The small, cone-shaped pineal gland is located in the roof of the third ventricle of the diencephalon (chapter 8), where it is encapsulated by the meninges covering the brain. The pineal gland of a child weighs about 0.2 g and is 5 to 8 mm (0.2 to 0.3 in.) long and 9 mm wide. The gland begins to regress in size at about age 7 and in the adult appears as a thickened strand of fibrous tissue. Although the pineal gland lacks direct nervous connections to the rest of the brain, it is highly innervated by the sympathetic nervous system from the superior cervical ganglion.
The principal hormone of the pineal gland is melatonin. Production and secretion of this hormone is stimulated by activity of the suprachiasmatic nucleus (SCN) in the hypothalamus of the brain via activation of sympathetic neurons to the pineal gland (fig. 11.32). The SCN is the primary center for circadian rhythms in the body: rhythms of physiological activity that follow a 24hour pattern. The circadian activity of the SCN is automatic, but environmental light/dark changes are required to entrain (synchronize) this activity to a day/night cycle. Activity of the SCN, and thus secretion of melatonin, begins to increase with darkness and peaks by the middle of the night. During the day, neural pathways
Chapter Eleven from the retina of the eyes to the hypothalamus (fig. 11.32) act to depress the activity of the SCN, reducing sympathetic stimulation of the pineal and thus decreasing melatonin secretion.
The pineal gland has been implicated in a variety of physiological processes. One of the most widely studied is the ability of melatonin to inhibit the pituitary-gonad axis (inhibiting GnRH secretion or the response of the anterior pituitary to GnRH, depending on the species of animal). Indeed, a decrease in melatonin secretion in many species is required for the maturation of the go-nads during the reproductive season of seasonal breeders. Although there is evidence to support an antigonadotropic effect in humans, this possibility has not yet been proven. For example, excessive melatonin secretion in humans is associated with a delay in the onset of puberty. Research findings indicate that melatonin secretion is highest in children between the ages of 1 and 5 and decreases thereafter, reaching its lowest levels at the end of puberty, when concentrations are 75% lower than during early childhood. This suggests a role for melatonin in the onset of human puberty. However, because of much conflicting data, the importance of melatonin in human reproduction is still highly controversial.
The pattern of melatonin secretion is altered when a person works night shifts or flies across different time zones. There
■ Figure 11.32 The secretion of melatonin. The secretion of melatonin by the pineal gland is stimulated by sympathetic axons originating in the superior cervical ganglion. Activity of these neurons is regulated by the cyclic activity of the suprachiasmatic nucleus of the hypothalamus, which sets a circadian rhythm. This rhythm is entrained to light/dark cycles by neurons in the retina.
is evidence that exogenous melatonin (taken as a pill) may be beneficial in the treatment of jet lag, but the optimum dosage is not currently known. Phototherapy using bright fluorescent lamps, which act like sunlight to inhibit melatonin secretion, has been used effectively in the treatment of seasonal affective disorder (SAD), or "winter depression."
Melatonin pills decrease the time required to fall asleep and increase the duration of rapid eye movement (REM) sleep; for these reasons, they may be useful in the treatment of insomnia. This is particularly significant for elderly people with insomnia, who have the lowest nighttime levels of endogenous melatonin secretion. Melatonin can also act, much like vitamin E, as a scavenger of hydroxyl and other free radicals that can cause oxidative damage to cells. This antioxi-dant effect of melatonin, however, only occurs at pharmacological, rather than at normal physiological, doses. The purported beneficial effects of exogenous melatonin (other than for insomnia and jet lag) are not yet proven, and the consensus of current medical opinion is against the uncontrolled use of melatonin pills.
■ Figure 11.33 The thymus is a bilobed organ within the mediastinum of the thorax. The thymus secretes hormones that help to regulate the immune system.
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