Melatonin Capsules Research Articles

Pineal gland (melatonin) affects the parturition time, but not luteal function and fetal growth, in pregnant rats.

The purpose of the present study was to investigate the role of pineal gland (melatonin) on parturition time, luteal function, and fetal growth in pregnant rats. Cycling rats were subjected to pinealectomy or sham operation under ether anesthesia; and pinealectomized rats immediately underwent implantation of a melatonin capsule (PINX + Mel group) or a vehicle-containing capsule (PINX group), and sham operated rats also underwent implantation of a vehicle-containing capsule (control group). All rats were maintained under the same photoperiod conditions (14 L:10 D) and were induced pregnancy. Blood samples were obtained on days 7, 12, 15, 17, 19, and 21 of pregnancy to measure serum progesterone concentrations, and parturition times were recorded on days 22 and 23. In the next experiment, pregnant PINX rats received subcutaneous injection of melatonin (10 microg/body) at 08:00 h (PINX + 8 h group) or at 20:00 h (PINX + 20 h group) from day 15 to the end of pregnancy, and parturition times were recorded. Parturition times of rats in the PINX group, the PINX + Mel group or the PINX + 8 h group, but not the PINX + 20 h group, were significantly different compared with those in the control group. Pinealectomy or melatonin implantation did not affect serum progesterone concentrations during pregnancy or the number and weight of fetuses or corpora lutea. The present results indicate that pineal gland (melatonin rhythm) synchronizing with photoperiodic rhythm is likely to be an important determinant of parturition time, but it does not affect progesterone production or fetal growth in pregnant rats.

Independence of circadian entrainment state and responses to melatonin in male Siberian hamsters

BackgroundSeasonal fluctuations in physiology and behavior depend on the duration of nocturnal melatonin secretion programmed by the circadian system. A melatonin signal of a given duration, however, can elicit different responses depending on whether an animal was previously exposed to longer or shorter photoperiod signals (i.e., its photoperiodic history). This report examined in male Siberian hamsters which of two aspects of photoperiod history – prior melatonin exposure or entrainment state of the circadian system – is critical for generating contingent responses to a common photoperiodic signal.ResultsIn Experiment #1, daily melatonin infusions of 5 or 10 h duration stimulated or inhibited gonadal growth, respectively, but had no effect on entrainment of the locomotor activity rhythm to long or short daylengths, thereby demonstrating that melatonin history and entrainment status could be experimentally dissociated. These manipulations were repeated in Experiment #2, and animals were subsequently exposed to a 12 week regimen of naturalistic melatonin signals shown in previous experiments to reveal photoperiodic history effects. Gonadal responses differed as a function of prior melatonin exposure but were unaffected by the circadian entrainment state. Experiment #3 demonstrated that a new photoperiodic history could be imparted during four weeks of exposure to long photoperiods. This effect, moreover, was blocked in animals treated concurrently with constant release melatonin capsules that obscured the endogenous melatonin signal: Following removal of the implants, the gonadal response depended not on the immediately antecedent circadian entrainment state, but on the more remote photoperiodic conditions prior to the melatonin implant.ConclusionsThe interpretation of photoperiodic signals as a function of prior conditions depends specifically on the history of melatonin exposure. The photoperiodic regulation of circadian entrainment state contributes minimally to the interpretation of melatonin signals.

Researchers Identify Best Times For Effective Light Therapy

Researchers Identify Best Times For Effective Light Therapy

Polysomnographic study of the effect of melatonin on sleep in elderly patients with chronic primary insomnia

The effect of 3-mg melatonin capsules p.o. on sleep in ten elderly patients suffering from chronic primary insomnia was assessed by polysomnographic recordings. In general, melatonin significantly reduced wake time after sleep onset and increased total sleep time and sleep efficiency during the 2-week treatment period. In five of the ten patients treated with melatonin, the increase in total sleep time was clinically significant. Side effects were absent during the period of drug administration. A slight increase of power density in the delta and the theta regions was found during the early phase (i.e. nights 4–5) of melatonin administration, whereas the opposite changes were observed at a late phase of treatment (i.e. nights 15–16). No strict correlation was found between prior 6-sulphatoxymelatonin levels in urine and subsequent sleep improvement after receiving melatonin. Our results further support the proposal that melatonin is beneficial for sleep disturbances in elderly insomniacs.

Can melatonin improve adaptation to night shift?

This study was undertaken to determine whether melatonin ( N-acetyl-5-methoxytryptamine) is effective in helping emergency medical services (EMS) personnel who work rotating night shifts reset their biological clocks and minimize circadian rhythm disruption. A double-blinded, randomized, crossover study was performed using 22 volunteers. Participants were working a span of consecutive night (2300 to 0700 hours) shifts and received either a melatonin capsule (6 mg) or placebo to be taken before each of the consecutive day sleeps. Each participant completed a total of 4 spans of consecutive night shifts (2 melatonin, 2 placebo). Collected data included daily sleep diaries, quantification of alcohol/caffeine consumed, and drug side effects. Assessment of sleep quality, posttreatment mood, and workload ratings were measured daily by 10-cm visual analog scale (VAS). Analysis of sleep diaries found no significant difference ( P > .05) between the two treatments with respect to mean sleep latency, duration, and efficiency, and subjectively rated sleep quality. Similarly, no significant benefits were noted between the median VAS scores for daily posttreatment mood or workload ratings. Adverse effects were rare; one patient taking melatonin reported a prolonged sedative effect. Despite recent interest in melatonin for treatment of circadian-based sleep disorders, no clinical benefits were noted in EMS personnel working rotating night shifts.

The relationship between plasma testosterone concentrations and the seasonal variation in voluntary feed intake in fallow bucks (Dama dama)

In two experiments conducted at Badgery's Creek, NSW (Latitude 34°S) the roles of testosterone and the thyroid hormones triiodothyronine (T3) and thyroxine (T4) as possible initiators of the change in voluntary feed intake (VFI) associated with the seasonal reproductive behaviour (rut) in male fallow deer were investigated.In Expt 1, the association between changes in these hormones with the onset of the rut was assessed in deer in which the timing of this event was manipulated by changing the photoperiod, or by melatonin administration. Groups were maintained under either natural photoperiod (n=6; control), a constant long daylength (16 h light[ratio ]8 h dark; n=9; LD group) or a constant long daylength and implanted with melatonin capsules (n=5; LD+M group) for 7 months from December until the following July. Blood samples were obtained weekly and VFI recorded.Feed intake decreased by 94% from the last week of March for 3 weeks in the control group. Changes of a similar magnitude were measured in the LD and LD+M groups but these changes were advanced by 1 and 9 weeks respectively in these groups. In all groups, circulating testosterone concentrations increased markedly at a time corresponding with the decrease in VFI. The concentrations returned to basal levels with the resumption in VFI. A distinct decrease in plasma concentrations of T3 and T4 in all three groups was associated with the decrease in VFI, however, the relationship with T3 was less apparent.In Expt 2, the role of testosterone in the regulation of the decline in VFI was investigated. Fallow bucks were treated with testosterone enanthate every 4 or 5 days for 28 days up to 6 weeks prior to the expected onset of the rut. Plasma testosterone concentrations, which were increased 13-fold, resulted in a decline in VFI which was comparable to that observed in the subsequent rut. Plasma free fatty acid concentrations were correlated negatively with the decline in VFI.Thus, the seasonal increase in circulating testosterone concentrations plays an important role in initiating the fall in VFI associated with the rut. As the rut was still apparent in animals maintained under an extended photoperiod, it is possible that factors other than decreasing daylength act as the cue for the timing of the rut.

New dosage form for pulsatile delivery of melatonin: Development and testing in animal and human subjects

In the use of melatonin as a arcadian synchronizer in humans to treat a variety of rhythm disorders, it is desirable to develop controlled-release dosage forms that deliver melatonin in accordance with its endogenous secretory pattern, as well as preparations that release melatonin in a pulsatile manner. This paper describes the study of a new particulate dosage form for pulsatile delivery of melatonin (capsules B and C containing 10 mg each) in comparison with a fast-release form (capsule A containing 5 mg). The in vitro dissolution pattern of the dosage forms was characterized and completed by in vivo studies in dogs and male volunteers. Following oral administration of the melatonin preparations, the concentrations of both melatonin in serum (dogs and humans) and its main metabolite 6-sulfatoxymelatonin (aMEL6s) in urine (humans) were analyzed by means of specific radioimmunoassays. The following mean peak concentrations of melatonin in human serum were reached at 0.5–0.75 h (Cmax1pmol/ml): 20.7(A), 16.4 (B) and 9.1 (C). Capsules B and C released a second melatonin pulse after about 3.5 h, with Cmax2 of 13.0 and 17.5 pmol/ml, respectively. Dose proportionality for the melatonin preparations studied was calculated by determining the area under the curve (AUC0-10h) (pmol/ml, h): 18.4 (A), 36.1 (B) and 42.4 (C). The terminal serum half-lives of melatonin in male subjects ranged between 0.64 and 0.84 h. The time course of the renally excreted aMEL6s correlated with that of the respective melatonin serum concentrations.

Pinealectomy of melatonin implantation does not affect prolactin surge or luteal function in pseudopregnant rats.

The effects of melatonin on twice daily surges in PRL and luteal function were studied in pseudopregnant (PSP) rats. Cyclic rats received pinealectomy or sham operation under pentobarbital anesthesia on diestrus 1. Pinealectomized rats immediately received a melatonin capsule (the PINX+Mel group) or a blank capsule (the PINX group), and sham group of rats received a blank capsule (the control group). After operation, all rats were maintained under the same photoperiod conditions (14L: 10D), and estrous cyclicity was examined. At the 8th estrous cycle after operation, PSP was induced by mechanical stimulation of the uterine cervix. The last day on which the rat exhibited the estrous smear was designated as day 1 of PSP. Blood samples were obtained by jugular venipuncture under light ether anesthesia between 1200 and 1300 h on days 1, 3, 5, 7, 9 and 11, and between 0000 and 0100 h on day 13 of PSP. All rats were decapitated between 1200 and 1300 h on day 13 of PSP, and trunk blood was collected. A silicon catheter was inserted into the right jugular vein under ether anesthesia on day 4 of PSP. Blood samplings were performed every 2 h between 1000 h on day 5 and 1000 h on day 6 of PSP. Serum concentrations of melatonin, PRL and progesterone were measured by radioimmunoassay. Pinealectomy or melatonin installation did not disturb the estrous cyclicity or the induction of PSP. There were no differences among the three groups of rats during PSP in the pattern or serum PRL concentrations, and there were no significant differences among these three groups in the serum progesterone concentration or weight of the corpus luteum. The present results indicated that the continuously high or low melatonin in the physiological range did not affect the rhythm or strength of PRL surges or luteal function in PSP rats.

61. Can Melatonin Improve Adaptation To Night Shift? A Pilot Study Using an Urban EMS System

Purpose: To determine whether melatonin (N-acetyl-5-methoxytryptamine) is effective in helping prehospital personnel working consecutive night shifts reset their biological clock and minimize circadian rhythm disruption.Methods: A double-blinded, randomized, cross-over study was performed using 12 paramedic volunteers. Paramedics were working a span of consecutive night (2300-0700) shifts and received either a melatonin capsule (6 mg) or placebo to be taken prior to each of the consecutive day sleeps. Each participants completed a total of four spans of consecutive night shifts (2-melatonin, 2-placebo). Collected data included daily sleep diaries, quantification of alcohol/caffeine consumed, and possible drug side-effects. Assessment of job performance, mood and alertness were measured every day using 10-cm visual analog scales (VAS).Results: Analysis of sleep diaries demonstrated no significant difference (p >0.05) between the two treatments in respect to mean sleep latency (melatonin = 15.4 min. vs. placebo = 14.6 min), mean sleep duration (melatonin = 6.7 hrs. vs. placebo = 6.9 hrs), or subjectively rated sleep quality (melatonin = 5.8 VAS vs placebo = 5.6 VAS). Similarly, no significant benefits were noted between the mean VAS scores for daily job performance, mood and alertness. Adverse effects were rare, one patient taking melatonin reported a prolonged sedative effect.Conclusion: Despite widespread belief in the benefits of melatonin as a hypnotic agent, no clinical benefits were noted in terms of daytime sleep or job performance in paramedics working consecutive night shifts.

Response of collared lemmings to melatonin: I. Implants and photoperiod.

We examined the effect of constant-release melatonin capsules on the physiology and morphology of female collared lemmings exposed to either chronic long (22L:2D) or short (8L:16D) photoperiod, or to a change in photoperiod. When animals were maintained on unchanging long or short photoperiod, subcutaneous melatonin implants were without effect. However, when animals were reared on either 22L:2D or 8L:16D and transferred to the alternate photoperiod at weaning, melatonin (implanted at weaning) prevented most photoperiod-related responses. At sacrifice (after 8 weeks of treatment), melatonin-implanted animals exposed to a change in photoperiod did not differ from animals remaining in the original photoperiod with respect to pelage color, bifid claw size, uterine mass, or serum prolactin (PRL). In contrast, regardless of treatment, animals exposed to a photoperiod transfer developed a body mass that partially or fully reflected that characteristic of the secondary photoperiod; i.e., both control- and melatonin-implanted animals transferred from long to short photoperiod developed a large body mass. These results indicate that masking the endogenous melatonin rhythm via constant-release melatonin implants renders collared lemmings unable to respond to a change in photoperiod with respect to most physiological parameters. However, the striking seasonal change in body mass experienced by collared lemmings appears to be at least partially independent of a melatonin signal.

Melatonin implant decreases the density of 2[125I]iodomelatonin binding sites in the chicken spleen.

Changes in 2[125I]iodomelatonin binding to the chicken spleen following disruption of the normal melatonin rhythm by a slow-release melatonin implant were investigated. Melatonin capsules were implanted in 6-week-old male and female chickens reared under 12 h light/12 h darkness. The mid-light and mid-dark serum melatonin was measured throughout the period of implantation. Spleen weight and characteristics of splenic 2[125I]iodomelatonin binding sites were studied during the mid-light at 4 or 8 weeks after implantation. Melatonin implantation disrupted the normal diurnal rhythm of serum melatonin and elevated the mid-light level to the control mid-dark value until 5 weeks after implantation. The melatonin implant caused a significant decrease in the density of 2[125I]iodomelatonin binding sites at 4 weeks after implantation while there were no significant changes in the binding affinity. The reduction in 2[125I]iodomelatonin binding may be a result of down-regulation of the melatonin receptors by elevated serum melatonin. Alternatively, it may be due to an indirect suppression of 2[125I]iodomelatonin binding sites by the elevated sex hormones since melatonin implants increased the levels of testosterone in the male and estradiol in the female. Implantation of melatonin capsules significantly increased the body and spleen weights in the male chicken. These weight changes may be partly explained by the anabolic and erythropoietic action of the increased circulating testosterone.

Effects of melatonin treatment on the gonadotropin‐releasing hormone neuronal system and on gonadotropin secretion in male mink, Mustela vison, in the presence or absence of testosterone feedback

The effects of subcutaneous melatonin capsules on the gonadotropin-releasing hormone (GnRH) immunoreactive (ir) system and the secretion of follicle stimulating hormone (FSH) and luteinizing hormone (LH) have been tested in intact, castrated, and castrated adult male mink supplemented with testosterone. Animals were transferred in July, i.e., during the period of sexual rest, under a daily light:dark cycle of 16-hr light and 8-hr darkness and studied over 13 weeks. GnRH (ir) perikarya, visualized by immunocytochemistry, were counted on serial coronal sections from the diagonal band of Broca to the infundibulum. Serum FSH and LH concentrations were measured by radioimmunoassay. In intact mink, melatonin induced a significant increase in the number of (ir) perikarya and in FSH and LH concentrations 3 and 8 weeks, respectively, after melatonin capsule implantation. In castrated mink, the number of perikarya and the concentrations of FSH, which had increased within 2 weeks after castration, did not change during melatonin treatment. In contrast, the concentration of LH, which were not altered by castration, increased 3-6 weeks after the onset of melatonin administration, suggesting a stimulation of GnRH release. In castrated testosterone-treated mink, the number of perikarya was increased as in castrated males, but the elevation of FSH in response to castration was prevented. Within 2 weeks after melatonin capsule implantation, the concentrations of FSH decreased while those of LH remained low, indicating an inhibition of GnRH release. These results show that testosterone modulates the effect of melatonin on the activity of the GnRH-gonadotropin system.

Endogenous circannual rhythms and photorefractoriness of testis activity, moult and prolactin concentrations in mink (Mustela vison).

Mink are seasonal photosensitive breeders; testis activity is triggered when days have less than 10 h light. Increasing and decreasing plasma concentrations of prolactin induce the spring and autumn moults. In a 5 year experiment, males were maintained under short days (8 h light:16 h dark) at 13 degrees C or long days (16 h light:8 h dark) at 21 degrees C, winter and summer conditions, respectively. Under winter and summer conditions, circannual cycles of prolactin secretion and moulting were observed at intervals of about 11 months. Recurrence of testis cycles was not evident. In a second experiment, males were maintained under an 8 h light:16 h dark cycle from the winter solstice or under 10 h light:14 h dark, 12 h light:12 h dark or 14 h light:10 h dark cycles from 10 February. Under 8 h light:16 h dark cycle, testis regression was slightly later than under natural conditions, indicating photorefractoriness. However, mink remained sensitive to light: the longer the photoperiod, the faster the testis regression. In a third experiment, males were transferred under 8 h light:16 h dark or 16 h light:8 h dark from 15 May (group 1), 12 June (group 2) or 4 July (group 3); males submitted to long days received melatonin capsules on the day of transfer. Increasing concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and testis volume were shown by half the males in group 2 and nearly all the males in group 3; the constant release of melatonin from implants was more efficient than short days; but in the three groups, prolactin concentrations decreased in the few days after short-day or melatonin treatment. Overall, the results demonstrate endogenous circannual rhythms of prolactin secretion, body weight and moulting. Although a refractory period to short days was observed, the annual cycle of testis activity totally relies on the annual changes in daylength.

Melatonin but not the ram-effect reactivates quiescent ovarian activity of mid-anestrous ewe.

The present study was conducted to examine how the social cue emanating from rams, the ram-effect, would influence the onset of melatonin-induced reproductive activity in anestrous ewes. Twenty non-lactating ewes were randomly allocated into 4 groups as follows based on a combination of the melatonin treatment (MEL) and the ram-effect (RAM): ewes of Groups A (MEL + RAM) and B (MEL) were subcutaneously implanted with melatonin capsules on April 18 (Day 0), which increased plasma melatonin levels by about 200 pg/ml for at least 5 months, while Groups C (RAM) and D (control) were untreated with melatonin. Rams were introduced to Groups A and C on Day 0, whereas Groups B and D were isolated from rams. Ovarian function of the ewe was assessed on June 9-21 (Days 52-64) by monitoring plasma progesterone (P) profiles. Luteal function (plasma P greater than 1 ng/ml for a week or longer) was evident in all the melatonin-treated ewes but only one in those untreated: 5/5 in Group A, 5/5 in Group B, 1/5 in Group C and 0/5 in Group D. By ultrasonography on Day 105 all the Group A ewes were diagnosed pregnant but none in the Group C despite that both the two groups had been run with rams. These results indicate that chronic melatonin treatment is capable of advancing the reproductive recrudescence in seasonally anestrous ewes, and that progonadal effects of rams are subtle, if any, during the mid-anestrous period.

Effect of photoperiod and melatonin on cold resistance, thermoregulation and shivering/nonshivering thermogenesis in Japanese quail.

The effect of photoperiod and melatonin treatment on cold resistance and thermogenesis of quails was studied. The birds were acclimated for 8 weeks to short day (8L:16D) or long day (16L:8D) conditions, and 8 of 16 quails in each group were implanted with melatonin capsules. One group of quails was maintained outside in an aviary during winter. Oxygen consumption (VO2), body temperature (Tb, recorded with temperature transmitters) and shivering (integrated pectoral EMG) were recorded continuously, and samples of heart rate and breathing rate were picked up when ambient temperature was decreased stepwise from 27 down to -75 degrees C. Heat production maximum (HPmax), cold limit, lower critical temperature, basal metabolic rate (BMR) and thermal conductance were determined. The results show that short day, cold and melatonin treatment improved cold resistance and thermal insulation of quails when compared with quails acclimated to long day conditions. An increase in HPmax was induced only by melatonin treatment. The results suggest that the acclimatization of quails is under control of the pineal gland. The linear increase of shivering intensity with VO2 at moderate cold load shows that shivering is the primary source for thermoregulatory heat production in the quail. At Ta's below -40 degrees C shivering remained constant although VO2, heart rate and breathing rate continued to increase with increasing cold load. This could indicate the existence of a nonshivering thermogenesis in birds. Unlike to mammals, this non-shivering thermogenesis in birds would serve as secondary source of heat supporting shivering thermogenesis in severe cold.

Role of the pineal gland in the photoperiodic control of reproductive and non-reproductive functions in mink (Mustela vison).

Mink are long-lived mammals that exhibit seasonal changes in body weight, gonadal activity, pelage and plasma prolactin levels. Mating in February-March is followed by an obligatory delay in implantation during which the corpora lutea stay quiescent. All these events are controlled by annual variations in daylength. The role of the pineal gland and its product, melatonin, in conveying photic information to the target organs has been studied. Pineal denervation by bilateral ablation of the cervical superior ganglia rendered the mink unresponsive to artificial manipulations of the daily photoperiod: prolactin and progesterone secretion and the spring moult were no longer stimulated by long days or inhibited by short days in pregnant females; in the same way the increase in body weight in late summer and the autumn moult were no longer advanced by artificial shortening of the photoperiod. Pinealectomy seemed to desynchronize body weight, prolactin and moulting cycles from those in intact mink. Melatonin injections reproduced the effects of short days on hormonal secretion during the delayed implantation period. Melatonin capsules given to males during the phase of testicular activity delayed the decrease in body weight, testicular regression and onset of the spring moult exactly as did short days. In contrast, melatonin administered during the phase of testicular inactivity triggered an increase in body weight, the onset of the spring moult and testicular recrudescence in this short-day breeder. These results support the hypothesis that in mink all photoperiodic signals are conveyed by the pineal gland. But although the pineal seems essential for the seasonal timing of the cycles, it does not modify the events themselves once they are initiated.

The seasonal cycle of body weight in the Djungarian hamster: photoperiodic control and the influence of starvation and melatonin

Photoperiod is the primary environmental cue for seasonality in the Djungarian hamster (Phodopus sungorus). This species reduces its body weight by 30% during winter to reduce its energy requirements. The aim of this study was (1) to examine the influence of food intake on the body weight cycle and (2) to evaluate the role of photoperiod and melatonin in determining this seasonal cycle.While body weight increased slightly (7%) from August through December in long photoperiod, it dropped significantly (32%) in the natural photoperiod group and food intake gradually decreased in this group by about 20%. After two periods of 40% food restriction, the hamsters in long photoperiod rapidly returned to their initial body weight. In contrast, hamsters under natural photoperiod only gained weight until they had reached the body weight of the controls at that particular time.In a second experiment, hamsters were kept under natural photoperiod throughout the year. At 6 different intervals two groups of hamsters were implanted with melatonin capsules and transferred to either short (LD 8:16) or long photoperiod (LD 16:8). The results show that the seasonal change in body weight is caused by a combined action of photoperiod and a change in the animals' sensitivity towards photoperiod and melatonin.

Effects of shortened daylength and melatonin treatment on plasma prolactin and melatonin levels in pinealectomised and sham-operated ewes

Comparisons have been made between the effects of shortened daylength and melatonin treatment on plasma prolactin and melatonin levels in pinealectomised (Px) and sham-operated (Sh) ewes. Twenty-two anoestrous Merino crossbred ewes, maintained under normal grazing conditions, were assigned to four groups for a period of 9 weeks. Group 1 remained untreated (control), Group 2 was herded into a dark shed at 1600 h each day until dark (approx 4 h), ewes in Group 3 were injected with 100 μg melatonin s.c. at 1600 h each day and ewes in Group 4 were implanted with a melatonin capsule releasing 125–200 μg/day. Another group (Group 5) of 4 Px and 4 Sh ewes from the same flock was maintained in an animal house and subjected to shortened daylength (10. 5 h L : 13. 5 h D, lights off 1600 h). Three weeks after the treatments began, ewes in Groups 1–4 were exposed to a fertile ram and ewes in Group 5 to a vasectomised ram and the day of mating noted. No differences were evident between Groups 1–4 in the ewes' response to the ram, time taken to conceive, duration of gestation or number of lambs born. In untreated Px ewes no plasma melatonin (< 20 pg/ml) was found in either day or night samples, whereas intact animals showed the characteristic night-time rise. The silastic implants produced stable daytime blood levels of 90–120 pg/ml, whereas a single injection of 100 μg melatonin caused a transitory (2–3 h) rise. Shortened daylength (Group 2) or a single daily injection of melatonin (Group 3) lowered prolactin levels but only in ewes with an intact pineal gland, whereas melatonin implants (Group 4) caused a reduction in plasma prolactin in both Px and Sh sheep. The results indicate that light-induced alterations in prolactin production in sheep involve both the pineal gland and melatonin. Continuous melatonin release from implants caused changes in plasma prolactin levels similar to those seen following exposure to short days.

Effects of pinealectomy and subsequent melatonin implants on activity rhythms in the house finch (Carpodacus mexicanus)

Activity patterns were analyzed in house finches which were pinealectomized and subsequently implanted with melatonin capsules. Most pinealectomized house finches showed loss of circadian perch-hopping rhythms in constant darkness (DD). Total amount of activity in DD was about 175% higher in pinealectomized than in intact finches. In a light-dark cycle (LD) with 8 h L and 16 h D, activity in pinealectomized birds was redistributed such that an increase in activity during phase lead counter-balanced a decrease during L. Mean duration of phase lead increased from 1/2 h in intact finches to about 3 1/2 h in pinealectomized birds. Melatonin capsules implanted in pinealectomized finches shortened phase lead in LD and lengthened phase trail, suggesting a role for melatonin levels in setting the phase of the activity rhythm apart from phasic changes in melatonin release. Melatonin did not restore circadian rhythmicity in pinealectomized finches and instead was associated with a decline in signs of residual, damped rhythmicity. Amount of 24-h activity was positively correlated with percentage of total activity occurring during daytime; both of these were inversely correlated with melatonin dosage. In pinealectomized finches, the amount of DD activity correlated positively with phase lead activity in LD, but not with amount of activity during L. The data are interpreted in terms of the hypothesis that phase lead represents a component of activity rhythms governed by a damped oscillator of non-pineal location but influenced by melatonin.

Melatonin prevents decrease in plasma PRL and LH levels in male hamsters exposed to a short photoperiod.

Treatment of male golden hamsters with melatonin injections can cause a decrease in plasma gonadotropin and Prl levels and induce testicular regression. However, administration of melatonin via subcutaneously implanted Silastic capsules can prevent short photoperiod from causing the testes to regress. In order to explain this effect of melatonin capsules, we examined plasma Prl, LH and FSH levels in pinealectomized and sham-operated hamsters in which empty or melatonin-filled Silastic capsules had been implanted. After implantation, the hamsters were transferred to a short photoperiod (5 h L:19 h D) for 9 weeks. Both pinealectomy and melatonin completely prevented the decline in plasma Prl and LH levels and in the weight of the testes and the seminal vesicles. Moreover, testicular weight and plasma Prl and LH levels were higher in pinealectomized animals given melatonin capsules than in pinealectomized animals given empty capsules. In order to obtain some indication whether melatonin may affect testicular function directly, we have examined the influenced of melatonin on the production of testosterone by hamster testes in response to hCG in vitro. Addition of 0.2, 10 or 500 ng of melatonin per ml of incubation medium had no effect on testosterone production in this system. It is concluded that melatonin capsules prevent regression of the male reproductive system in short photoperiod, most likely by preventing the decline in plasma Prl and LH levels and that these effects of melatonin are not mediated through or dependent on the pineal.