intracranial space-occupying lesions. With

the exception of parenchymal cell tumors, pineoblastoma and

pineocytoma, they occur mainly in patients below the age of 20

years. Germinomas and teratomas occur predominantly in males.

The commonest symptoms are secondary to hydrocephalus,

such as headaches, vomiting, and drowsiness, with visual

problems, diabetes insipidus, and reproductive abnormalities. In

children, pineal tumors of the region are often associated with

abnormal pubertal development. Some evidence suggests that

precocious puberty is due to the production of human chorionic

gonadotrophin (hCG) by germ cell tumors of the pineal gland.

Delayed puberty has also been associated with pineal tumors.

BOX 7.1 The pineal gland

Pineal gland

Cerebellum

Hypothalamus

Pituitary gland Brain

stem

Cerebrum

Figure 7.4 Schematic showing the location and

structure of the pineal gland.