HORMONES TIGHTLY COUPLED WITH SLEEP
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FIGURE 8
The secretion of prolactin rises during sleep, beginning about 30 to 90 minutes after the onset of sleep (Figure 8). Maximal levels are reached in the early morning. As with growth hormone, prolactin release is linked to sleep (although its secretion is independent of growth hormone secretion). For example, prolactin is released during afternoon naps; if sleep is delayed, prolactin release is delayed until sleep occurs. The level of prolactin secretion increases greatly during pregnancy, and the sleep-related release is maintained. The link between prolactin release and sleep is present from puberty until old age.
Thyroid stimulating hormone (thyrotropin) release has a much different relationship to sleep. This hormone reaches a peak each day in the evening and then declines across the sleep period.
In pubertal children and those approaching puberty, the release of gonadotropins, luteinizing hormone and follicle-stimulating hormone occurs during sleep. Luteinizing hormone release occurs at sleep onset and is inhibited during wakefulness. This sleep-related release of luteinizing hormone is the first sign of puberty and is thought by some to be the event that initiates puberty. The pubertal release of follicle-stimulating hormone also occurs during sleep and is inhibited during wakefulness. Studies in which the sleep period has been reversed have shown that the pubertal release of gonadotropins follows sleep and therefore is directly linked to sleep. In adults, the sleep-related nature of luteinizing hormone release is no longer present, although testosterone levels in males continue to be highest during sleep. In elderly males, this sleep-related pattern of testosterone release is no longer present.
Normally, the highest levels of plasma cortisol occur toward the end of sleep or just after waking up. When cortisol levels have been examined under various conditions in which the timing of sleep has been varied, it is also clear that sleep onset, regardless of its time, has an inhibitory effect on cortisol release. Thus, sleep can modulate the ongoing pattern of cortisol release.
Melatonin release from the pineal gland follows a circadian rhythm that is influenced by light and not by sleep (See Part VII, Temporal Regulation of Sleep and Wakefulness). The release of melatonin occurs during the night in humans, as well as in mammals that are active at night. Sleep neither potentiates melatonin release in the daytime nor does wakefulness inhibit melatonin release at night. Nocturnal melatonin release is inhibited by light. Melatonin release patterns adjust slowly, taking 10-12 days to reverse to a change in a light/dark schedule.
Receptors for melatonin have been localized to the suprachiasmatic nucleus of the hypothalamus, which is strongly implicated as the mammalian circadian pacemaker, and melatonin is thought to function in part as an hormonal transducer of the light/dark signal (see Part VII, Temporal Regulation of Sleep and Wakefulness). Seasonal information provided by this system has apparently significant interactions with reproductive activity in many mammals, although no similar function for melatonin has been found in humans. Scientists have recently shown that melatonin administration may produce drowsiness and has minor effects on human sleep, though there is no evidence that endogenous melatonin release is involved in sleep processes.
Renal Activity. Many sleep-related changes affect kidney function. These include a sleep-related increase in plasma aldosterone levels; an increase in prolactin secretion (described above), which some consider to potentiate the action of aldosterone. There is increased parathyroid hormone release during sleep, which may affect calcium excretion. In general, the following are reduced during sleep: glomerular filtration rate, renal plasma flow, filtration fraction, and the excretion of sodium, chloride, potassium, and calcium. Smaller quantities of more concentrated urine are excreted during NREM sleep than during wakefulness; during REM sleep urine excretion is reduced and concentrated to a greater extent than during NREM sleep.
Alimentary Activity. A number of interesting relationships between sleep and the digestive system have been reported. In individuals with a normal digestive system, gastric acid secretion decreases during sleep; but for those with active duodenal ulcers, there is an increase in gastric acid secretion - three to twenty times normal - during sleep. This elevated secretion is not related to a specific sleep stage or sleep state. Swallowing occurs with lower frequency during sleep than when awake, and the motility of the esophagus is also reduced.
Sexual Activity. Activation of the coïtusual organs during sleep is a commonplace occurrence in both males and females. In women, vaginal blood flow has been measured with a thermoconductance flow meter. In men, the most common measurement technique involves placing two small elastic circular mercury-filled capillary strain gauges around the penis, one at the base and one at the tip. The strain gauges measure the changes in penile diameter that occur with tumescence. Both types of measures are recorded on a polysomnograph along with EEG, EOG, and EMG activity. By this means changes in vaginal blood flow or in penile circumference can be correlated with the different stages of sleep and wakefulness.
Studies in normal males from 3 to 79 years of age have shown that REM sleep-related penile tumescence occurs in all normal, healthy males. Episodes of tumescence are clearly associated with REM sleep periods, although tumescence is not exclusively confined to REM sleep, particularly in adolescents (Figure 9). The peak period of tumescence time as a percentage of REM sleep time occurs in the mid-teens. The few studies that have been performed in females have found a similar relationship between coïtusual arousal and REM sleep, although the link between coïtusual arousal and REM sleep does not appear to be as strong as in males.
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FIGURE 9
Nocturnal penile tumescence cycle in a normal young man, showing five REM periods and associated maximum erections. Top graph shows EEG stages plotted against time (nine hours). Bottom graph shows penile circumference measured by strain gauge (SG). Full erection, 3 cm. Total REM time, 2-1/4 hours or 25% of total sleep time.
Among the earliest studies of penile tumescence during sleep were those attempting to relate tumescence to dream content. However, tumescence was found to occur in conjunction with REM sleep whether or not the dream content was coïtusual in nature.
There is some evidence that the occurrence of ejaculation during REM sleep (wet dreams) is more likely to occur if there is coïtusual content in the accompanying dream. In dreams in which anxiety, aggression, or rejection are prominent emotional phenomena, the accompanying tumescence shows very small, short-lived reductions in circumference.
The most common use of tests for nocturnal penile tumescence is to differentiate between organic impotence and impotence that is of psychogenic origin. For example, a male who is unable to have an erection during wakefulness for psychological reasons will have normal periods of tumescence during REM sleep. If tumescent episodes are not present during REM sleep, one would conclude that the impotence was of an organic nature. It should also be pointed out that few diagnostic tools are entirely accurate, for there are some recent data that nocturnal penile tumescence may also decrease in depression.
Thermoregulation Body temperature is regulated during NREM sleep at a lower set point. Therefore, temperature is kept at a lower level than during wakefulness. Shivering is also initiated at a lower temperature during NREM sleep than during wakefulness. Further, sweating will occur during NREM sleep when the ambient temperature is high or even in the waking thermoneutral range. Thus, although the ambient temperature may feel very comfortable when you go to bed, you may wake up later sweating.
Body temperature is not regulated during REM sleep. Therefore, shivering in response to a cold temperature stops during REM sleep as does sweating in response to a hot temperature. As a consequence, for as long as REM sleep persists, one's body temperature will drift toward the environmental temperature. In extremes of environmental temperatures sleep becomes disrupted; REM sleep is then reduced much more than NREM sleep, so that body temperature usually continues to be actively regulated. Newborn human infants may be at particular risk for catastrophic thermal events during sleep because they have such a large amount of REM sleep and because the drive to maintain REM sleep is so very great in infants.
Mammals and birds are ambient endotherms , and the cost in energy expenditure to maintain body temperature is great. It has been estimated that the metabolic rate of endotherms is 8 to 10 times that of reptiles of a similar size when they are passively heated to the same body temperature. Although there are clear state-related changes in thermoregulation, one must also keep in mind that one of the basic underlying body rhythms is the daily rhythm of core body temperature (Figure 10). This circadian rhythm will be described more fully in Part G., Temporal Regulation of Sleep and Wakefulness, but it is relevant to note that although a daily temperature pattern persists even in the absence of sleep, it does correlate with cycles of alertness. Thus, the state-dependent regulation of temperature involves control mechanisms independent from those responsible for the circadian pattern of sleep.
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FIGURE 10
Average subjective alertness and body temperature of 15 subjects experiencing 72 hours of sleep deprivation under temporal isolation.
Infection. During systemic infections, people often experience increased lassitude or sleepiness. Unfortunately, studies of the relationship of infection to sleep have not been performed in humans. The sleepiness associated with hepatic failure may be relieved in seconds by the administration of benzodiazepine receptor antagonists. In experimental animals, initial work in this area indicates that: 1) very large changes in sleep patterns occur during infection; 2) sleep changes are a major sign of infectious disease; and 3) sleep changes are adaptive and possibly play a role in nonspecific host defenses. (A contrary note is that prolonged sleep deprivation does not reduce any of several measures of immune response). The general pattern after bacterial or fungal infection is an initial period of enhanced NREM sleep, followed 1-2 days later by a period of suppressed NREM. REM sleep is inhibited throughout the course of infection. It is clear that during infection and illness there is an increased tendency to sleep; it is suspected, but not proven, that sleep facilitates the healing process.
