Effect of single neonatal melatonin treatment on in vitro thyroxin secretion and TSH or melatonin-modified cAMP level of one-month-old rats

At the age of one month, incubation with melatonin of the thyroid glands of rats having received a single melatonin treatment at the age of three days resulted in increased thyroxine production. TSH was unable to enhance the thyroxine production of animals treated with melatonin neonatally, while its considerable increase could be observed in the case of control animals. Simultaneous TSH and melatonin treatment applied in vitro at the age of one month resulted in an approximately twofold increase of thyroid T4 production in rats having received neonatal melatonin treatment. In vitro alteration of the cyclic AMP level of the thyroid glands of intact and neonatally melatonin treated rats ran practically parallel, except that in the melatonin treated animals the cAMP level was higher after TSH administration. At the same time the cAMP level decreased in the thyroid gland of animals treated with TSH + melatonin. There was no exact correlation between the alterations of cAMP and T4 levels in the given experimental system.     

Serum concentrations of melatonin during scotophase and photophase in 3, 4, 5 and 6 months old gilts and barrows

One-hundred-twenty prepubertal crossbred gilts (Hampshire x Duroc) x (Yorkshire x Landrace) were removed from the nursery at 68.7+/-0.4 days of age and 23.6+/-0.9 kg body weight and relocated to a conventional grower-finisher unit. In addition, 60 barrows of similar genetics were relocated from the nursery at 71.0+/-0.5 days of age and 27.4+/-0.5 kg body weight to the same building. Twelve mature anestrous ewes that weighed 77.0+/-2.4 kg were assigned randomly to one of four pens of equal dimensions among the pens containing pigs. Ewes were included in this study to serve as positive controls since their secretory profiles of melatonin are well characterized. All pigs were bled by jugular venipuncture at approximately 3, 4, 5 and 6 months of age. At each age in the pigs and the mature ewes, a single sample was obtained during photophase and scotophase. Illumination intensity during the period of incandescent lighting averaged 220 1x. Blood collection was initiated approximately 4 h after sunrise and 3.5-4 h after sunset. The proportion of animals that exhibited a nocturnal rise in melatonin (MEL) was similar (P > 0.05) between gilts and barrows, but was higher (P < 0.002) in ewes than in pigs at each age examined. A greater proportion (P = 0.007) of 3 month old barrows had a nocturnal rise of MEL than any other age of barrow. Similarly, there was a tendency (P = 0.06) for more 3 month old gilts to exhibit a nocturnal increase in serum MEL than 4, 5 or 6 month old gilts.     

Influence of exogenous thyroxine on plasma melatonin in juvenile Atlantic salmon (Salmo salar)

One of the most clearly defined endocrine changes during the parr-smolt transformation of anadromous salmonids is an increase in plasma levels of thyroid hormones. The role of pineal hormone melatonin in timing and synchronisation of smoltification is widely discussed. The effect of administration of exogenous thyroxine (T4) on plasma melatonin was investigated in juvenile Atlantic salmon (Salmo salar) at the early stages of parr-smolt transformation. Fish were kept in fresh water under simulated-natural photoperiod and exposed to exogenous T4. Fish were sampled at 12.00 and 24.00 h from treatment and control tanks, 2 and 14 days after treatment started. Plasma melatonin and L-thyroxine were measured using RIA and competitive enzyme immunoassay, respectively. After 2 days of T4 treatment, marked difference in plasma melatonin concentration measured at 12.00 and 24.00 h was still observed in both groups. However, 2-week exposure to T4 caused a reduction in night-time plasma melatonin level and thus, probably, inhibited melatonin related time-keeping system in juvenile salmon. Additional studies are needed to clarify the mechanism of the described phenomenon.     

Electric field exposure alters serum melatonin but not pineal melatonin synthesis in male rats

Sprague-Dawley male rats, maintained in a 14:10 h light:dark cycl were exposed for 30 days (starting at 56 days of age) to a 65 kV/m, 60 Hz electric field or to a sham field for 20 h/day beginning at dark onset. Pineal N-acetyltransferase (NAT), hydroxy-indole-o-methyl transferase (HIOMT), and melatonin as well as serum melatonin were assayed. Preliminary data on unexposed animals indicated that samples obtained 4 h into the dark period would reveal either a phase delay or depression in circadian melatonin synthesis and secretion. Exposure to electric fields for 30 days did not alter the expected nighttime increase in pineal NAT, HIOMT, or melatonin. Serum melatonin levels were also increased at night, but the electric field-exposed animals had lower levels than the sham-exposed animals. Concurrent exposure to red light and the electric field or exposure to the electric field at a different time of the day-night period did not reduce melatonin synthesis. These data do not support the hypothesis that chronic electric field exposure reduces pineal melatonin synthesis in young adult male rats. However, serum melatonin levels were reduced by electric field exposure, suggesting the possibility that degradation or tissue uptake of melatonin is stimulated by exposure to electric fields. © 1994 Wiley-Liss, Inc.     

Effect of melatonin implants on secretion of luteinizing hormone in intact and castrated rams

Rams were treated with melatonin implants in 2 experiments designed to examine the control of reproductive seasonality. In Exp. 1, rams (n = 12) were allocated to 3 treatment groups: 2 groups were treated with 2 melatonin implants per ram for 4 months from 11 November (N) and 9 December (D) and the remaining group was untreated (C). The seasonal increase in luteinizing hormone (LH) pulse frequency and testes size was advanced in Groups N and D. A second seasonal cycle in LH secretion and testes size occurred in Groups N and D after melatonin implants became exhausted. In Exp. 2, rams (n = 20) were allocated to 4 treatment groups: 10 rams were castrated on 6 October and 1 group of entire rams (EM) and one group of castrated rams (CM) were treated with 2 melatonin implants per ram each month from 3 November until 8 January. The other group of entire rams (EC) and castrated rams (CC) was untreated. An increase in LH pulse frequency occurred after castration. Melatonin treatment increased LH pulse frequency in entire rams and reduced LH pulse frequency in castrated rams. The results demonstrated that the advanced reproductive development as a result of treatment with melatonin implants was due to an effect of melatonin on the hypothalamic pulse generator to increase LH pulse frequency. The ability of melatonin to influence LH pulse frequency in entire and castrated rams indicated that an effect of melatonin on the hypothalamic pulse generator is independent of testicular steroids.     

Direct influence of melatonin on the thyroid and comparison with prolactin

Melatonin administered in vivo had previously been shown to inhibit thyroid cell proliferation and subsequent in vitro thyroxine (T(4)) secretion in anuran tadpoles. Melatonin in vitro also directly reduced the sensitivity of the thyroid to thyrotropin (TSH). The present work sought to determine whether melatonin directly affected baseline, unstimulated T(4) secretion, and to compare its effect with that of prolactin (PRL). Thyroids from larval Rana catesbeiana or adult Rana pipiens were incubated in control or melatonin (0.01 to 100 microg/ml) media. Melatonin directly inhibited T(4) secretion by thyroids from both tadpoles and frogs at all concentrations of melatonin used and at both prometamorphic and climax tadpole stages. PRL, used in vitro at 10 microg/ml, did not influence the response of the thyroid to TSH (0.2 microg/ml) in young tadpoles, or the baseline secretion of T(4) by thyroids at any stage of larval life except climax, when T(4) secretion was significantly decreased by the third day of culture. Thus although both melatonin and PRL have been shown to antagonize the action of T(4) in vitro, and to decrease metamorphic rate, melatonin is a much more effective thyroid gland inhibitor than PRL.     

The decrease in plasma melatonin at metamorphic climax in Rana catesbeiana (bullfrog) tadpoles is induced by thyroxine.

Melatonin decreases in the plasma of Rana catesbeiana (bullfrog) tadpoles at the climax of metamorphosis when the thyroxine (T(4)) level peaks. Since melatonin inhibited thyroid function in vitro, it would be of interest to determine if the decline in plasma melatonin permits greater thyroid hormone secretion, or if the increasing levels of T(4) cause the climactic decrease in plasma melatonin. The reciprocal effects of administering T(4) or melatonin just prior to metamorphic climax were examined in tadpoles kept at 22 degrees C on an 18L:6D cycle. If melatonin functions as a thyroid antagonist at later metamorphic stages, administration of melatonin should decrease plasma T(4), whereas if T(4) causes the decline in plasma melatonin, T(4) treatment of tadpoles prior to climax should induce the climactic melatonin decrease prematurely. Once daily injection of 40 microg melatonin for 5 days at 19.30 h had no effect on metamorphic progress, or on plasma T(4) or melatonin levels, except for a transient rise in melatonin just after the injection. Immersion in 2.2x10(-4) M melatonin for 6 days accelerated metamorphosis and decreased plasma melatonin, but had no effect on plasma T(4). Administration of T(4) by injection of 0.2 microg, or immersion in a 6.3x10(-8) M solution accelerated metamorphosis more than melatonin immersion, raised plasma T(4) to climax levels, and induced a decrease in plasma melatonin. We conclude that rapid clearance of exogenous melatonin from the circulation in these experiments did not allow it to affect plasma T(4), and that there is clear evidence that the rise in T(4) induces the climax decrease in plasma melatonin. The finding that immersion in a high level of melatonin can lower plasma melatonin and accelerate metamorphosis, whereas a single daily injection does not, provides an explanation for some of the contradictory reports in the literature concerning melatonin's effect on tadpole metamorphic progress.     

Pituitary response to LHRH, LH pulsatility and plasma melatonin and prolactin changes in ewe lambs treated with melatonin implants to delay puberty

Prepubertal ewe lambs were treated with empty or filled melatonin implants. The implants were placed s.c. at birth and pituitary responsiveness to various doses of LHRH, LH/FSH pulsatility and prolactin and melatonin secretion were examined at 10, 19, 28, 36 and 45 weeks of age. Control animals (N = 10) showed no consistent alteration in pituitary responsiveness to LHRH during development. Ewes treated with melatonin (N = 10) had puberty onset delayed by 4 weeks (P less than 0.03) but no effect of melatonin on LH or FSH response to LHRH injection was observed at any stage of development. In the control and melatonin-treated ewe lambs the responses to LHRH injection were lower during darkness than during the day at all stages of development. No consistent differences in LH or FSH pulsatility were observed between treatment groups or during development. Prolactin concentrations, however, failed to decrease at the time of puberty (autumn) in the melatonin-treated group. Melatonin-treated ewe lambs maintained normal rhythmic melatonin production which was superimposed on a higher basal concentration and showed the same increase in melatonin output with age as the control ewes. These results indicate that the delayed puberty caused by melatonin implants is not due to decreased pituitary responsiveness to LHRH or to dramatic changes in basal LH or FSH secretion.     

Circadian regulation of pineal melatonin and reproduction in the Djungarian hamster

Gonadal state, pineal melatonin rhythms, and locomotor activity rhythms were examined in juvenile male Djungarian hamsters exposed to non-24-hr light cycles ("T-cycles") or to full photoperiods. At the end of 1 month, hamsters exposed to a 1-hr pulse of light every 24.33 hr (T 24.33) exhibited small testes, whereas those receiving the same amount of light every 24.78 hr (T 24.78) displayed stimulated gonads, ten-fold larger in size. Accompanying the nonstimulatory effect of the T 24.33 cycle were nocturnal peaks in both pineal melatonin content and serum melatonin concentration which were longer by approximately 4 hr than those observed on the photostimulatory T 24.78 cycle. Exposure to an intermediate-length T-cycle (T 24.53) resulted in a mixed gonadal response and in pineal and serum melatonin peaks of intermediate duration. Wheel-running activity was entrained to the T-cycles such that light was present only near the beginning of the subjective night, its phase (relative to activity onset) differing only slightly among T-cycle groups. Hence the durational differences observed in the melatonin peaks were apparently not due to the acute suppressive or phase-advancing effects of morning light on melatonin biosynthesis, but were rather the result of differences in the endogenous control of pineal activity by the circadian pacemaker system. While no strong correlation was detected between gonadal state and the phase of locomotor activity onset relative to the light pulse, a significant correlation was observed between gonadal state and the duration of daily locomotor activity (alpha). These data were compared to similar measures obtained from hamsters exposed to long-versus short-day full photoperiods (LD 16:8 vs. LD 10:14). In summary, the results of this study indicate involvement of the circadian pacemaker system of Djungarian hamsters in the control of pineal melatonin synthesis and secretion, and in photoperiodic time measurement. Furthermore, these data strengthen the hypothesis that it is the duration of nocturnal pineal melatonin secretion that is the critical feature of this neuroendocrine gland's photoperiodic signal.     

The effects of melatonin and hypothyroidism on estradiol and gonadotropin levels in female Syrian hamsters

Since melatonin injections administered near the end of the daily photoperiod influence both gonadal and thyroid hormones in the female hamster, the present study was designed to compare the effects of melatonin and hypothyroidism on the reproductive system and to determine whether thyroid status influenced the action of melatonin on the regulation of the hormones of reproduction. The effects of daily melatonin injections were determined in control hamsters, in hamsters rendered hypothyroid with thiourea, and in hypothyroid hamsters receiving thyroxin (T4) hormone replacement. As previously reported, melatonin injections disrupted estrous cyclicity, disrupted the normal pattern of gonadotropin secretion, and resulted in atrophy of the uterus and vagina. These changes coincided with depressed serum and pituitary prolactin (PRL), and depressed levels of estradiol. The effects of melatonin on uterus, vagina, ovary, and on gonadotropin levels were not prevented by T4 replacement, with the exception of a melatonin-induced increase in serum follicle-stimulating hormone (FSH). This suggested that the cessation of estrous cyclicity was not primarily a result of thyroid deficiency. Hypothyroidism, however, like melatonin, resulted in a reduced number of developing and mature follicles and corpora lutea in the ovaries, and in reduced uterine weight. It also produced follicular atresia, reduced the circulating levels of estradiol, and resulted in reduced incidence of estrus smears. T4 replacement, for 2 weeks, prevented the decline in mature follicles and corpora lutea, reduced the extent of follicular atresia, increased circulating levels of estradiol, and increased uterine weight. PRL and luteinizing hormone (LH) data also provided evidence for antagonistic effects of melatonin and T4 in female hamsters. These data raise the question whether melatonin-induced changes in circulating levels of T4 play a role in the seasonal cycles of reproductive competence in the female hamster.     

Seasonal and daily variations in plasma melatonin in the high-arctic Svalbard ptarmigan (Lagopus mutus hyperboreus).

This study presents the daily rhythm of melatonin secretion throughout one year in a bird from the northern hemisphere, the Svalbard ptarmigan (Lagopus mutus hyperboreus), which lives naturally at 76-80 degrees N. Eight Svalbard ptarmigan were caged outdoors at 70 degrees N and blood sampled throughout one day each month for 13 months. At this latitude, daylight is continuous between May and August, but there is a short period of civil twilight around noon from late November to mid January. There was no daily rhythm in plasma melatonin in May-July. Plasma melatonin levels varied significantly throughout the day in all other months of the year, with the nighttime increase reflecting the duration of darkness. The highest mean plasma concentration occurred at midnight in March (110.1 +/- 16.5 pg/ml) and represented the annual peak in estimated daily production. Around the winter solstice, melatonin levels were significantly reduced at noon and elevated during the nearly 18 h of consecutive darkness, and the estimated mean daily production of melatonin was significantly reduced. Thus, at the times of the year characterized by light-dark cycles, melatonin may convey information concerning the length of the day and, therefore, progression of season. The nearly undetectable low melatonin secretion in summer and the reduced amplitude and production in midwinter indicate a flexible circadian system that may reflect an important adaptation to life in the Arctic.     

Less exposure to daily ambient light in winter increases sensitivity of melatonin to light suppression

This study was carried out to examine the seasonal difference in the magnitude of the suppression of melatonin secretion induced by exposure to light in the late evening. The study was carried out in Akita (39 degrees North, 140 degrees East), in the northern part of Japan, where the duration of sunshine in winter is the shortest. Ten healthy male university students (mean age: 21.9+/-1.2 yrs) volunteered to participate twice in the study in winter (from January to February) and summer (from June to July) 2004. According to Japanese meteorological data, the duration of sunshine in Akita in the winter (50.5 h/month) is approximately one-third of that in summer (159.7 h/month). Beginning one week prior to the start of the experiment, the level of daily ambient light to which each subject was exposed was recorded every minute using a small light sensor that was attached to the subject's wrist. In the first experiment, saliva samples were collected every hour over a period of 24 h in a dark experimental room (<15 lux) to determine peak salivary melatonin concentration. The second experiment was conducted after the first experiment to determine the percentage of melatonin suppression induced by exposure to light. The starting time of exposure to light was set 2 h before the time of peak salivary melatonin concentration detected in the first experiment. The subjects were exposed to light (1000 lux) for 2 h using white fluorescent lamps (4200 K). The percentage of suppression of melatonin by light was calculated on the basis of the melatonin concentration determined before the start of exposure to light. The percentage of suppression of melatonin 2 h after the start of exposure to light was significantly greater in winter (66.6+/-18.4%) than summer (37.2+/-33.2%), p<0.01). The integrated level of daily ambient light from rising time to bedtime in summer was approximately twice that in winter. The results suggest that the increase in suppression of melatonin by light in winter is caused by less exposure to daily ambient light.     

Feeding melatonin enhances the phase shifting response to triazolam in both young and old golden hamsters

Aging alters many aspects of circadian rhythmicity, including responsivity to phase-shifting stimuli and the amplitude of the rhythm of melatonin secretion. As melatonin is both an output from and an input to the circadian clock, we hypothesized that the decreased melatonin levels exhibited by old hamsters may adversely impact the circadian system as a whole. We enhanced the diurnal rhythm of melatonin by feeding melatonin to young and old hamsters. Animals of both age groups on the melatonin diet showed larger phase shifts than control-fed animals in response to an injection with the benzodiazepine triazolam at a circadian time known to induce phase advances in the activity rhythm of young animals. Thus melatonin treatment can increase the sensitivity of the circadian timing system of young animals to a nonphotic stimulus, and the ability to increase this sensitivity persists into old age, indicating exogenous melatonin might be useful in reversing at least some age-related changes in circadian clock function.     

Cardioprotective activity of melatonin and its novel synthesized derivatives on doxorubicin-induced cardiotoxicity

This study aimed at evaluation of melatonin and some of its novel synthesized derivatives 3, 4, 9 and 10b as cardioprotective agents against doxorubicin-induced acute cardiac toxicity in rats. Also, this work was extended to study the potential role of each synthesized derivative in comparison with the parent compound melatonin. Intraperitoneal injection of a single dose (15mg/kg B.W.) of doxorubicin resulted in significant increase in serum troponin I, leptin, triglycerides, cholesterol and LDL-cholesterol levels with concomitant decrease in serum T(3), T(4) and IL-1alpha levels. In contrast, intraperitoneal injection of melatonin or its synthesized derivatives especially compounds 3 and 10b in a dose of 5mg/kg B.W./day for 10days reversed doxorubicin-induced changes in the above mentioned parameters towards the normal values. The present data revealed that doxorubicin exerts its action mainly through the oxidative stress. This appeared from the significant elevation in serum nitric oxide level and cardiac lipid peroxidation level with concomitant decrease in cardiac antioxidative enzymes activity. Treatment with melatonin and its derivatives 3 and 10b could reduce the markers of oxidative stress and restore the activity of the antioxidative enzymes in the heart tissue. In conclusion, the cardioprotective effect of melatonin and its derivatives may be mediated through the antioxidant and free radical scavenging activity of these compounds.     

Genetic variability of the pattern of night melatonin blood levels in relation to coat changes development in rabbits

To assess the genetic variability in both the nocturnal increase pattern of melatonin concentration and photoresponsiveness in coat changes, an experiment on 422 Rex rabbits (from 23 males) raised under a constant light programme from birth was performed. The animals were sampled at 12 weeks of age, according to 4 periods over a year. Blood samples were taken 7 times during the dark phase and up to 1 h after the lighting began. Maturity of the fur was assessed at pelting. Heritability estimates of blood melatonin concentration (0.42, 0.17 and 0.11 at mid-night, 13 and 15 h after lights-out respectively) and strong genetic correlations between fur maturity and melatonin levels at the end of the dark phase (-0.64) indicates that (i) the variability of the nocturnal pattern of melatonin levels is under genetic control and (ii) the duration of the nocturnal melatonin increase is a genetic component of photoresponsiveness in coat changes.     

Effects of melatonin on carbon tetrachloride-induced changes in rat serum

Carbon tetrachloride (CCl4) is a volatile organic chemical, which causes tissue damage, especially to the liver and kidney. In experimental animals it has been shown to be carcinogenic. This study was designed to evaluate the effects of exogenous melatonin administration on the CCl4-induced changes of some biochemical parameters in rat blood. Twenty-four male Wistar rats were randomly divided into three equal groups: Control, CCl4 and CCl4 plus melatonin (CCl4+MEL). Rats in CCl4 group were injected subcutaneously with CCl4 0.5 ml/kg in olive oil while rats in CCl4+MEL group were injected with CCl4 (0.5 ml/kg) plus melatonin (25 mg/kg in 10% ethanol) every other day for one month. Control rats were treated with olive oil. Serum urea, creatinine, total protein, albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total and conjugated bilirubin, alkaline phosphatase (ALP), gamma-glutamyl transferase (gamma-GT), total iron, and magnesium levels were determined. Serum AST, ALT, total and conjugated bilirubin, ALP, gamma-GT, and total iron levels were significantly higher in CCl4-treated rats than in the controls, while urea, total protein, and albumin levels were significantly lower. Melatonin treatment did not cause a significantly change in serum urea, total protein, and albumin levels. However, the elevations in AST, ALT, total and conjugated bilirubin, ALP, gamma-GT, and total iron levels induced by CCl4 injections were significantly reduced by melatonin. On the other hand, melatonin administration significantly decreased serum magnesium levels. These results indicate that melatonin could be a protective agent against the CCl4 toxicity in rats, most likely through its antioxidant and free radical scavenger effects.     

Pineal melatonin: circadian rhythm and variations during the hibernation cycle in the ground squirrel, Spermophilus lateralis

Variations in pineal melatonin content throughout a 24-hour period and during different phases of the hibernation bout cycle were studied in the golden-mantled ground squirrel (Spermophilus lateralis). In addition to pineal melatonin, the circadian variation in the activities of pineal N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) were also investigated in summer animals maintained at 22 +/- 2 degrees C, on a light:dark (L:D) schedule of 12:12 hr for 1 month (lights on at 08.00 hr). Pineal glands were collected from six animals in each group at 1200, 1600, 2000, 2400, 0200, 0400, and 0800 hr. Changes in pineal melatonin content during the hibernation bout cycle were investigated in ground squirrels housed at 4 +/- .05 degrees C in relative darkness (1.9-3.4 lux; 10:14 LD). Pineal glands were obtained between 12:00 and 18:00 hr from 30 animals during one of three phases of the cycle (deep hibernation, euthermic interbout, and entrance into hibernation). Pineal melatonin was also measured for comparison in six winter euthermic animals that were housed at 22 +/- 2 degrees C, on a L:D schedule of 10:14 hr. Melatonin was measured in individual pineal glands by radioimmunoassay. The daily melatonin rhythm in S. lateralis was characterized by a marked increase in pineal melatonin during the dark phase, in which peak nighttime values were nearly 20-fold greater than daytime basal levels. The daily rhythm for NAT activity paralleled the changes in melatonin, showing a peak activity at 0200 hr that was 45 times greater than mean daytime values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Negative correlation of age and the levels of pineal melatonin, pineal N-acetylserotonin, and serum melatonin in male rats

Pineal concentrations of N-acetylserotonin and melatonin and serum levels of melatonin were studied in 3-wk-old (prepubertal), 8-wk-old (adult), and 17-mo-old (senile) male rats. They were adapted to a photoperiod of 12 h light/12 h darkness for a minimum of 1 wk and killed at mid-light and mid-dark. Melatonin and N-acetylserotonin were determined by radioimmunoassay. The concentrations of pineal N-acetylserotonin and melatonin were high in the dark period and low in the light period. Statistical analysis indicated that pineal N-acetylserotonin and melatonin levels per 100 gm body weight declined with age. Similarly, serum melatonin demonstrated diurnal changes in all the age groups studied. In addition, there was a significant reduction in the levels of serum melatonin with age. The parallel patterns of decrease in pineal and serum melatonin levels with age suggest a decline in pineal secretion of melatonin in the older animals.     

Effect of neonatal melatonin administration on sexual development in the rat

In order to study the mechanisms by which melatonin modulates sexual development, 5-day-old female Wistar rats have been treated with a single s.c. injection of melatonin, 3 h before the darkness onset. Criteria for sexual development were the age of vaginal opening and the circulating levels of prolactin, LH, FSH and estradiol. Also, pineal melatonin content was measured. There was a precocious puberty (P less than 0.01) in melatonin-treated rats measured by the age of the vaginal opening. An increase in the number of estrous smears over the whole period studied was observed in melatonin-treated animals as compared to controls. Along with these modifications, there was decrease in pineal melatonin content and serum prolactin levels, on day 21 of life (P less than 0.05), with an increase in both parameters on day 30 of age, in melatonin-treated rats as compared to controls, with no modifications at any other time studied. No differences were detected for serum LH levels considering the whole period studied for both groups. There was a faster decrease in plasma FSH levels with age in melatonin-treated animals than in controls. Serum estradiol levels were decreased in the peripubertal period in melatonin-treated rats as compared to controls. All these data suggest that the modifications induced by neonatal melatonin administration on prolactin, FSH and estradiol could be responsible for the precocious puberty shown in this study.     

Effects of melatonin implants in ram lambs

Sixteen pinealectomized and 19 unoperated ewes were exposed to constant light for about 4 weeks before and 4 weeks after lambing. Six ram lambs born to unoperated ewes were implanted s.c. with melatonin sachets while 8 ram lambs were implanted with empty sachets. The 8 ram lambs born to pinealectomized dams also received empty implants. Ewes and lambs were then returned to the field. Analysis of weekly blood samples indicated that prolactin secretion was significantly decreased in the ram lambs with empty implants between 44-51 weeks of age whereas lambs treated with melatonin failed to show a significant change during development. All 3 groups of rams had elevated LH levels between 7 and 17 weeks of age, and a second period of high LH between 27 and 40 weeks. There were no significant differences between groups in the patterns of FSH secretion; FSH was highest between 7 and 17 weeks of age, and again between 27 and 40 weeks of age. Plasma testosterone levels in all groups increased gradually between 4 and 35 weeks. Between 38 and 48 weeks of age testosterone concentrations were markedly elevated in all groups. Growth was not affected by melatonin treatment. These results indicate that neonatal melatonin treatment has subtle endocrine effects; whether these effects are sufficient to compromise fertility in the ram, however, remains to be established.