Stimulatory Effect Of Melatonin Research Articles

Differentiation of T cells producing interleukin-17 (Th17) against the background of exogenous melatonin during pregnancy.

The population of T lymphocytes producing IL-17 (Th17) plays a dual role during pregnancy and its activity is tightly controlled during this period. One of the factors involved in this process may be the pineal hormone melatonin, which can effectively regulate this T cell population. Here we have shown that exogenous melatonin in pharmacological concentrations is able to enhance the differentiation of Th17 cells of pregnant women in vitro. The stimulatory effects of melatonin were limited to in the first trimester of pregnancy and were apparently mediated by both membrane and nuclear melatonin receptors. Since exogenous melatonin is currently considered as a promising drug in solving various problems associated with reproduction, it is necessary to take into account its immunoregulatory effects.

Melatonin Application Modifies Antioxidant Defense and Induces Endoreplication in Maize Seeds Exposed to Chilling Stress.

The aim of the study was to demonstrate the biostimulating effect of exogenous melatonin (MEL) applied to seeds via hydroconditioning. It was indicated that only well-chosen application technique and MEL dose guarantees success concerning seed germination and young seedlings growth under stress conditions. For maize seed, 50 μM of MEL appeared to be the optimal dose. It improved seed germination and embryonic axes growth especially during chilling stress (5 °C/14 days) and during regeneration after its subsided. Unfortunately, MEL overdosing lowered IAA level in dry seeds and could disrupt the ROS-dependent signal transduction pathways. Very effective antioxidant MEL action was confirmed by low level of protein oxidative damage and smaller quantity of lipid oxidation products in embryonic axes isolated from seeds pre-treated with MEL and then exposed to cold. The stimulatory effects of MEL on antioxidant enzymes: SOD, APX and GSH-PX and on GST-a detoxifying enzyme, was also demonstrated. It was indicated for the first time, that MEL induced defence strategies against stress at the cytological level, as appearing endoreplication in embryonic axes cells even in the seeds germinating under optimal conditions (preventive action), but very intensively in those germinating under chilling stress conditions (intervention action), and after stress removal, to improve regeneration.

Melatonin concentration in peripheral blood and melatonin receptors (MT1 and MT2) in the testis and epididymis of male roe deer during active spermatogenesis

Melatonin regulates male reproductive function in seasonal and non-seasonal breeder mammals. The presence of melatonin membrane receptors (MT1 and MT2) in the testis and epididymis has been demonstrated in several species. Wild roe deer are a short-day breeding species characterised by a short rutting season lasting from mid-July to mid-August. The aim of this study was to determine the concentration of melatonin in the peripheral blood and the presence of MT1 and MT2 receptors in the testis and epididymis in male roe deer during the pre-rut (May), rut (July/August) and post-rut (September) periods. The melatonin concentration was higher in May (522.50 ± 54.20 pg/mL) compared to July/August (258.50 ± 36.82 pg/mL; P < 0.05). During September, the melatonin concentration was higher (393.50 ± 36.77 pg/mL) than in July/August (P < 0.05) but lower than in May (P < 0.05). Immunohistochemical analysis showed the presence of MT1 and MT2 receptors in Leydig cells, Sertoli cells and germ cells in the testis, in addition to the epithelial cells of the epididymis caput, corpus and cauda. MT1 and MT2 receptor expression in the testis and epididymis, assessed by Western blot, was higher in May and July/August (when spermatogenic and steroidogenic activity restarts and reaches its peak, respectively) compared to September (when spermatogenic and steroidogenic activity decreases). This could indicate a stimulatory effect of melatonin on testicular (i.e., steroidogenesis and spermatogenesis) and epididymal (i.e., spermatozoa maturation) function in male roe deer through the MT1 and MT2 receptors. Our results form the basis for further studies into the detailed mechanism of action of melatonin through MT1 and MT2 receptors for optimal reproductive activity in male roe deer and other mammals.

Effect of the melatonin nuclear receptor RORα on monochromatic light-induced T-lymphocyte proliferation in chicken thymus

Present study clarified role of melatonin nuclear receptor RORα in monochromatic light-induced T-lymphocyte proliferation in chicks. Green light elevated plasma melatonin level and organ index, T-lymphocyte proliferation and IL-2 production in thymus, but decreased RORα, p-P65 and p-IκB expressions relative to red light. By contrast, pinealectomy decreased the melatonin content and reversed the stimulatory effect of green light, and resulted in that these thymus parameters were not significantly different among the light-treated groups. Exogenous melatonin supplementation enhanced T-lymphocyte proliferation and IL-2 production in cultured thymocytes. This stimulatory effect of melatonin was reversed by RORα agonist but was enhanced by RORα antagonist. In contrast to RORα antagonist, RORα agonist decreased cytoplasmic P65 level and increased nuclear P65 level. Supplementation with P65 antagonist increased T-lymphocyte proliferation. We conclude that RORα could negatively regulate green light-enhanced T-lymphocyte proliferation in chick thymus by upregulating IκB phosphorylation, which promotes P65 nuclear translocation and NF-κB activation.

Melatonin stimulates the secretion of progesterone along with the expression of cholesterol side-chain cleavage enzyme (P450scc) and steroidogenic acute regulatory protein (StAR) in corpus luteum of pregnant sows

The direct effect of melatonin on porcine luteal function during the pregnancy remains unknown. The objective of the study was to analyse the molecular mechanism(s) by which melatonin directly affects progesterone (P4) production in the corpus luteum (CL) of pregnant sows. We evaluated the localization of melatonin membrane receptors (MT1 and MT2) in CL, and investigated the effect of melatonin on P4 secretion along with the expression of P4 synthesis intermediates in luteal cells. Immunohistochemistry analysis showed that MT1 and MT2 were predominantly localized in luteal cells in pregnant luteal tissues. The results of our in vitro experiments showed that melatonin from 5 to 625 pg/mL was able to significantly increase P4 release (P < 0.05) in a dose-dependent manner. And at the dose of 125 pg/mL treatment, the time-dependent effect on P4 secretion was observed. Furthermore, melatonin from 5 to 625 pg/mL up-regulated both P450scc and StAR expression (P < 0.05) in a dose-dependent manner, and the effect was also time-dependent. No difference of 3β hydroxysteroid dehydrogenase (3β-HSD) expression was observed between control and treatment groups. In addition, melatonin induced a dose- and time-dependent promotion on cell viability. Additionally, the stimulatory effects of melatonin were blocked by luzindole, a non-selective MT1 and MT2 receptor antagonist, or partially blocked by a selective MT2 ligand, 4-phenyl-2-propionamidotetralin (4P-PDOT). The data support the presence of MT1 and MT2 in porcine CL and a regulatory role for melatonin in luteal function through MT1 and MT2-mediated signal transduction pathways.

Effects of melatonin derivatives on human malaria parasite Plasmodium falciparum.

Melatonin's function in modulating the circadian cycle of Plasmodium falciparum has been an intense investigation for the past 45 years. The stimulatory effects of melatonin on malaria growth, development and differentiation have been confirmed by numerous studies conducted in the past 40 years but the molecular mechanisms underlying melatonin stimulatory effects have been well understood recently. Melatonin has been identified as a "signal" essential for synchronization of malaria parasitic cell cycle. Melatonin has been shown to modulate the release of intracellular Ca²⁺ and cAMP in Plasmodium falciparum. In this context, melatonin receptor blocking agent luzindole has been shown to block melatonin's actions in these intracellular events occurring in human malaria parasites. Recent studies have resulted in the synthesis and development of melatonin derivatives, compounds 7-11 and 12-16. Of these compounds 12, 13 and 14 were able to inhibit the Plasmodium falciparum growth and this serves as a promising lead for the development of future antimalarial compounds that will have rapid antimalarial actions with low toxicity. Some antimalarial drugs that have been patented are also summarized in this review.

Melatonin MT1 receptor‐induced transcriptional up‐regulation of p27Kip1 in prostate cancer antiproliferation is mediated via inhibition of constitutively active nuclear factor kappa B (NF‐κB): potential implications on prostate cancer chemoprevention and therapy

Our laboratory has recently demonstrated a melatonin MT1 receptor-mediated antiproliferative signaling mechanism in androgen receptor (AR)-positive prostate epithelial cells which involves up-regulation of p27(Kip1) through dual activation of Gα(s)/protein kinase A (PKA) and Gα(q)/protein kinase C (PKC) in parallel, and down-regulation of activated AR signaling via PKC stimulation. The aim of the present investigation was to identify the transcription factor that mediates melatonin's up-regulatory effect on p27(Kip1) in LNCaP and 22Rv1 prostate cancer cells. Deletion mapping and reporter assays of the p27(Kip1) promoter revealed that the putative melatonin-responsive transcription factor binds to a 116 base-pair region of the promoter sequence, which contains a potential nuclear factor kappa B (NF-κB) binding site. When the NF-κB binding site was abolished by site-directed mutagenesis, the stimulatory effect of melatonin on p27(Kip1) promoter activity was mitigated. Notably, melatonin inhibited the DNA binding of activated NF-κB via MT1 receptor-induced PKA and PKC stimulation. Furthermore, melatonin's up-regulatory effect on p27(Kip1) transcription and consequent cell antiproliferation were abrogated by NF-κB activator but mimicked by NF-κB inhibitor. The results indicate that inhibition of constitutively active NF-κB via melatonin MT1 receptor-induced dual activation of (Gα(s)) PKA and (Gα(q)) PKC can de-repress the p27(Kip1) promoter leading to transcriptional up-regulation of p27(Kip1). MT1 receptor-mediated inhibition of activated NF-κB signaling provides a novel mechanism supporting the use of melatonin in prostate cancer chemoprevention and therapy.

Regulation of leptin synthesis in white adipose tissue of the female fruit bat,Cynopterus sphinx: role of melatonin with or without insulin

Factors regulating leptin synthesis during adipogenesis in wild species are not well known. Studies in the female Cynopterus sphinx bat have shown that it undergoes seasonal changes in its fat deposition and serum leptin and melatonin levels. The aim of the present study was to investigate the hormonal regulation of leptin synthesis by the white adipose tissue during the period of fat deposition in female C. sphinx. This study showed a significant correlation between the seasonal changes in serum melatonin level with the circulating leptin level (r = 0.78; P < 0.05) and with the changes in body fat mass (r = 0.88; P < 0.05) in C. sphinx. A significant correlation between circulating insulin and leptin levels (r = 0.65; P < 0.05) was also found in this species. This in vivo finding suggests that melatonin together with insulin may enhance leptin synthesis by increasing adipose tissue accumulation. The in vitro study showed that melatonin interacts synergistically with insulin in stimulating leptin synthesis by adipose tissue in C. sphinx. The study showed MT(2) receptors in adipose tissue and a stimulatory effect of melatonin on leptin synthesis, which was blocked by treatment with an MT(2) receptor antagonist, suggesting that the effect of melatonin on leptin synthesis by adipose tissue is mediated through the MT(2) receptor in C. sphinx. The in vitro study showed that the synthesis of leptin is directly proportional to the amount of glucose uptake by the adipose tissue. It further showed that melatonin together with insulin synergistically enhanced the leptin synthesis by adipose tissue through phosphorylation of mitogen-activated protein kinase in C. sphinx.

Abnormal proliferation and differentiation of osteoblasts from girls with adolescent idiopathic scoliosis to melatonin

Melatonin deficiency has been postulated as an etiologic factors in adolescent idiopathic scoliosis (AIS). In previous studies, melatonin was shown to regulate skeletal growth and bone formation in both humans and rats. Although it remains controversial whether there are differences in serum melatonin level between AIS and control subjects, melatonin signaling pathway dysfunction in osteoblasts has been reported in patients with AIS. Recently, our group found that melatonin receptor 1B (MT2) gene polymorphism was associated with the occurrence of AIS. Hence, the present study investigated the effect of melatonin on AIS osteoblasts. In vitro assays were performed with osteoblasts isolated from 17 severe AIS girls and nine control subjects. The osteoblasts were exposed to different concentrations of melatonin for 3 days. The effects of melatonin on cell proliferation (as evidenced by MTT assay) and differentiation (demonstrated by alkaline phosphatase activity) were determined. In the control group, melatonin significantly stimulated osteoblasts to proliferate and differentiate. However, in the AIS group, the stimulatory effects of melatonin were not discernible. Importantly, this finding demonstrated that there is a significant difference between AIS and control osteoblasts in functional response toward melatonin. Melatonin-stimulated proliferation of control osteoblasts was inhibited by the MT2 antagonist, 4-phenyl-2-propionamidotetraline, as well as by luzindole, a nonselective melatonin receptor antagonist, suggesting that MT2 is associated with the proliferative action of melatonin. The lack of response in AIS osteoblasts might be because of dysfunction of the melatonin signaling pathway, which may contribute to the low bone mineral density and abnormal skeletal growth observed in patients with AIS.

Melatonin Reduces Nitric Oxide via Increasing Arginase in Rhabdomyolysis-Induced Acute Renal Failure in Rats

Melatonin, the chief secretory product of the pineal gland, is a direct free radical scavenger. In addition to a direct scavenging effect on nitric oxide (NO), its inhibitory effect on nitric oxide synthase (NOS) activity has been also reported. L-arginine is the substrate for both NOS and arginase. It has been suggested that there is a competition between arginase and NOS and that they control each other's level. NO plays a crucial role in the pathogenesis of myoglobinuric acute renal failure (ARF). In this study, the authors aimed to investigate the effect of melatonin on arginase activity, ornithine, and NO levels on the myoglobinuric ARF formed by intramuscular (im) injection of hypertonic glycerol. Forty rats were randomly divided into four groups. Rats in SHAM were given saline, and those in groups ARF, ARF-M5, and ARF-M10 were injected with glycerol (10 mL/kg) im. Concomitant and 24 hours after glycerol injection for the ARF-M5 and ARF-M10 groups, melatonin—5 mg/kg and 10 mg/kg, respectively—was administrated intraperitoneally. Forty-eight hours after the glycerol injection, kidneys of the rats were taken under anesthesia. Arginase activity, ornithine, and NO levels in the kidney tissue were determined. Melatonin had an increasing effect on kidney tissue arginase activities and ornithine levels while decreasing NO concentration. It is possible that besides the direct scavenging effect, the stimulatory effect of melatonin on arginase activity may result in an inhibition of NOS activity and, finally, a decrease in the kidney NO level.

Melatonin and its precursor, L-tryptophan: influence on pancreatic amylase secretion in vivo and in vitro.

Melatonin, considered as a main pineal product, may be also synthetized in the gastrointestinal tract from L-tryptophan. Melatonin has been recently shown to affect insulin release and its receptors have been characterized in the pancreas however, the effects of melatonin on the pancreatic enzyme secretion have not been examined. The aim of this study was to investigate the effects of melatonin or L-tryptophan on amylase secretion in vivo in anaesthetized rats with pancreato-biliary fistulas, and in vitro using isolated pancreatic acini. Melatonin (1, 5 or 25 mg/kg) or L-tryptophan (10, 50 or 250 mg/kg) given to the rats as a intraperitoneal (i.p.) bolus injection produced significant and dose-dependent increases in pancreatic amylase secretion under basal conditions or following stimulation of enzyme secretion by diversion of bile-pancreatic juice. This was accompanied by a dose-dependent rise in melatonin plasma level. Stimulation of pancreatic enzyme secretion caused by melatonin or L-tryptophan was completely abolished by vagotomy, deactivation of sensory nerves with capsaicin or pretreatment with CCK1 receptor antagonists (tarazepide or L-364,718). Pretreatment with luzindole, an antagonist of melatonin MT(2) receptor failed to affect melatonin- or L-tryptophan-induced amylase secretion. Administration of melatonin (1, 5 or 25 mg/kg i.p.) or L-tryptophan (10, 50 or 250 mg/kg i.p.) to the rats resulted in the dose-dependent increase of cholecystokinin (CCK) plasma immunoreactivity. Enzyme secretion from isolated pancreatic acini was not significantly affected by melatonin or L-tryptophan used at doses of 10(-8) -10(-5) M. We conclude that exogenous melatonin, as well as that produced endogenously from L-tryptophan, stimulates pancreatic enzyme secretion in vivo while increasing CCK release. Stimulatory effect of melatonin or L-tryptophan on the exocrine pancreas involves vagal sensory nerves and the CCK release by these substances.

Amikacin-induced acute renal injury in rats: protective role of melatonin.

It is well established that some agents such as aminoglycosides generate free oxygen radicals, leading to an increased oxireductase production, which in turn increases tissue toxicity. The aim of this study is to test whether melatonin, the chief secretory product of the pineal gland and a highly effective antioxidant and free radical scavenger, reduces the nephrotoxicity caused by amikacin (AK). Herein, we investigated the physiologic and pharmacological role of melatonin in influencing AK-induced nephrotoxicity. For this, pinealectomized (Px) and sham operated (non-Px) rats were used. Both AK and melatonin were administered to all groups. We investigated the effects of melatonin on AK-induced changes in levels of malondialdehyde (MDA), a lipid peroxidation product, glutathione (GSH), an antioxidant whose levels are influenced by oxidative stress, and blood urea nitrogen (BUN) and serum creatine (Cr) levels. Morphologic changes in the kidney were also examined by using light microscopy. MDA levels were found to be higher in Px than in non-Px AK-treated animals. Melatonin administration to Px rats reduced MDA levels. In relative to non-Px rats, Px animals treated with AK had significantly lower GSH concentrations while melatonin administration elevated GSH levels in the kidney; however, this stimulatory effect of melatonin was not observed in non-Px AK-treated rats. Treatment with AK alone resulted in significantly higher plasma Cr and BUN levels. Repeated administration of melatonin prevented the AK-induced elevation of plasma Cr and BUN levels. Morphologic damage to renal tubules as a result of AK was more severe in the renal cortex than in the medulla. The damage to the kidney induced by AK was reversed by melatonin in the Px rats. In conclusion, these results show that physiologic melatonin concentrations are important in reducing AK-induced renal damage, while pharmacologic concentrations of melatonin did not add to the beneficial effect.

Effect of exogenous melatonin on neuroendocrine-reproductive function of middle-aged female rats.

The possible role of melatonin in the regulation of the reproductive system of female rats during ageing was investigated in middle-aged female rats showing irregular duration of the oestrous cycle (n = 30). Blood samples were obtained by jugular venepuncture during the oestrous cycle in control rats. After this experiment was completed, the female rats were treated with melatonin for 2 months and blood samples were obtained at different stages of the oestrous cycle. Plasma LH, FSH and prolactin concentrations were significantly increased in the afternoon of the day of pro-oestrus after melatonin treatment compared with control rats. Moreover, FSH concentrations too were significantly increased on the morning of pro-oestrus and oestrus in melatonin treated rats compared with control rats. Similarly, oestradiol concentrations were significantly higher on the morning of pro-oestrus in melatonin treated rats compared with controls. Another group of rats showing irregular duration of the oestrous cycle was used to study the possible effect of melatonin treatment on the timing of pro-oestrous surges of LH and FSH. The results showed that LH and FSH peak values occurred at 5 h after melatonin treatment. Pituitary responsiveness to LHRH in a 90 min test was also studied in middle-aged rats showing irregular duration of the oestrous cycle that had been injected for 1 month with either melatonin or saline. Prolactin response was unaffected by exogenous melatonin, but a stimulatory effect of melatonin on LH and FSH pituitary responsiveness to LHRH was observed. The results indicate an improved function of the neuroendocrine-reproductive axis in middle-aged rats after melatonin treatment.

Stimulatory effect of melatonin on the 5'-monodeiodinase activity in the liver, kidney, and brown adipose tissue during the early neonatal period of the rabbit.

The response of type I 5'-monodeiodinase activity (5'-MD) to a s.c. injection or oral administration of melatonin was studied in 3-, 5-, and 7-day-old rabbits. Melatonin-treated animals showed higher activity of the type I 5'-MD in the liver and kidney and of type II 5'-MD in brown adipose tissue (BAT). This respond to melatonin treatment was age dependent. The stimulatory effect of melatonin on renal 5'-MD activity was observed only in 3- and 5-day-old rabbits and in the liver and BAT during the first week of life. Oral melatonin administration tended to exert a more marked effect on enzyme activity than s.c. injection of the hormone. Changes in 5'-MD activities were accompanied by an increase in serum iodothyronine (T4, T3, and rT3) concentrations. The T3 and rT3 increases may result from the deiodinating processes by the type I 5'-MD and 5-MD, respectively, whereas the rise in the serum T4 was probably due to the stimulatory effect of melatonin on the secretory activity of the thyroid gland itself. These results are the first description of the effects evoked by melatonin treatment during the early neonatal period in newborns of the altricial type.

Melatonin Influences Gonadotropin II Secretion in the Atlantic Croaker (Micropogonias undulatus)

The role of melatonin in the control of gonadotropin II (GtH II) secretion was investigated in Atlantic croaker (Micropogonias undulatus) during different phases of the day–night cycle and seasonal reproductive cycle. Intraperitoneal injection of melatonin during the late-light phase of the day–night cycle elicited a significant elevation in plasma GtH II levels in croaker with fully developed gonads. The increase in GtH II levels was observed 30 min postinjection; the levels remained elevated for 1 hr and started to decline at the 2-hr sampling time. The stimulatory effect of melatonin was dose-dependent over the range 5 to 500 ng/g body weight. Circulating GtH II levels in fish with fully developed gonads showed significant diurnal variation, with elevated levels during the dark phase. The GtH II secretion in response to stimulation by a LHRH analog (LHRHa) also varied during the day–night cycle, with the maximum levels during the early-dark phase. Interestingly, melatonin stimulated GtH II release during the late-light and early- and mid-dark phases. The increased gonadotropic response to melatonin preceded (late-light phase) or corresponded to the period of elevated circulating GtH II levels and increased responsiveness to stimulation by LHRHa during the dark phase, suggesting that melatonin may be involved in the control of daily GtH II cycles in this species. Melatonin inhibited LHRHa-induced GtH II release during the mid-dark phase of the day–night cycle in a dose-dependent manner; the physiological significance of this inhibitory influence is not understood at present. No significant effect of melatonin on basal or LHRHa-induced GtH II release was observed in regressed croaker. Melatonin injection (1 or 10 ng/g body weight) into the third ventricle in the preoptic anterior hypothalamic area (POAH) of croaker with fully developed gonads resulted in an elevation in plasma GtH II concentrations. In addition, a low concentration (0.2 ng/ml) of melatonin stimulatedin vitroGtH II release from the pituitary fragments of fish with fully developed gonads. These results suggest that melatonin can influence GtH II secretion by acting at the level of POAH and also directly at the pituitary to stimulate GtH II release.

Diurnal sensitivity in melatonin-induced hematological changes in the male albino rat.

The influence of melatonin on diurnal changes in the hematological profile was investigated in male albino rats. Following treatment with melatonin, under two different experimental protocols, blood samples were collected at 06.00, 12.00, 18.00 and 24.00 h from separate groups of animals for detailed hematological analysis. In experiment 1, melatonin (25 micrograms, s.c.) treatment, once daily at 17.00 h for 4 weeks, led to an alteration in the rhythm of RBC production with a decrease in its counts at 12.00 h. The total WBC counts were increased at 06.00 and 12.00 h and decreased at 18.00 and 24.00 h. In experiment 2, twice-daily administration of melatonin (once at 09.00 h and again at 17.00 h), for 2 weeks, resulted in a decrease in total RBC counts at 06.00 and 24.00 h, whereas at 18.00 h there was an increase, compared to the respective control values. The total WBC counts increased at 06.00, 12.00 and 18.00 h and decreased at 24.00 h. Erythrocyte indices like mean cell volume (MCV), mean cell hemoglobin (MCH) and mean cell hemoglobin concentration (MCHC), in both experiments, correlated with RBC, hemoglobin and hematocrit values. The WBC differential counts in experiment 1 revealed a decrease in total neutrophils at 24.00 h, whereas in experiment 2 there was a general decrease in their number. While in experiment 1 the total lymphocyte number was increased at 06.00 h and decreased at 18.00 and 24.00 h, in experiment 2 it was increased except at 24.00 h. It may be concluded that melatonin has a modulatory role in hemopoiesis and its rhythms. The stimulatory effect of melatonin on WBC supports its purported immunopotentiating action.

Melatonin specifically stimulates type-II thyroxine 5'-deiodination in brown adipose tissue of Syrian hamsters.

The response of type-II thyroxine 5'-deiodinase (5'-DII) to melatonin treatment was studied in the Syrian hamster. Male hamsters were treated for 15 days with a s.c. pellet containing melatonin, and 5'-DII activity in brown adipose tissue, anterior pituitary gland, Harderian gland and pineal gland was measured using a radioenzymatic technique. Melatonin-treated animals exhibited enhanced 5'-DII activity restricted to brown adipose tissue; the increase was threefold above the values measured in the control group. Serum concentrations of thyroid hormones were unaffected by melatonin treatment. We conclude that the stimulatory effect of melatonin on type-II thyroxine 5'-deiodination is specifically directed to the isoenzyme located in brown adipose tissue and is not accompanied by changes in serum thyroid hormones.

Progonadal role of the pineal in the Djungarian hamster (Phodopus sungorus sungorus): mediation by melatonin.

A progonadal role of the pineal in both adult and juvenile male Djungarian hamsters has been demonstrated which confirms and extends previous reports. In short day-raised hamsters, stimulation of testicular development was achieved by transfer to long days. This stimulatory effect of long days was blocked by pinealectomy. Gonadal stimulation could be elicited in pinealectomized juveniles by timed daily infusions of melatonin. When given for 4 or 6 h daily at a dose rate of 0.83 or 83 ng/h, melatonin infusions stimulated testicular development and body growth. Measurement of plasma FSH and PRL indicated that this pubertal response resulted at least in part from a stimulatory effect of melatonin on the secretion of these hormones. Longer duration infusions (8 or 12 h) did not stimulate testicular development or body growth, and plasma FSH and PRL levels remained low. The efficacy of the short duration infusions did not appear to depend upon the time of day of administration. These findings are in close agreement with those of a previous study which investigated the antigonadal effect of long duration melatonin infusions. The present results demonstrate that melatonin administration can mimic the progonadal effects of the pineal in this species and add further support to the hypothesis that the pineal influences the reproductive system through changes in the duration of daily melatonin production.

Stimulatory effects of melatonin on ependymal epithelium of choroid plexuses in golden hamsters.

Ependymal epithelial cells from the choroid plexuses (CPs) separately of lateral (I + II), IIIrd and IVth ventricles of male Golden Hamsters were studied by electron microscopy and morphometry. The 16 hamsters were distributed between three injections groups: vehicle only, 25 micrograms and 2500 micrograms melatonin (M) by subcutaneous injection daily at L11 to L11.75 in a LD 14:10 daily photoperiod. After 28 consecutive daily injections, animals were killed and the CPs were dissected, fixed and prepared for electronmicroscopy. Thirteen measures of the CP ependymal cells were made, by planimetry, morphometry or direct counting or linear measurement on the EM prints. Effects of melatonin occurred only on the cells from the lateral ventricles. Here M at high dosage caused cell swelling (averaging 50% increase in area), and other cellular changes were graded in relation to M dosage. These were increased (to 26%) in mitochondrial area per cell, and increased (to 50%) in length of apical microvilli. Since in other work the latter form a major locus of ouabain-sensitive Na+, K+-ATPase, it is suggested that M may possibly have a stimulatory effects on transport and related CSF secretory activities by these cells.

Melatonin- and serotonin-stimulated release of vasopressin from rat neurohypophysis in vitro

In order to study the control of vasopressin-release, the effect of a series of potential agents was studied in an in vitro perifusion system of rat neurohypophysis after in vivo treatment with nialamide, a monoamine oxidase inhibitor. In this system, metlatonin stimulated vasopressin-release in a dose-dependent manner (1 × 10 −8 to 1 × 10 −3 M). Serotonin (1 × 10 −3 M) also led to a significant increase of vasopressin-release whereas quipazine (1 × 10 −3 M), a putative serotonin agonist and monoamine oxidase inhibitor, caused a 3-fold stimulation of the release of the neurohormone. The stimulatory effects of melatonin and serotonin were prevented by omission of Ca 2+ combined to an excess of Mg 2+ (12 mM) in the perifusion medium. 1 × 10 −6 M somatostatin did not affect basal or melatonin-stimulated vasopressin-release. These results show that melatonin and serotonin can have a direct stimulatory effect on vasopressin release at the neurohypophyseal level.