Testosterone and REM Sleep - Coursework Example

Testosterone and REM Sleep 13 April Testosterone and REM Sleep I. Introduction REM sleep and sex hormones are thought to have been linked previously in a world where many people have to sacrifice sleep due to jobs, children, and relationships. It is important to understand how sleep and sex hormones are correlated. The objectives of this study is to show correlation between REM sleep and testosterone in adult male sexual behavior; the study was done determine the effect of testosterone on male sexual behavior in rats deprived of REM sleep and also in relation to that, disruption of the nocturnal testosterone rhythm by sleep fragmentation in normal men. Through the observation made on the sexual behavior in REM deprived subjects, we can draw correlations between the two by establishing the negative effects deprivation has on testosterone and male sexual behavior. II. Facilitation of the effect of testosterone on male sexual behavior in rats deprived of REM sleep a. What was done Investigated the possibility of rapid eye movement in REM sleep deprivation (REMd), altering the effect of testosterone on masculine sexual behavior. Adult gonadectomized male rats with no sexual experience were randomly assigned to three groups, including REMd (using the water tank technique) for 7 days, large platform control for 7 days, and undisturbed sleep control. All the specimens were treated with testosterone propionate daily for 14 days. Masculine sexual behavior was assessed 3 days before the administration of steroid and daily during treatment. All of the REMd specimens presented mounts, intromissions, and ejaculations sooner than the control group. In almost all sequences, a facilitation of sexual activity was observed in the REMd group. Frequencies and length for mounts, intromissions, ejaculation, and duration of post ejaculatory refractory period were recorded (Velazquez-Moctezuma, Monroy, & Cruz, 1989). b. Methods The Methods that was used to carry out this experiment involved the use of adult male Wistar rats, which had no previous sexual experiments. The Wistar Rats were housed in groups of five per cage, food and water was placed in those cages, and addition of an inverted light cycle was provided. Before being used for the experiment, those Wistar Rats had been surgically altered with the males’ removal of their testis and the female extraction of their ovaries, a scientific term referred to as gonadectomy, at least 30 days before onset (Velazquez-Moctezuma Monroy, & Cruz, 1989). The Rats were randomly assigned to three different groups: In the first, Group A, the specimens were subjected to a series of undisturbed sleep-wake, the second group; in Group B, the Rats were allowed to attain slow wave sleep and then had to be awaken during REM sleep. In Group C, the rats were subjected to stress conditions. Velazquez further states that all the Rats in Group C were awakened using the technique used in Group B, but eventually allowed to complete periods of REM sleep (Velazquez-Moctezuma, Monroy, & Cruz, 1989). The experimental specimens were submitted to PSD using the modified multiple platform method, which involved placing the rats in acrylic water tank that contained 14 circular platforms, 6.5 cm in diameter with water up to 1 cm of their upper surface. This enabled the rats to move around inside the tank by jumping from one platform to another (Velazquez-Moctezuma, Monroy, & Cruz, 1989). When they reached the phase of sleep, muscle atonia set in, and they fell into the water and woke up. Throughout the study, the temperature of the experimental room was maintained at a controlled temperature (2361 uC) and light–dark cycle (lights on at 07:00 a.m. and off at 07:00 p.m.). Food and water were provided by placing chow pellets and water provided on bottles on a grid located on top of the tank. The water in the tank was changed daily throughout the SD period (Velazquez-Moctezuma, Monroy, & Cruz, 1989). c. Results The Results from this experiment showed that the number of days of treatment necessary to achieve response in half of the rats in the REM deprived group was one-half that of the same response in other groups. All rats had mounts and intromissions by day 8, with ejaculations by day 11. The stress condition control and the control group never reached that level of response, with 75% of the control rats ejaculating by day 14 (Velazquez-Moctezuma, Monroy, & Cruz, 1989). These genital reflexes were influenced by injection of testosterone propionate daily in Wistar rats; however, this scenario did not promote significant enhancement in PE and EJ in hypertensive rats, and the percentage of SHR displaying genital reflexes still figured significantly lower than that of the Wistar strain (Velazquez-Moctezuma, Monroy, & Cruz, 1989). As for hormone concentrations, both sleep-deprived Wistar and SHR showed lower testosterone concentrations than their respective controls. Sleep deprivation promoted an increase in concentrations of progesterone in Wistar rats, whereas no significant alterations were found after PSD in the SHR strain, which did not present enhancement in erectile responses. In order to explore the role of progesterone in the occurrence of genital reflexes, SHR were treated daily during the sleep deprivation period with progesterone. After the administration of this hormone, there was an observation of a significant increase in erectile events compared with the other group (Velazquez-Moctezuma, Monroy, & Cruz, 1989). III. Disruption of the Nocturnal Testosterone Rhythm by Sleep Fragmentation in Normal Men a. What was done Sleep can be described as a restoration process, which influences the nervous, neuro-endocrine and immune systems of the human body. Its considered important for health maintenance, and abnormal sleep behavioral patterns can lead to diseases such as cardiovascular diseases, mood disorders, chronic body pains, and other ailments, which can shorten life span of a person. A study was done whereby, ten healthy men ages 22-26 were subjected to a fragmented sleep schedule (7 minutes of sleep, 13 minutes awake) for a period of 24 hours. Their blood was tested for serum testosterone levels every 20 minutes in between the sleep cycles. They were fed liquid food every 3 hours, and their sleeping was monitored via electrodes. The results of their sleep recordings and their serum testosterone levels were compared to a group of six males who were subjected to a period of uninterrupted sleep (Luboshitzky, 2001). The human release of the testosterone from the testis occurs periodically and happens with body response to pulsatile gonadotropin stimulus. It peaks at around 0800h and lowers around 2000h; however, the cause of this rhythmic rise and fall of the release of testosterone at night has not been discovered yet. According to Luboshitzky (2001), among healthy aging men, there were positive correlations between sleep efficiency, REM latency, number of REM episodes, and the level of plasma testosterone. The attenuated testosterone levels have been associated with lack of or less sleep efficiency and prevalent decrease in REM episodes (Luboshitzky, 2001). In the study, it was further noted that the nocturnal testosterone rise in normal young adult men during continuous sleep started after they fell asleep and reached a plateau approximately 90 min later, at the approximate time of the first REM episode. The fall in the testosterone levels during the initial sleep period was significantly associated with REM latency and not with other sleeps stages. LH levels did not show much difference between the waking interval, REM, and non-REM intervals (Luboshitzky, 2001). This information shows that either the rise in testosterone may be basically related to first REM episode, or alternatively, both the rise in testosterone and the first REM latency reflect a common underlying circadian rhythm (Luboshitzky, 2001). In the study carried out, ten healthy men aged 22–26 years volunteered to participate in the study. They were all in good health condition, nonsmoking, within 10% of ideal body weight and received no medications. The Helsinki Committee of the Medical Center, Israel, approved the study, and all participants gave their informed consent before the onset of the study. The group was subjected to the fragmented sleep patterns; electrodes were attached, which measured REM latency in each 7-minute sleep stage. The group subjected to continuous sleep was measured using conventional methods. Serum testosterone levels were measured using a series of blood tests, in which the blood was drawn and then cooled until assayed (Luboshitzky, 2001). The study protocol involved the Subjects being admitted to the Sleep Research Center between 2200 and 2300h who were allowed to sleep between 0100 and 0600h for the habituation process, with electrodes attached for the purpose of sleep recordings. The subjects were awaken at 0600h, an IV catheter was inserted into their antecubital vein that kept patent by a slow infusion of 0.9% NaCl. At 0700h, subjects began an ultra short sleep paradigm, a schedule of 7-minutes sleep and 13-minutes awake for 24 hours. After every 20 minutes, they were placed in a dark room on their beds and instructed to attempt to fall asleep and electrophysiological recordings carried out during the 7-minute sleep attempts to determine the sleep stages (Luboshitzky, 2001). The subjects were asked to leave the rooms after the 7 minutes had elapsed regardless of whether they had fallen asleep or not. The light intensity in the rooms during the 13-minutes intervening wake period was set at a 50 lx and this process was repeated a total of 72 times, until 0700h the following day (Luboshitzky, 2001). Blood samples of about 3ml were collected from each subject after every 20 minutes in between sleeps attempts from the start 1900h to the stoppage 0700h. A complete balanced nutrition of approximately 355 cal/ Ml in line with the guidelines of Abbott Laboratories, Columbus Ohio -recommendations were provided to the subjects after every 3 hours interval (Luboshitzky, 2001). The results of this process and the recordings made of the levels of testosterone in the serum was compared to another study made of a group of six healthy men of similar characteristics who were tested after a continuous sleep between 2200h to 0700h. Throughout this study, the actual body temperature was recorded at an interval of once per minute using a scientific instrument known as the Minilogger 2000 (Mini-Mitter) with the help of the YSI, Inc. 400 disposable rectal probe (Luboshitzky, 2001). The sleep stages were analyzed using Electrodes, which were attached specifically to produce electrophysiological recordings: two electroencephalograms, two electro oculograms, and one electro myogram of the mentalis. These sleep stages were recorded in 30 sec epochs in line with the conventional criteria. Each of the 7-minutes trials was scored for sleep stages 1, 2, 3/4, and REM according to previously described criteria. Luboshitzky further reports that the sleep propensity function obtained is characterized by three features: an evening nadir in sleepiness, the sleep gate, and the nocturnal crest in sleepiness. The sleep gate, which represents an abrupt increase in sleep propensity from a low level during the forbidden zone to the nocturnal crest, was determined. It was during these trials that the subjects obtained at least 3.5 minutes of sleep of any stage followed by at least 5 of 6 trials meeting the same criterion (Luboshitzky, 2001). b. Methods Conventional methods were used to carry out the analysis of the sleep data about the continuous sleep group to determine sleep latency, sleep stages, and the REM latency of the subjects. REM latency in this situation is basically the time from sleep onset to the first appearance of REM sleep. Testosterone measurements were carried out by the centrifugation of blood, which was immediately separated and kept in temperate conditions of 220 C until was assayed; its levels were determined by the use of RIA for the coefficient variations and their concentrations, with the assay sensitivity discovered to be 0.15 nmol/L. Luboshitzky (2001) states that the serum for Melatonium level was determined after every 20 minutes intervals from 1900-0000h by the use of recommended standards of RIA. The concentrations, coefficient variations were determined and the assay sensitivity was found to be 2.0 pmol/L (Luboshitzky, 2001). c. Results The results found from the Disruption of the Nocturnal Testosterone Rhythm by Sleep Fragmentation in Normal Men experiment were as expected - the testosterone cycle in a healthy male was disrupted by fragmented sleep. While all six of the males who slept continuously had uninterrupted testosterone cycles, only four of the ten males who were part of the fragmented sleep group experienced their testosterone cycle, which was delayed by about five hours. To further investigate possibilities of the presence of a circadian rhythm in testosterone secretion, the levels of testosterone were synchronized according to the sleep gate in the 7/13 paradigm group. During continuous sleep, nocturnal rise in testosterone was observed when hormone levels were synchronized with either sleep or melatonin at onset time (Luboshitzky, 2001). There was a rise in the nocturnal testosterone due to fragmented sleep in subjects that had REM. This occurred when the hormone levels were synchronized with either melatonin onset time or with the sleep gate (Luboshitzky, 2001). In the young men who were used as the experimental subjects, the diurnal testosterone rhythm revealed higher levels at night and minimal in the late evening. The young men had significant diurnal rhythms in serum testosterone, although their Mean LH levels did not vary over the 24 hours. According to Luboshitzky (2001), several factors may be expected to influence the diurnal rhythm of testosterone; amongst these are LH, diurnal changes in Leydig cells response to LH, and intrinsic levels of gonadal. In healthy adult men, it was noted that the testosterone rhythm positively correlated with serum inhibin rhythm, with higher values in the early morning hours and lower values in the evening (Luboshitzky, 2001). The action of synchronization of the testosterone levels to melatonin onset did not reveal any change in testosterone levels in the fragmented sleep condition. In contrast, the nocturnal rise in melatonin does not rely on the factor of sleep and was shown to persist in the 7/13 paradigm of this experiment. IV. Discussion The results achieved from facilitation of the effect of testosterone on male sexual behavior in rats deprived of REM sleep experiment suggest that REM sleep facilitates the effects of testosterone on male sexual behavior. The effect is on the triggering mechanism versus the actual intensity of the activity (Velazquez-Moctezuma, Monroy, & Cruz, 1989). REM deprived rats needed half of what was needed by the other two groups to attain half of the responsiveness. Furthermore, it was confirmed that REMd increases the effects of testosterone on sexual behavior. During the present experiment, we found that the isolated factors (REM or testosterone administration) elicited erection and ejaculation, although not as evident as simultaneous association of REMd and testosterone injection (Velazquez-Moctezuma, Monroy, & Cruz, 1989). This effect of the REMd on testosterone administration could be attributed to the property of REMd in inducing several behavioral alterations. Luboshitzky further suggests that the brain systems form an integral part of the neural substrate of male sexual motivation and behavior. Drugs that stimulate brain receptors, also known as the DA neurons, can enhance sexual desire and arousal in animal males, and stimulate sexual behavior in male rats. This effect occurs due to the activation of DA mechanisms as a result of a reuptake block of monoamines neurotransmitters (Velazquez-Moctezuma, Monroy, & Cruz, 1989). One possibility to explain our finding could be that REMd causing the super sensitivity of brain neurons exacerbate the testosterone actions on brain pathways, inducing penile erection and ejaculation. Nevertheless, the experiment that was done on rats should at least be done on actual human beings to determine the same (Velazquez-Moctezuma, Monroy, & Cruz, 1989). These findings in III suggest a correlation between continuous sleep and the adult male testosterone cycle (Luboshitzky, 2001). Luboshitzky has further demonstrated that the major factors implicated in the testosterone changes were due to the increase in the saturation of the binding proteins (Luboshitzky, 2001). It cannot be excluded that changes in posture also contributed to our results. He further notes that on lying down of the subject, there is a significant decrease in protein concentration that is considered to be due to a shift of fluid into the vascular compartment under decreased hydrostatic pressure, this might lead to the dilution of non diffusible compounds found in the serum (Luboshitzky, 2001). In the experiment during the fragmented sleep, subjects were recumbent for the 7-minutes sleep attempts and then they left the bedroom for 13 minutes, at which time they were allowed to stretch and move around. Luboshitzky adds that, during the aspect of continuous sleep, subjects were active from 2200–0700h. Therefore, it is possible that changes in the postures of the subjects will have contributed to the loss of the nighttime rise in testosterone levels; hence, it is possible that the testosterone rhythm is dependent on a specific phase relationship between sleep and the underlying circadian. Further studies should elaborate this possibility (Luboshitzky, 2001). V. Conclusion In conclusion, the results from the experiment done on the young men showed that REM sleep has an effect on the triggering mechanism for testosterone in males. Several factors such as insomnia or sleeping problems have broader effects on men. Perhaps the effects of sleep deprivation are as a result hormonal changes to some extent. The experiment on rats gives us an explanation, whereby, through observation, we deduce that sleep may have a role on sex drive and perhaps performance. In future, my recommendation is that it would be important to translate the study from rats into a human study to establish if similar results would be achieved. References Luboshitzky, R. (2001). "Disruption of the Nocturnal Testosterone Rhythm by Sleep Fragmentation in Normal Men.” Journal of Clinical Endocrinology & metabolism, 86(3), 1134-9. Velazquez-Moctezuma, J. Monroy, E., & Cruz, M. (1989). Facilitation of the effect of testosterone on male sexual behavior in rats deprived of REM sleep. Behavioral and Neural Biology, 51(1), 46-53. Read More