Circadian Hormonal Rhythms example essay topic

"Physiology of Endocrine Rhythms and the Role of the Pineal Gland In Determine Circadian Rhythms" Endocrine Rhythms Many hormones are not secreted in a continuous fashion, but show fluctuations that are rhythmic. The regularity of these hormone rhythms is very important for homeostasis. Hormone rhythms are the regular patterns in which the levels of different hormones fluctuate in the body. Some hormone rhythms show high and low peaks occurring every few minutes or hours. Other hormones fluctuate over a 24-hour cycle and are called diurnal rhythms.

Circadian hormonal rhythms also fluctuate over a 24 hour cycle, but are intrinsic rhythms which persist even in the absence of environmental cues such as sleep-wake state, the light-dark cycle, meals, exercise or body position. Finally, there are hormones, such as those of the menstrual cycle, that are secreted on a monthly basis. Circadian Rhythm The word circadian comes from the Latin root circa nia meaning circle. For modern purposes, the word circadian refers to anything that occurs in 24 cycles or periods. "Rest and activity, taking in of fluid, formation of urine, body temperature, cardiac output, oxygen consumption, cell division, and the secreting activity of endocrine glands" all participate in 24-hour cycles in many organisms, and are referred to as circadian rhythms. One of the most well understood circadian rhythms is the sleep circadian rhythm.

The circadian rhythm, commonly known as the biological clock, is thought to have three components, including the genetic machinery that allows the clock to regulate the expression of specific genes, the timekeeping machinery of the clock, and receptors that collect input from the outside world to set the clock. Melatonin, the primary product of the pineal gland, has been known to regulate sleep cycles during the night for some time now. Just recently, scientists have discovered melatonin daytime counterpart SAM. SAM, a derivative of the amino acid methionine, combines with serotonin to make melatonin. SAM is manufactured to relatively high concentrations during the day, and burned away to low concentrations in the night. Serotonin also goes through a slight concentration drop in the night due to its role in melatonin formation, but, because it is needed in many other essential parts of the brain, its concentration does not vary as much as melatonin and SAM.

The molecular circadian cycle of the three molecules can be seen in graphical form below. Molecular Cycles in the Sleep Circadian Rhythm Encarta (c) 1999 The graph on the left shows how alertness varies through out the day in relation to the three circadian phase regulatory molecules. Serotonin and SAM both start off in relatively high concentrations in the height of the day, while melatonin is almost nowhere to be found. As the sun begins to set, the pineal gland recognizes that there is less and less light. Norepinephrine begins to bind to ^a-receptors in the pineal gland, and the pineal gland used the day time store of SAM and serotonin to manufacture melatonin Understandably, while melatonin concentrations rise, SAM and serotonin concentrations fall.

Once the concentration of SAM is too low to make any more melatonin, melatonin levels start to drop off, and SAM is free to rebuild. When the pineal gland senses the coming of light, SAM is produced again starting a new daily cycle. By observing the two graphs, you can see that high melatonin levels correspond to feelings of sleepiness, while high serotonin and SAM levels correspond to high levels of alertness. As of May 2000, nine genes had been found that regulate circadian rhythms in mammals. Eight of the genes were found to be transcription factors, and the ninth gene encoded a kinase enzyme.

Researchers discovered that a single amino acid mutation in the kinase, casein kinase I epsilon (CHI), rendered it slower to phosphorylase and turn on a group of proteins encoded by the gene located at the tao locus named period. When this gene was inserted into hamsters, their circadian rhythms were shortened from 24 to 20 hours, thus demonstrating that timekeeping proteins do exist. Another study, done by Rosbash and Hall, discovered the that crypto chromes found in almost all organisms, including human retina, absorb blue light and send signals that reset many kinds of circadian rhythms to the day night cycle. This was significant, because it was thought that the same rods and cones that were used for sight somehow transmitted signals to the brain that told when night was coming. Rosbash and Hall proved that there was a totally separate system of nerves and receptors dedicated to the biological clock that were pretty much universal through out the animal kingdom, and these light receptors appear to be located through out the body, not just in the eyes. Pineal Gland The pineal gland is a small gland, about the size of a grain of rice, located in the cerebrum.

Because the pineal gland is located near the eyes, it is shaped like an eye, and it is sensitive to light, especially in some reptiles, the pineal gland is thought to be the evolutionary precursor to the eyes. We now know that the pineal gland is important in keeping the mammalian biological clock. Upon the removal of light, the sympathetic nervous system hormone, norepinephrine, activates the pineal gland to produce melatonin from serotonin and SAM. Even though an excitatory sympathetic hormone stimulates the pineal glands actions, the pineal gland soon causes sleepiness after exposure to norepinephrine. Researchers showed that the propensity to be an early riser is rooted in the time of day that the pineal gland releases the sleep hormone melatonin, and the time that it takes for the person to respond to the melatonin. They found that, in morning types, the pineal gland releases melatonin many hours before evening types with reliability, causing morning types to be less fit for nightly activities.

Since light on this planet is regulated alternatively day and night (circadian), it would be easy to discern the relation of such cycles to the pineal and other glands. There are 24-hour cycles in the concentrations of serotonin (N-acetyl serotonin - NAS) and melatonin in the pineal of the rat. There is also a 24-hour cycle in the conversion of the norepinephrine in the sympathetic nerves innervating in the pineal gland. "This rhythm persists in blinded rats and animals but is suppressed in normal rats by light.

The same rhythm in norepinephrine turnover generates the rhythms in pineal indole-amines and N-acetyltransferases". There is a relationship between sex hormones and the light receptive quality of the epiphysis. It has been proposed that one function of the pineal in the rat is to serve as a neuroendocrine transducer, mediating the effects of environmental lighting on the gonads. Accordingly information about lighting is perceived by the retina and nervous impulses are conveyed to the pineal gland by way of the sympathetic nerve.

The pineal responds by altering its production of methoxyindoles, these enter the bloodstream and influence endocrine economy of the body. The methoxyindoles are synthesized by the pineal in the absence of light and presumably exert inhibitory effects on the gonads. Another curious feature of the pineal organ is the production of melatonin and serotonin. Serotonin is produced in the gut of the intestinal tract as well as the Pineal organ. Serotonin is another transmitter. It is one of the major four neuro hormones.

Melatonin The interesting thing about serotonin is its change over to melatonin, which occurs chemically in the pineal gland. The pineal gland is the only area where this is done. This hypothetic scheme, suggests that under conditions of darkness, the pineal is stimulated to release melatonin, in the general circulation. Melatonin exerts a profound contracting effect on dermal melanophores (pigment pores) leading to rapid blanching. The involvement of the pineal in this response relates to two aspects of its physiology, light reception and endocrine function. Melatonin Synthesis Melatonin is synthesized within the pineal gland from tryptophan.

The secretion pattern is generated within the suprachiasmatic nucleus (SCN). Synthesis occurs upon exposure to darkness, with the increased activity of serotonin-N-acetyltransferases. By the action of hydroxy indole-O-methyltransferase (HI OMT), N-acetyl serotonin is converted to melatonin. Melatonin is then rapidly secreted into the vascular system and, possibly, into the cerebrospinal fluid. Peripheral tissues, such as the retina and the gut, are also known to synthesize melatonin. Melatonin is synthesized and secreted during the dark phase of the day.

The secretion rhythm is endogenous (internally generated), and generally persists in the absence of time cues, assuming a period that deviates only slightly from 24 hours. Thus, it is a true circadian rhythm. Melatonin secretion is related to the length of the night. The longer the night, the longer the duration of the secretion. If humans are kept strictly in darkness for 14 hours per day over a period of one month, the duration of melatonin secretion expands to cover almost the entire dark period. Conversely, if a subject is exposed to light for 14 hours per day, the duration of secretion shrinks to 10 hours, accompanied by concomitant changes in body temperature and sleep.

Light exposure of the retina alters the amount of serotonin metabolized to melatonin, via the neural pathways that connect the retina to the pineal gland. The individual's visual system must be intact for proper synchronization of the melatonin rhythm. Blind persons commonly exhibit a pronounced lack of circadian rhythm, with free-running cycles generated internally despite the presence of other external time cues in their environment. Other Circadian Hormones Some of the hormones influenced by the circadian system are growth hormone (GH), prolactin, thyrotropin, and testosterone. One endocrine event clearly under the influence of the clock is the release of the hormone ACTH. The SCN triggers the hypothalamus, which activates the anterior pituitary to release ACTH, causing the adrenal glands to release cortisol and aldosterone.

A plot of cortisol concentration in blood plasma shows a characteristic peak in the very early morning (around 6 AM) with a trough right before sleep. Similarly, aldosterone level is constantly high throughout the night and low throughout the day. Like all the other anterior pituitary hormones, PRL (Prolactin) is secreted episodically. The secretions are irregular in frequency, duration and amplitude due to large variety of factors that affect PRL secretion, though it is generally accepted that there may be 4 to 11 peaks per day, with slightly more frequent and higher peaks during sleep. The maximum PRL peak usually occurs about 5-7 a. m., however it is not a true circadian rhythm, but rather a nyctohemeral (sleep associated) rhythm as peaks are observed during naps at whatever time it is. ACTH regulates steroid synthesis by the Adrenal Cortex.

ACTH stimulates the secretion of cortisol from the adrenal glands. Cortisol and other glucocorticoid increase glucose production, inhibit protein synthesis and increase protein breakdown, stimulate lipolysis, and affect immunological and inflammatory responses. Cortisol induces thymus 'involution' which is a decline in normal thymus function that, in part accounts for its ability to decrease immune system response. Glucocorticoid helps maintain blood pressure and form an essential component of the body's response to stress. ACTH secretion is regulated by corticotropin- releasing hormone (CRH) and anti diuretic hormone (ADH).

Through negative feedback cortisol feeds back to the pituitary and hypothalamus to suppress levels of ACTH and CRH. Under basal (non-stress) conditions, cortisol is secreted with a pronounced circadian rhythm, with higher levels early in the morning and low levels late in the evening. Under stressful conditions, the circadian variation is stifled. When the clock goes out of whack. No clock is perfect, however. When organisms are deprived of the cues the world normally provides, they display a characteristic "free-running" period of not quite 24 hours.

As a result, free-running animals drift slowly out of phase with the natural world. In experiments in which people are isolated for long periods of time, they continue to eat and sleep on regular but increasingly out-of-phase schedules, although human body clocks do approximate the 24-hour cycle and not a 25-hour cycle as previously thought, and nor does this cycle decrease as people get older. Such drift does not take place under normal circumstances, because external cues reset the clocks each day. Light is usually the most important cue, but many organisms can make use of rhythmic variations in temperature or other sensory inputs to readjust their internal timers. When a clock's error becomes large, complete resetting sometimes requires days.

This phenomenon is well known to long-distance air travellers as jet lag. Depression is considered another illness derived from 'the biological clock' going out of whack. It has been suggested that depression is associated with both quantitative and qualitative disturbances in sleep cycles. It has further been suggested that depressed people have disturbances in circadian rhythms including not only REM and sleep-awake cycles, but also the secretion of hormones such as cortisol, thyroid-stimulation hormone, and melatonin.

Healy and Williams (1988) have suggested, "The disturbance in circadian cycles causes the alterations in neurotransmitter balance as a secondary consequence, and provides a framework for interactions between biological and psychological factors responsible for the onset of clinical depression". An example of this is evident with overly studious students, who burn the candle at both ends (classes all day, work all weekend and study all night {caffeine induced}), these students often 'burn out', become exhausted, sick, clinically depressed or all of the above. There are numerous cycles being carried out throughout ones lifetime, some on a daily basis (circadian), some hourly (testosterone in males), and in the case of ovulation, 28 days is the norm, just to name a few. Understanding the triggers of the circadian cycle helps to explain why it is often hard to go back to bed once the light has caught your eye in the morning, or why it is often near impossible to stay up late enough to watch the end of your favourite sport on late night T.V. Fighting or tampering with natures clock is not conducive to homeostasis.

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